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Evaluation of the clinical and allergen specific serum immunoglobulin E responses to oral challenge with cornstarch, corn, soy and a soy hydrolysate diet in dogs with spontaneous food allergy
Veterinary Dermatology
Abstract
Fourteen dogs with known clinical hypersensitivity to soy and corn were maintained on a limited antigen duck and rice diet until cutaneous manifestations of pruritus were minimal (78 days). Sequential oral challenges with cornstarch, corn and soy were then performed. Subsequently, the dogs were fed a diet containing hydrolysed soy protein and cornstarch. Throughout the study period the dogs were examined for cutaneous manifestations of pruritus and, additionally, serum was collected for measurement of allergen-specific and total immunoglobulin (Ig)E concentrations. Intradermal testing with food antigens was performed prior to entry into the study and after 83 days. A statistically significant clinical improvement was measured between days 0 and 83. Significant pruritus was induced after oral challenge with cornstarch, corn and soy (P = 0.04, 0.002, 0.01, respectively) but not with the hydrolysed diet (P = 0.5). The positive predictive value of the skin test for soy and corn allergy was reduced after feeding a soy and corn free diet. Although increases in soy and corn-specific serum IgE concentrations were measured in individual dogs post challenge they were not statistically significant and could not be used to predict clinical hypersensitivity.
... There were six studies [46][47][48][49][50][51] evaluating the effects of hydrolyzed soybean protein on immunologic responses by challenged dogs. The work by [46] demonstrated significant pruritus (itchy skin) after an oral challenge with soybean protein but not with hydrolyzed soybean protein. ...
... There were six studies [46][47][48][49][50][51] evaluating the effects of hydrolyzed soybean protein on immunologic responses by challenged dogs. The work by [46] demonstrated significant pruritus (itchy skin) after an oral challenge with soybean protein but not with hydrolyzed soybean protein. The soybean and corn-specific serum IgE did not increase in dogs post challenge. ...
... To lower adverse food reactions such as food allergies in dogs, soybean meal is often hydrolyzed and used for hypoallergenic prescription diets. The literature shows that hydrolyzed soybean protein leads to significantly fewer allergenic reactions compared to soybean or soybean meal, supporting the supposition that hydrolysis of soybean proteins overcomes these weaknesses of soybean in pet food applications and provides new opportunities [46,[48][49][50]. Further research to compare allergenicity between soybean proteins and other animal proteins would be valuable. ...
Simple Summary
Soybean is a dominant oilseed in the U.S. Although soybeans are valuable ingredients for dogs and cats, soybean use in current pet foods has been low. The research was conducted to answer this question: What effects, if any, do soybean ingredients in dog or cat diets have on animal health and nutrition, palatability, feeding behavior, allergenicity, and extrusion processing? We summarized the most current research on soybeans in pet foods published since 2000. We discussed the strengths, weaknesses, opportunities, and threats of soybean in pet food applications. We concluded that various food processing technologies and the versatility of soybean ingredients have been demonstrated to offer considerable potential for inclusion as oil, protein, fiber, or functional ingredients in pet foods. Our work will be valuable, providing research status and gaps.
Abstract
Soybean use has been low in pet foods, even though they are an excellent source of protein, polyunsaturated fatty acids, and gut fermentable fibers. The purpose of this evaluation was to conduct a systematic review of the public literature to explore how soybeans have been researched for pet food applications since 2000 and to provide strengths, weaknesses, opportunities, and threats for soybeans in the pet food industry. The review covered a total of 44 articles related to soybean ingredients and their potential value in the pet food arena. The articles were categorized by their research contents and narratively summarized to demonstrate useful information to both the pet and soybean industries. When soybean-based products have been adequately processed to reduce the antinutritive factors, they are comparable to processed animal proteins in nutritional value, palatability, and functionality in pet food processing. We conclude that various food processing technologies and the versatility of soybean ingredients allow soybean to have considerable inclusion potential in pet foods. More research on dietary soybean ingredients regarding pet food processing, fermentation benefits on health, and consumer acceptance will be needed to understand soybean’s position in the future pet food industry.
... For the purpose of this study, we considered OFCs made both with the original diet and its composing ingredients. Thus, we selected nine [8][9][10][11][12][13][14][15][16] and two [17,18] papers relevant to dogs and cats with FAs, respectively. After scanning the bibliography of these articles and those of the previously published critically-appraised topics on CAFRs of companion animals [1][2][3][4][5][6][7], we identified three additional papers [19][20][21]. ...
... Ultimately, the total number of articles selected was 13 of whom 11 were large case series or clinical trials [8-13, 15-18, 20] and the other two were case reports of one animal each [19,21]. All but two studies involved dogs and cats with spontaneously-arising FAs occurring in a natural home environment, the last two were from dogs with spontaneous FAs who lived in a university-based laboratory animal facility [11,13]. ...
... The patients included in the studies had a worldwide distribution, as five articles reported data from pets seen in the USA [9,11,13,17,19] two articles contained cases from the United Kingdom [10,15] and France [8,20] and there was one article from the Netherlands [12], Japan [21] and Australia [18]. The last paper included dogs from Switzerland and the USA [16]. ...
Background:
At this time, elimination diets followed by oral food challenges (OFCs) represent the "gold standard" for diagnosing skin-manifesting food allergies (FA) in dogs and cats. Regrettably, there is no clear consensus on how long one should wait for clinical signs to flare after an OFC before diagnosing or ruling-out a FA in a dog or a cat.
Results:
We searched two databases on October 23, 2019 to look for specific information on the time for a flare of clinical signs to occur during OFCs after elimination diets in dogs and cats with skin-manifesting FAs. Altogether, we reviewed the study results of nine papers that included 234 dogs and four articles containing data from 83 cats. As multiple OFCs could be done in the same patient and not all animals included were subjected to an OFC, we were able to compile 315 and 72 times to flare (TTF) after an OFC in dogs and cats, respectively. When regrouping all cases together, about 9% of dogs and 27% of cats exhibited a flare of clinical signs in the first day after an OFC; 21% of dogs and 29% of cats had such relapse by the end of the second day. The time needed for 50 and 90% of dogs to exhibit a deterioration of clinical signs (TTF50 and TTF90) was 5 and 14, respectively; in cats, these times were 4 and 7 days, respectively. By 14 days after an OFC, nearly all food-allergic patients from both species had had a relapse of clinical signs. These results are limited by the likely under-reporting of flares that occur on the first day immediately following an OFC, the time in which IgE-mediated acute allergic reactions typically develop.
Conclusion:
Veterinary clinicians performing an OFC need to wait for 14 and 7 days for more than 90% of dogs and cats with a skin-manifesting FA to have a flare of clinical signs, respectively.
... Bij het hydrolyseren ontstaan immers kleinere deeltjes en de immunoglobulinen E die zich op de mastcellen bevinden, kunnen op deze sterk verkleinde proteïnen niet binden, waardoor er geen allergische reactie ontstaat (Olivry en Bizikova, 2010). Dit heeft tot gevolg dat ook de klinische symptomen van allergie kunnen worden gereduceerd (Jackson et al., 2003;Ricci et al., 2010). ...
... Net als voor de diagnosestelling kan ook voor het management van voedselallergie een dieet worden gegeven gebaseerd op een gehydrolyseerde eiwitbron. In verschillende studies bleek dit effectief te zijn (Marks et al., 2002;Jackson et al., 2003;Loeffler et al., 2006;Puigdemont et al., 2006;Mandigers et al., 2010;Ricci et al., 2010, Cave, 2012. In deze studies kon echter vaak niet achterhaald worden op welk specifiek allergeen de honden allergisch reageerden. ...
... Om met stelligheid te kunnen oordelen of het dieet op basis van hydrolysaten al dan niet werkt, moeten de honden vooraf correct geselecteerd worden: honden allergisch voor soja moeten getest worden met sojahydrolysaten en dieren die allergie vertonen voor kip mogen enkel getest worden met kiphydrolysaten. Er zijn slechts weinig studies in de literatuur te vinden waarin met die selectie rekening gehouden wordt (Jackson et al., 2003;Puigdemont et al., 2006;Ricci et al., 2010). Vaker werd het bovenstaande principe niet toegepast (Marks et al., 2002;Loeffler et al., 2006;Mandigers et al., 2010). ...
Voedselallergie is een veel voorkomend probleem, zowel bij huisdieren als bij de mens. Zo wordt in de diergeneeskunde vaak voedselallergie vastgesteld bij de hond. Verschillende allergenen, zoals vlees, eieren en melk, worden aangeduid als boosdoener bij de hond en soms wordt er kruisreactiviteit gezien tussen verschillende allergenen. Bij de mens zijn vooral pinda’s, noten en koemelk bekend als veelvoorkomende antigenen. De symptomen variëren zowel bij de hond als bij de mens van huidklachten tot gastro-intestinale symptomen. De diagnosestelling van voedselallergie bij de hond gebeurt het beste door middel van een testdieet, bestaande uit twee fasen: de eliminatie- en provocatiefase. Andere testen, zoals de intradermale huidtest, serologie, de basofieldegranulatietest en gastroscopische voedselovergevoeligheidstest zijn ook beschikbaar. Echter, deze testen geven vaak weinig betrouwbare resultaten. De behandeling van voedselallergie berust in de eerste plaats op de eliminatie van het allergeen in de voeding. Dit kan eventueel worden aangevuld met medicatie, zoals corticosteroïden en antihistaminica.
... These results are not surprising, as they echo the clinical indings of experimental challenges in corn-sensitized dogs [11]. In this study, 14 Maltese-beagle atopic dogs with historical clinical hypersensitivity to corn and soy were challenged, in three separate phases of two consecutive administration days, with 200 mg/kg of cornmeal (i.e., kernels ground to a coarser texture than flour), cornstarch and soy [11]. ...
... These results are not surprising, as they echo the clinical indings of experimental challenges in corn-sensitized dogs [11]. In this study, 14 Maltese-beagle atopic dogs with historical clinical hypersensitivity to corn and soy were challenged, in three separate phases of two consecutive administration days, with 200 mg/kg of cornmeal (i.e., kernels ground to a coarser texture than flour), cornstarch and soy [11]. While ten of these 14 dogs (71%) exhibited a flare of clinical signs after eating the cornmeal, only three (21%) flared with cornstarch, these three dogs also having reacted to cornmeal. ...
... Consequently, only three of ten dogs Anallergenic corn starch extract 0% 0% 0% 0% Fig. 1 Frequencies of sera with positive reactions to the various extracts. a canine sera; b feline sera (30%) clinically-reactive to cornmeal had a flare after eating the cornstarch [11]. Even though cornstarch contains approximately less than one-twentieth of the protein amount of corn flour (0.3 vs 6.9 g of protein/100 g; http://nutritiondata.self.com; ...
Background
Corn appears to be an uncommon food source of allergens in dogs and cats. There is limited information on the nature of the corn allergens in dogs and cats and their presence in the various foodstuffs used in commercial pet foods. The aim of this study was to determine if serum IgE from corn-sensitized dogs and cats recognized proteins in corn flour and cornstarch, which are common sources of carbohydrates in pet foods. ResultsWe selected archived sera from allergy-suspected dogs (40) and cats (40) with either undetectable, low, medium or high serum levels of corn-specific IgE. These sera were tested then by ELISA on plates coated with extracts made from corn kernels, corn flour, cornstarch and the starch used in the commercially-available extensively-hydrolyzed pet food Anallergenic (Royal Canin). Immunoblotting was then performed on the same extracts with some of the sera from moderate-to-high corn-sensitized dogs and cats. Using ELISA, it is mostly the dogs and cats with moderate and high corn-specific IgE levels that also had IgE identifying allergens in the flour (dogs: 20/30 sera, 67% - cats: 20/29, 69%). In contrast, none of the tested sera had measurable IgE against proteins isolated from the cornstarch. Immunoblotting confirmed the existence of numerous major corn allergens in the corn kernel extract, fewer in that of the corn flour, while such allergens were not detectable using this technique in the two cornstarch extracts. Conclusions
In this study, ELISA and immunoblotting results suggest that IgE from corn-sensitized dogs are less likely to recognize allergens in cornstarch than in kernel and flour extracts. As corn is not a common allergen source in dogs and cats, and as its starch seems to be less allergenic than its flour, pet foods containing cornstarch as a carbohydrate source are preferable for dogs and cats suspected of suffering from corn allergy.
... Bovine immunoglobulin G (IgG) was found to be the common allergen in cow's milk, and a specific phosphoglucomutase and heavy chain IgG were the responsible allergens in extracts of both lamb and beef [13]. Another study examined 14 dogs with clinical hypersensitivity to soy and corn [14]. Minimal clinical signs of pruritus were seen once they were fed a limited antigen diet of duck and rice. ...
... Minimal clinical signs of pruritus were seen once they were fed a limited antigen diet of duck and rice. Following sequential re-challenge with cornstarch, corn, soy and a hydrolyseddiet, however, significant pruritus returned with cornstarch, corn and soy but not with the hydrolysed diet [14]. A later study from 2016, found the most commonly encountered food allergens in dogs were beef, dairy products, chicken and wheat. ...
... Open Access Collectively, these results provide a plausible explanation of why pets with suspected or even proven adverse food reactions may fail to respond to commercial limited antigen source foods [6,14,17]. Lastly, the data summarized above are further confounded by the fact that many pets also receive a variety of supplements, preventive pharmaceuticals such as those for heartworm, flea and tick exposures, as well as puppy and periodic booster vaccines. ...
... As similar standards are not currently applied to hydrolyzed pet foods, the proteins in these diets may still retain their antigenic potential. This was demonstrated in one study, which indicated that a significant proportion (21%) of dogs sensitized to the intact protein still reacted adversely to the hydrolyzed diet [6]. Therefore, the most significant clinical problem with veterinary hydrolyzed diets may be the retention of antigenicity leading to continued clinical signs. ...
... Ten grams of each dry food (the basal diet and each of the 3 hydrolyzed diets) 2,3,4,5 collected from a new unopened bag was ground with sterile water using a clean pestle and mortar. The mixture was then transferred to a 50 ml sterile tube 6 and incubated overnight at 4-degrees on a rotator. The tube was centrifuged at 8000 rpm for 1 minute at room temperature and the supernatant was filtered using a 0.22-μm polyethersulfone sterile filter 7 in a sterile tissue culture hood. ...
... This may suggest that if an animal was allergic to chicken or soy, then they may be able to recognize and react to the hydrolyzed forms of these proteins. This has been shown in one study, where 21% of dogs sensitized to the intact protein still reacted adversely to the hydrolyzed diet [6]. One possible cause for the persistence of clinical signs could be due to retention of larger sized or intact proteins in the hydrolyzed diet. ...
Background:
Hydrolyzed diets are used in companion animals for the diagnosis and treatment of adverse food reaction. Similarly, hydrolyzed formulas are used in human infants with severe inflammatory bowel disease or milk allergy, and these must meet the standard of hypoallergenicity through rigorous testing. Unfortunately, no standards are currently applied to hydrolyzed veterinary therapeutic diets, and data for the immunogenicity of feline diets is also not available. Therefore, the main aim of this pilot study was to determine if ex-vivo whole blood stimulation assays could be used to characterize the cytokine response to hydrolyzed commercial diets in a small number of individual healthy immunotolerant cats. This approach has also been used to investigate cytokine production in response to cow milk protein in humans and currently similar studies do not exist in companion animals. Nine healthy cats previously eating the same basal diet were divided into groups and fed one of three hydrolyzed diets exclusively for 6 weeks. Heparinized whole blood was collected from each cat before and after the feeding trial. Ex-vivo whole blood stimulation assays were performed using crude extracts of the basal diet as a positive control, as this diet contained the same proteins present in the hydrolyzed diet but were intact, saline as a negative control, and each cat's respective hydrolyzed diet. Supernatants were collected and analyzed for tumor necrosis factor-alpha, interleukin-10 (IL-10), and interleukin-4 using enzyme-linked immunosorbant assay.
Results:
Seven cats produced detectable amounts of the anti-inflammatory cytokine IL-10 upon stimulation with the basal diet. Two cats produced detectable amounts of IL-10 upon stimulation with a hydrolyzed soy-based diet and one cat produced a detectable amount of IL-10 upon stimulation with a hydrolyzed chicken-based diet (>125 pg/mL).
Conclusions:
Results from this pilot study suggest that in some healthy immunotolerant cats, some hydrolyzed diets may elicit a similar cytokine response compared to their basal diet, which contained the same proteins intact. Therefore, animals may be able to recognize and react to some hydrolyzed forms of tolerated proteins, and may also suggest IL-10 as a target for investigation as a potential marker for dietary tolerance in cats, however further studies would be necessary to corroborate this. Further studies are also needed to determine if this would also be the same in immunologically naïve, sensitized and clinically hypersensitized cats.
... Altogether, we selected 23 papers [1,[3][4][5][6][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25] and one abstract from conference proceedings [26] that reported results of various laboratory tests in dogs or cats where an AFR was definitely diagnosed or ruled-out. We excluded studies where the diagnosis of AFR was not confirmed or the results of the individual laboratory tests could not be attributed to a specific patient. ...
... We excluded studies where the diagnosis of AFR was not confirmed or the results of the individual laboratory tests could not be attributed to a specific patient. The chosen publications were mostly case-control studies, and there were two case series [11,12] and one each a single case report [10] and a prospective cohort study [13]. In all, there were twelve studies testing foodspecific IgE in the serum of dogs [1, 5, 6, 9, 10, 12-14, 16, 18, 23, 24] and three in cats [15,17,21]. ...
... Lymphocyte proliferation tests were assessed in four studies in dogs [11,14,18,20] and one in cats [15]. In dogs, intradermal testing and gastroscopic food testing were reported in six [3,4,9,10,13,14] and three studies [8,19,28] respectively. There were two studies for patch testing in dogs [5,25], and one study each for gastroscopic food testing in cats [17], colonoscopic testing in dogs [22], determination of canine fecal IgE [8] and hair and saliva testing in dogs [26]. ...
Background
The gold standard to diagnose adverse food reactions (AFRs) in the dog and cat is currently an elimination diet with subsequent provocation trials. However, those trials are inconvenient and client compliance can be low. Our objective was to systematically review the literature to evaluate in vivo and in vitro tests used to diagnose AFR in small animals. ResultsWe searched three databases (CAB Abstracts, MEDLINE and Web of Science) for pertinent references on September 16, 2016. Among 71, 544 and 41 articles found in the CAB Abstract, MEDLINE and Web of Science databases, respectively, we selected 22 articles and abstracts from conference proceedings that reported data usable for evaluation of tests for AFR. Serum tests for food-specific IgE and IgG, intradermal testing with food antigens, lymphocyte proliferation tests, fecal food-specific IgE, patch, gastroscopic, and colonoscopic testing were evaluated. Conclusions
Testing for serum food-specific IgE and IgG showed low repeatability and, in dogs, a highly variable accuracy. In cats, the accuracy of testing for food-specific IgE was low. Lymphocyte proliferation tests were more frequently positive and more accurate in animals with AFR, but, as they are more difficult to perform, they remain currently a research tool. All other reported tests were only evaluated by individual studies with small numbers of animals. Negative patch test reactions have a very high negative predictability in dogs and could enable a choice of ingredients for the elimination diet in selected patients. Gastroscopic and colonoscopic testing as well as food-specific fecal IgE or food-specific serum IgG measurements appear less useful. Currently, the best diagnostic procedure to identify AFRs in small animals remains an elimination diet with subsequent provocation trials.
... Bij het hydrolyseren ontstaan immers kleinere deeltjes en de immunoglobulinen E die zich op de mastcellen bevinden, kunnen op deze sterk verkleinde proteïnen niet binden, waardoor er geen allergische reactie ontstaat (Olivry en Bizikova, 2010). Dit heeft tot gevolg dat ook de klinische symptomen van allergie kunnen worden gereduceerd (Jackson et al., 2003;Ricci et al., 2010). ...
... Net als voor de diagnosestelling kan ook voor het management van voedselallergie een dieet worden gegeven gebaseerd op een gehydrolyseerde eiwitbron. In verschillende studies bleek dit effectief te zijn (Marks et al., 2002;Jackson et al., 2003;Loeffler et al., 2006;Puigdemont et al., 2006;Mandigers et al., 2010;Ricci et al., 2010, Cave, 2012. In deze studies kon echter vaak niet achterhaald worden op welk specifiek allergeen de honden allergisch reageerden. ...
... Om met stelligheid te kunnen oordelen of het dieet op basis van hydrolysaten al dan niet werkt, moeten de honden vooraf correct geselecteerd worden: honden allergisch voor soja moeten getest worden met sojahydrolysaten en dieren die allergie vertonen voor kip mogen enkel getest worden met kiphydrolysaten. Er zijn slechts weinig studies in de literatuur te vinden waarin met die selectie rekening gehouden wordt (Jackson et al., 2003;Puigdemont et al., 2006;Ricci et al., 2010). Vaker werd het bovenstaande principe niet toegepast (Marks et al., 2002;Loeffler et al., 2006;Mandigers et al., 2010). ...
Food allergy is a common problem in both pets and humans. In veterinary medicine, food allergy is frequently diagnosed in dogs. Various food components, such as meat, eggs and milk, are described as allergens in dogs, and cross-reactivity is often seen between different allergens. In humans, peanuts, tree nuts and cow's milk are known as most common antigens. Symptoms vary in both dogs and humans from skin problems to gastrointestinal symptoms. The best way to diagnose food allergy in dogs is by means of a test diet, consisting of two phases: elimination and provocation. Other tests, such as the intradermal skin test, serology, the basophil degranulation test and gastroscopic food sensitivity test are also available. However, these tests often give unreliable results. The treatment of food allergy is based on the elimination of the allergen in the diet. This may optionally be supplemented by the administration of drugs, such as corticosteroids and antihistamines.
... Some of these include digestive issues, itching and red patches on skin. Undesirable and worst reactions to food include a diversity of immunological, toxicological, or metabolic causes [4]. From the list of eight food allergens peanut, wheat and soy allergens are considered as major allergen and very small amounts of these allergens can induce severe allergic reaction that persists throughout life. ...
... Melt curve analysis shows peak of Arah1, soy 28k and triglutenin in the positive samples of soybean, peanut and wheat (Figs. [3][4][5]. Because of T m that was 53 • C, we identified each allergen and further confirmed through gel based analysis of real-time PCR product that produced distinguish bands of 162bp, 85bp and 82bp, respectively [12,13] (Fig. 6). ...
... The most common food sources of allergens are also shared between dogs and allergic people, such as beef, dairy, wheat, lamb, egg, chicken, soy, oats, and pork. In addition, dogs and humans have similar gastrointestinal tract anatomy and physiology, as well as nutritional requirements [7]. However, even dogs with high levels of IgE are not easy to identify by ELISA and immunoblot experiments, due to intrinsically higher levels of IgG antibody class compared to humans, probably caused by a high parasitic load [8]. ...
... The advantages of using sheep as animal models of food allergy are their similar size and physiology to humans, as well as calm nature, and fewer ethical restrictions compared to the use of other large animal models [21]. There are three well-characterized canine models of food allergy from which researchers have drawn several conclusions [7,22]. The most important outcome of studies performed on dog food allergy models is the hypothesis that genetically predisposed individuals that suffer from early gut infections are prone to respond to bystander antigens more aggressively compared to healthy individuals. ...
Food hypersensitivity reactions are adverse reactions to harmless dietary substances, whose causes are hidden within derangements of the complex immune machinery of humans and mammals. Until recently, enterocytes were considered as solely absorptive cells providing a physical barrier for unwanted lumen constituents. This review focuses on the enterocytes, which are the hub for innate and adaptive immune reactions. Furthermore, the ambiguous nature of enterocytes is also reflected in the fact that enterocytes can be considered as antigen-presenting cells since they constitutively express major histocompatibility complex (MHC) class II molecules. Taken together, it becomes clear that enterocytes have an immense role in maintaining oral tolerance to foreign antigens. In general, the immune system and its mechanisms underlying food hypersensitivity are still unknown and the involvement of components belonging to other anatomical systems, such as enterocytes, in these mechanisms make their elucidation even more difficult. The findings from studies with animal models provide us with valuable information about allergic mechanisms in the animal world, while on the other hand, these models are used to extrapolate results to the pathological conditions occurring in humans. There is a constant need for studies that deal with this topic and can overcome the glitches related to ethics in working with animals.
... Diet trial failures with hydrolysed diets may be due to a predominantly T-cellmediated immune response or presence of a subset of proteins in the diet insufficiently hydrolysed to prevent an IgE-mediated reaction. [2][3][4][5] Other problems include possible cross-reactivity of the novel protein source with common allergens and questionable sustainability and unreliable availability of the protein source. 6 Additionally, some of these diets contain soy as a listed ingredient, which is a potential allergen. ...
... 6 Additionally, some of these diets contain soy as a listed ingredient, which is a potential allergen. 3,7 There are also reports that these diets can contain one or more undeclared animal proteins that could elicit an allergic reaction in a patient allergic to those proteins. [8][9][10][11] A prescription vegetarian diet utilizing oat groats, brewer's rice and potato protein is available, effectively alleviating concerns of sustainability and cross-reactivity with common allergens, but is not marketed specifically for diet trials. ...
Background:
Cutaneous adverse food reaction (CAFR) is diagnosed by performing an elimination diet trial utilizing prescription or home-cooked diets followed by provocative challenge.
Objectives:
To report findings of PCR analysis of a prescription vegetarian diet (RCV) for undeclared proteins of animal origin, as well as to describe its utilization for diagnosis and management of dogs suspected of having CAFR.
Animals:
Three client-owned dogs.
Methods:
PCR analysis of RCV for 11 mammalian species and poultry. In three dogs, clinical examination, cytology, aerobic culture (if indicated) and at least one elimination diet trial with RCV.
Results:
In our case series, all dogs had a history of pruritus and recurrent pyoderma that resolved with infection control and an elimination diet trial. In cases 1 and 2, a diagnosis of CAFR was made following an elimination trial with RCV and provocative challenge. Case 3 had a previously confirmed diagnosis of CAFR and RCV was successfully used to maintain remission of CAFR-related signs. PCR testing of RCV was negative for 11 mammalian species and poultry.
Conclusions and clinical importance:
The RCV diet was found not to contain any undeclared mammalian or avian proteins. In this case series, the RCV was successfully used to diagnose and maintain three dogs with CAFR.
... Comercialmente se encuentran disponibles dietas que se componen de una sola fuente de proteína animal como carne de venado, pato, conejo y canguro, y una fuente de carbohidratos, tales como papa y la avena. Las dietas hidrolizadas se consideran como realmente hipoalergénicas 22,23 (perros sensibles a la soya, no desarrollan una reacción a la soya hidrolizada también se ha encontrado que dietas parcialmente hidrolizadas no son tan efectivas y los pacientes con estas dietas podrían empeorar los signos clínicos 22,23 . Cada vez es más frecuente el uso de dietas hidrolizadas para el diagnóstico de RAA en perros y gatos, especialmente porque las dietas que contienen hidrolizado de hígado de pollo, caseína, o soya están disponibles comercialmente. ...
... Comercialmente se encuentran disponibles dietas que se componen de una sola fuente de proteína animal como carne de venado, pato, conejo y canguro, y una fuente de carbohidratos, tales como papa y la avena. Las dietas hidrolizadas se consideran como realmente hipoalergénicas 22,23 (perros sensibles a la soya, no desarrollan una reacción a la soya hidrolizada también se ha encontrado que dietas parcialmente hidrolizadas no son tan efectivas y los pacientes con estas dietas podrían empeorar los signos clínicos 22,23 . Cada vez es más frecuente el uso de dietas hidrolizadas para el diagnóstico de RAA en perros y gatos, especialmente porque las dietas que contienen hidrolizado de hígado de pollo, caseína, o soya están disponibles comercialmente. ...
The skin pathologies of nutritional origin either due to alterations in intestinal absorption of some nutrients or genetic predispositions affecting its absorption; nutritional deficiencies may occur by poor development of both home and commercial diets; although at present are not as common for the regulation of food is balanced and demands by control agencies in each country. These conditions are related to some vitamins such as A, D, E and C, essential fatty acids, proteins, and certain minerals such as zinc. Among dermatological diseases and clinical signs include food allergies, dry and oily seborrhea, scaling, follicular plugging, hair loss and dull, dry coat, among others. The aim of this review is closer to the vet to the causes of dermatologic disease of nutritional origin clinical, since alterations of the skin in general are very common in the veterinary clinic for small animals and we need to recognize all the pathologies and treat appropriately
... Consequently, hydrolysed proteins result less allergenic and more digestible (S a et al. 2013). In this regard, in a study by Jackson et al. (2003), the majority of dogs with confirmed adverse reactions to soy and corn did not show a flare-up of their skin disease when fed a soy hydrolysate and corn starch diet. Differences in the degree of hydrolysation and protein source can influence the clinical response as shown in experimentally sensitised dogs (Olson et al. 2000). ...
... Nowadays, the market of industrial food for pets, especially for those with a suspect or a confirmed diagnosis of AFRs, is currently growing. In this regard, protein hydrolysates have demonstrated to be particularly hypoallergenic, as their employment has shown to treat efficaciously food allergies even deriving from the corresponding whole protein source (Jackson et al. 2003). The employment of European rapeseed and sunflower DSM (derived from the biodiesel production chain and characterised by a high protein content), easily useful and broadly available, could represent a valid alternative to this problem, reducing the costs. ...
The digestibility (in vitro), toxicity and metabolic effects of rapeseed (RPH) and sunflower (SPH) protein hydrolysates have been evaluated in a murine animal model. The enzyme Alcalase® was employed to obtain a mild enzymatic hydrolysis of rapeseed and sunflower defatted seed meals (DSM) protein isolates. Both hydrolysates showed higher in vitro digestibility than the respective DSM, presumably as a consequence of the hydrolysis process that they had undergone. In vivo, RPH and SPH were well tolerated. Body and organ weights, biochemical blood parameters from treated male mice were comparable to controls. Food intake was regular in RPH and SPH animals, suggesting a good palatability of the hydrolysates. Not relevant perturbations of the principal hepatic and renal drug metabolism enzymes were observed in RPH or SPH mice. In conclusion, protein hydrolysates from sunflower and rapeseed DSM did not determine relevant toxicological effects; therefore, they could be considered as alternative protein sources and/or food ingredients.
... Comercialmente se encuentran disponibles dietas que se componen de una sola fuente de proteína animal como carne de venado, pato, conejo y canguro, y una fuente de carbohidratos, tales como papa y la avena. Las dietas hidrolizadas se consideran como realmente hipoalergénicas 22,23 (perros sensibles a la soya, no desarrollan una reacción a la soya hidrolizada también se ha encontrado que dietas parcialmente hidrolizadas no son tan efectivas y los pacientes con estas dietas podrían empeorar los signos clínicos 22,23 . Cada vez es más frecuente el uso de dietas hidrolizadas para el diagnóstico de RAA en perros y gatos, especialmente porque las dietas que contienen hidrolizado de hígado de pollo, caseína, o soya están disponibles comercialmente. ...
... Comercialmente se encuentran disponibles dietas que se componen de una sola fuente de proteína animal como carne de venado, pato, conejo y canguro, y una fuente de carbohidratos, tales como papa y la avena. Las dietas hidrolizadas se consideran como realmente hipoalergénicas 22,23 (perros sensibles a la soya, no desarrollan una reacción a la soya hidrolizada también se ha encontrado que dietas parcialmente hidrolizadas no son tan efectivas y los pacientes con estas dietas podrían empeorar los signos clínicos 22,23 . Cada vez es más frecuente el uso de dietas hidrolizadas para el diagnóstico de RAA en perros y gatos, especialmente porque las dietas que contienen hidrolizado de hígado de pollo, caseína, o soya están disponibles comercialmente. ...
... Serological tests involving the measurement of specific IgG and IgE antibodies in serum with western blot have not yet been clinically validated for diagnostics due to its low sensitivity (Mueller and Tsohalis 1998, Foster et al. 2003, Jackson et al. 2003, Martin et al. 2004, Ricci et al. 2010, Zimmer et al. 2011, Bethlehem et al. 2012Favrot et al. 2017). Limited research on serological tests has been performed in cats and, similarly to dogs, it is believed that the concentration of specific antibodies is not reliable in the diagnosis of food allergies. ...
Cutaneous adverse food reaction (CAFR) is a common disease, affecting about 1-2% of dogs and cats. Diagnosis of the CAFR is made through elimination diet coupled with diet challenge, as methods like skin tests, patch tests, basophil degranulation tests and assessment of IgG and IgE serum levels are not sensitive enough. A partially hydrolysed salmon and pea hypoallergenic diet was evaluated in the diagnosis and treatment of CAFR in dogs and cats. The diet was used in the treatment of 13 dogs and 12 cats for 10 weeks. The Pruritus Visual Analog Scale (PVAS; dogs and cats), Canine Atopic Dermatitis Extent and Severity Index (CADESI-04; dogs) and the Scoring Feline Allergic Dermatitis (SCORFAD; cats) were used for effectiveness evaluation. In dogs, a significant decrease was reported in both CADESI-04 (from 17.3±7.5 to 10.15±7.4; p=0.028) and PVAS (from 7±1.3 to 4.76±1.8; p=0.003) after four weeks of treatment. Also in cats, both the PVAS (from 6.75±1.8 to 4±2.3; p=0.006) and SCORFAD (from 4.16±1.9 to 2.58±1.2; p=0.029) decreased significantly after four weeks. After eight weeks, a significant improvement was observed in almost all the animals. Evaluated diet was useful in the treatment of the CAFR in dogs and cats.
... Immunotherapy doesn't take a shot by any stretch of the imagination. Cost is likewise an issue in a portion of the cases [7][8][9][10][11][12][13][14][15]. When reading this table we are interested in the results of the "Pearson Chi-Square" row. ...
... Adverse food reactions should always be with pruritic, unilateral or bilateral otitis externa, it may accompanied by secondary bacterial or Malassezia infections [10] . Other presentations of food allergy include recurrent superficial pyoderma, pruritic papular eruptions over the trunk and head [2] .Adverse food reactions concurrent to flea-allergic or atopic dermatitis accounting for 20% to 30% or more of dogs has been documented [22] . Concurrent GIT signs (vomiting, diarrhea, frequent defecation, colitis etc) were seen to occur in 10-15% dogs with skin infections caused by an adverse reaction to food [23] . ...
... Allergic diseases in canines include atopic dermatitis, gastroenteric in ammation, and anaphylaxis [15,16]. Owing to the numerous similarities between canine and human atopic dermatitis [17], atopic dogs have served as animal models for food allergies to cow's milk [11], corn [18], and nuts [12]. ...
Background: IgE reactivity to fish allergens in atopic dogs, which are used as models for food allergy, has not been elucidated to date. We investigated IgE reactivity to crude extracts and purified allergens derived from the Pacific cod (Gadus macrocephalus) in atopic dogs to identify the allergenic proteins of cod.
Results: The levels of specific IgE to crude cod extracts were measured in the sera of 179 atopic dogs, including 27 dogs with cod allergy, using enzyme-linked immunosorbent assay (ELISA). Specific IgE to crude cod extracts were present in 36 (20%) of the 179 atopic dogs and in 12 (44%) of the 27 dogs with cod allergy. The allergens in crude cod extracts were analyzed by ELISA, immunoblotting, and liquid chromatography-tandem mass spectrometry. In allergen component analysis, IgE reactivity to tropomyosin and enolase was observed in the sera of dogs with cod allergy. IgE reactivity to parvalbumin, collagen, and tropomyosin was evaluated using the sera of atopic dogs that tested positive for specific IgE to crude cod extracts. Among the 36 dogs with IgE reactivity to crude cod extracts, 9 (25%), 14 (39%), and 18 (50%) dogs tested positive for specific IgE to parvalbumin, collagen, and tropomyosin, respectively.
Conclusions: The IgE reactivity to cod allergens observed in dogs was similar to that in humans, and this finding further supports the use of atopic dogs with fish allergy as a model for fish allergy in humans.
... Allergic diseases in canines include atopic dermatitis, gastroenteric inflammation, and anaphylaxis [15,16]. Owing to the numerous similarities between canine and human atopic dermatitis [17], atopic dogs have served as animal models for food allergies to cow's milk [11], corn [18], and nuts [12]. ...
Background:
IgE reactivity to fish allergens in atopic dogs, which are used as models for food allergy, has not been elucidated to date. We investigated IgE reactivity to crude extracts and purified allergens derived from the Pacific cod (Gadus macrocephalus) in atopic dogs to identify the allergenic proteins of cod.
Results:
The levels of specific IgE to crude cod extracts were measured in the sera of 179 atopic dogs, including 27 dogs with cod allergy, using enzyme-linked immunosorbent assay (ELISA). Specific IgE to crude cod extracts were present in 36 (20%) of the 179 atopic dogs and in 12 (44%) of the 27 dogs with cod allergy. The allergens in crude cod extracts were analyzed by ELISA, immunoblotting, and liquid chromatography-tandem mass spectrometry. In allergen component analysis, IgE reactivity to tropomyosin and enolase was observed in the sera of dogs with cod allergy. IgE reactivity to parvalbumin, collagen, and tropomyosin was evaluated using the sera of atopic dogs that tested positive for specific IgE to crude cod extracts. Among the 36 dogs with IgE reactivity to crude cod extracts, 9 (25%), 14 (39%), and 18 (50%) dogs tested positive for specific IgE to parvalbumin, collagen, and tropomyosin, respectively.
Conclusions:
The IgE reactivity to cod allergens observed in dogs was similar to that in humans, and this finding further supports the use of atopic dogs with fish allergy as a model for fish allergy in humans.
... Allergic diseases in canines include atopic dermatitis, gastroenteric in ammation, and anaphylaxis [15,16]. Owing to the numerous similarities between canine and human atopic dermatitis [17], atopic dogs have served as animal models for food allergies to cow's milk [11], corn [18], and nuts [12]. ...
Background: IgE reactivity to fish allergens in atopic dogs, which are used as models for food allergy, has not been elucidated to date. We investigated IgE reactivity to crude extracts and purified allergens derived from the Pacific cod (Gadus macrocephalus) in atopic dogs to identify the allergenic proteins of cod.
Results: The levels of specific IgE to crude cod extracts were measured in the sera of 179 atopic dogs, including 27 dogs with cod allergy, using enzyme-linked immunosorbent assay (ELISA). Specific IgE to crude cod extracts were present in 36 (20%) of the 179 atopic dogs and in 12 (44%) of the 27 dogs with cod allergy. The allergens in crude cod extracts were analyzed by ELISA, immunoblotting, and liquid chromatography-tandem mass spectrometry. In allergen component analysis, IgE reactivity to tropomyosin and enolase was observed in the sera of dogs with cod allergy. IgE reactivity to parvalbumin, collagen, and tropomyosin was evaluated using the sera of atopic dogs that tested positive for specific IgE to crude cod extracts. Among the 36 dogs with IgE reactivity to crude cod extracts, 9 (25%), 14 (39%), and 18 (50%) dogs tested positive for specific IgE to parvalbumin, collagen, and tropomyosin, respectively.
Conclusions: The IgE reactivity to cod allergens observed in dogs was similar to that in humans, and this finding further supports the use of atopic dogs with fish allergy as a model for fish allergy in humans.
... 6,7 An important limitation in this is that dog owners are responsible for observing and reporting the signs of a positive challenge. Although, in an experimental study involving research dogs with spontaneous food allergy, most dogs with IgEmediated food allergy exhibited a flare of signs within 48 h after provocation with individual food items, 8 the currently recommended length of food challenges, up to two weeks, originates from a study in which a single dog exhibited a relapse of signs two weeks after starting the provocation. 7 Of note is that such a duration before the recurrence of signs would be hardly reconcilable with either immunoglobulin E (IgE)-mediated or lymphocytemediated mechanisms. ...
... 6,7 An important limitation in this is that dog owners are responsible for observing and reporting the signs of a positive challenge. Although, in an experimental study involving research dogs with spontaneous food allergy, most dogs with IgEmediated food allergy exhibited a flare of signs within 48 h after provocation with individual food items, 8 the currently recommended length of food challenges, up to two weeks, originates from a study in which a single dog exhibited a relapse of signs two weeks after starting the provocation. 7 Of note is that such a duration before the recurrence of signs would be hardly reconcilable with either immunoglobulin E (IgE)-mediated or lymphocytemediated mechanisms. ...
Background
Food allergy is a possible cause of atopic dermatitis (AD) in dogs; it is typically diagnosed following an eight‐week elimination diet trial (EDT) and a provocation with the original diet. This lengthy procedure is difficult for owners and its interpretation may be unclear.
Hypothesis/Objectives
To test the effect of prednisolone used in the first weeks of an EDT in order to reduce the total time period for diagnosis. The goal was to perform food challenges earlier than after the traditionally recommended eight weeks.
Animals
Fifty‐three dogs with AD were included in the study.
Methods and materials
All dogs were fed a commercially available extensively hydrolyzed protein‐based commercial pet food and treated with prednisolone for at least two weeks to control pruritus and inflammation. Dogs were challenged two weeks after prednisolone finished, provided that no flare had occurred. Dogs with relapsing signs were fed the hydrolyzate for at least eight weeks with or without further prednisolone treatment.
Results
Ten of 53 dogs (19%) had no relapse after two weeks off prednisolone: they were subsequently challenged with their regular food, had a relapse of signs and were diagnosed with a food‐induced AD within four to six weeks of starting the EDT. In the other dogs, signs remained uncontrolled without prednisolone or relapsed rapidly after its discontinuation: they were considered nonfood‐allergic after an eight week EDT.
Conclusion and clinical importance
This study demonstrates that a shorter EDT is possible if the allergic pruritus and inflammation are initially controlled with a short course of glucocorticoids. This shortened trial is likely to improve owner adherence and facilitate the diagnosis of food allergy.
... In our earlier work, dark muscle tuna (Skipjack) hydrolysate has been shown to exhibit antioxidative properties with increasing degree of hydrolysis using Alcalase and Flavourzyme [11]. Hydrolyzed proteins have been suggested to be used to manage adverse food allergic reaction in human and in pets [12][13][14][15][16][17]. This relies on protein hydrolysis creating a wide range of peptides with a small size so that they are not recognized as antigen, therefore, rendering non-or hypoallergic properties. ...
Background: Oxidative stress and inflammation are inextricably linked and play major roles in the onset and development of Non-communicable diseases (NCD) which are the most common cause of death and disability in modern world. Hydrolyzed proteins have also been suggested to be used to manage adverse food allergic reaction. Therefore, this study aimed to investigate anti-inflammatory and anti-allergy activities of dark muscle tuna hydrolysates using biological cell line systems as a function of enzyme, the extent of hydrolysis and molecular weight range.
Methods: Dark muscle tuna hydrolysates were prepared with two different enzyme types; Alcalase and Flavourzyme. Anti-inflammation activity was measured by inhibitory effect of nitric oxide (NO) production on lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage cells. Anti-allergy was determined from ability of hydrolysates to inhibit b-hexsosaminidase (b-HEX) release from RBL-2H3 mast cells. Cytotoxicity was also investigated in both RAW 264.7 macrophage cells and RBL-2H3 mast cells.
Results: No cytotoxic effect on RAW 264.7 macrophage cells and RBL-2H3 mast cells was observed. The NO inhibition and b-HEX release were found significant in dose dependent manner (p<0.05). Alcalase hydrolysates demonstrated greater anti-inflammatory and anti-allergic activities than Flavourzyme hydrolysates (p<0.05). IC50 of both effects were lower than the unhydrolyzed control, > 45.44 mg/ml for NO inhibition and > 65.23 mg/ml for b-HEX release inhibition. These effects increased with the extent of hydrolysis and enzyme concentration. The peptide of lowest molecular weight range (< 3 KDa) was highest in anti-inflammatory and anti-allergic actions. Reducing secretion of TNF-a, IL-6 and IL-1b was found greater in Alcalase hydrolysate than Flavourzyme one.
Conclusions: Skipjack tuna dark muscle hydrolysates from Alcalase resulted in peptides with anti-inflammation activity, as determined by NO production in LPS-stimulated RAW 264.7 macrophage cells and anti-allergic properties as measured by a suppression of degranulation of sensitized RBL-2H3 cells. Anti-inflammatory effect may be due to their anti-oxidative capacity and relevant inflammatory factors attenuated with hydrolysate by reducing secretion of pro-inflammatory cytokine (TNF-a, IL-6 and IL-1b). Inhibition of b-HEX release by peptides may be due to membrane-stabilizing action or/and blockade of IgE antibody at fragment region.
Keywords: Skipjack tuna, anti-inflammation, enzymatic hydrolysate, dark muscle, anti-allergy
... Published studies failed to detect food-specific IgE in dogs with confirmed adverse reactions to those antigens (Mueller and Tsohalis, 1998) and serum IgE responses did not correlate with specific dietary exposures (Ricci et al., 2010). When clinical signs of AFR were stimulated in research dogs with AFR through an oral challenge, serum IgE changes did not predict the clinical outcome (Kennis et al., 2002;Jackson et al., 2003). In human medicine, antigen-specific IgE may persist in the absence of antigen exposure and clinical signs, or conversely, antigen-specific IgE may not necessarily reflect clinically relevant sensitisation against a particular allergen (Asero et al., 2007).The relatively high number of false negative and false positive reactions in our study concurs with these findings and provides further evidence that many clinically atopic dogs have negative test results and that healthy dogs can have increased concentrations of IgE antibodies. ...
... Published studies failed to detect food-specific IgE in dogs with confirmed adverse reactions to those antigens (Mueller and Tsohalis, 1998) and serum IgE responses did not correlate with specific dietary exposures (Ricci et al., 2010). When clinical signs of AFR were stimulated in research dogs with AFR through an oral challenge, serum IgE changes did not predict the clinical outcome (Kennis et al., 2002;Jackson et al., 2003). In human medicine, antigen-specific IgE may persist in the absence of antigen exposure and clinical signs, or conversely, antigen-specific IgE may not necessarily reflect clinically relevant sensitisation against a particular allergen (Asero et al., 2007).The relatively high number of false negative and false positive reactions in our study concurs with these findings and provides further evidence that many clinically atopic dogs have negative test results and that healthy dogs can have increased concentrations of IgE antibodies. ...
An elimination diet (ED) followed by re-challenge has been the reference standard to diagnose adverse food reactions (AFR) in dogs, but can be challenging to conduct. This study investigated the accuracy of a saliva-based test for food-specific IgA and IgM and an ELISA serum test for food-specific IgE. Three groups of dogs were tested. Group 1 (n = 11) included dogs with previously diagnosed and controlled AFR; group 2 (n = 15) comprised dogs with allergic dermatitis at the beginning of their ED; and group 3 (n = 16) was composed of clinically healthy research dogs. Saliva samples were collected from all groups and blood samples from group 1 and group 3. The results of clinical re-challenges with individual food components were compared with the test results. Specificity, sensitivity, positive and negative predictive values and likelihood ratios were determined.
Forty-one dogs completed the study; one dog was lost to follow up. There was a total of 163 re-challenges. Sensitivity, positive predictive value and likelihood ratio, specificity, negative predictive value and likelihood ratios were unsatisfactory for both tests in most instances, except for IgM testing in group 2, which had moderate specificity. There was no clear difference in the number of positive reactions between the allergic dogs and healthy dogs from a research population. Based on these results, the saliva test for food specific IgA and IgM and the ELISA serum test for food specific IgE were not reliable to diagnose adverse food reactions in dogs. Until more data are available, elimination diets remain the reference standard in the diagnosis of this disease.
... Multiple studies have shown that various commercial special diets with only one protein source on their label were contaminated and contained substances not listed on the label [57][58][59][60]. Highly hydrolysed food is an alternative, but some dogs allergic to chicken also react to diets containing hydrolysed chicken protein [61]. Therefore a home cooked diet by the owner is considered as diagnostic gold standard [52], where instead of commercial dry or canned food the owner purchases one type of meat and one carbohydrate source and prepares those him-/herself for the pet. ...
Abstract The purpose of this review article is to give an overview of atopic dermatitis in companion animals and of recent developments including knowledge on immunological background, novel treatment options and difficulties in disease management. The prevalence of hypersensitivities seems to be increasing. The pathogenetic mechanisms are not fully understood, yet multiple gene abnormalities and altered immunological processes are involved. In dogs and cats, the diagnosis of atopic dermatitis is based on history, clinical examination and exclusion of other differential diagnoses. Intradermal testing or testing for serum allergen-specific Immunoglobulin E is only used to identify allergens for inclusion in the extract for allergen immunotherapy. Symptomatic therapy includes glucocorticoids, ciclosporin, essential fatty acids and antihistamines. A selective janus kinase 1 inhibitor and a caninized monoclonal interleukin-31 antibody are the newest options for symptomatic treatment, although longterm effects still need to be assessed. The chronic and often severe nature of the disease, the costly diagnostic workup, frequent clinical flares and lifelong treatment are challenging for owners, pets and veterinarians. Patience and excellent communication skills are needed to achieve a good owner compliance and satisfactory clinical outcome for the animal.
... Both molecular diagnostic analysis and endoscopic allergy testing have been used to evaluate food allergies; however, the diagnostic performance has limited the use of either of these approaches. 55,66,67 Most studies regarding novel-ingredient or hydrolyzed diets for food allergies pertain to dogs with dermatologic signs with or without gastrointestinal signs. Hydrolyzed diets can be effective in up to 80% of dogs with experimentally induced or naturally occurring food allergies. ...
... Enzymatic hydrolysis of proteins into sufficiently tiny fragments eliminates immune recognition by allergic dogs (2,3). Such protein hydrolysates are expensive and principally used in veterinary, elimination and hypoallergenic diets. ...
Limited use of hydrolysed feather meal may be economically attractive
... Hydrolytic breakdown of proteins into sufficiently small fragments lowers the chance of immune recognition by patients that are allergic to the intact protein. Dogs with clinical sensitivity to soy were less severe responsive to the protein sources in hydrolysate form (5,6). Hydrolysed proteins are expensive and only used in veterinary products recommended as both elimination and hypoallergenic diets. These foods may have label descriptors such as low allergen, ultra allergen-free and anallergenic. ...
The term hypoallergenic in petfood labels relates to management of food allergy. True food allergy is uncommon in the general population of dogs and cats. In the marketplace, on the other hand, hypoallergenic foods are ubiquitous. This in itself is fine as well-formulated, complete and balanced hypoallergenic dog or cat foods provide good nutrition. Perceived rather than true food allergy is common. The abundance of hypoallergenic foods results from consumer demand and manufacturers going along. Food is often blamed for signs such as itching and diarrhea, leading to the self-diagnosis of food allergy. This conclusion may be reinforced by disappearing of signs after switching the animal to a hypoallergenic food. Understandably, the owner repurchases the brand. It is noteworthy that skin or gut problems may improve after diet change because of spontaneous recovery, shift in season or associated interventions. Hypoallergenic foods can be prescribed and sold by veterinarians. Food allergy can only be diagnosed by so-called elimination and provocation feeding tests. If the commercial, hypoallergenic, elimination food is associated with improvement, many owners choose to continue feeding the food without diagnosis. Blood testing for food allergy entails a high risk of a false-positive outcome. Prescribed hypoallergenic foods may be followed on by resembling products found in retail because of price and convenience. Thus, veterinary consultation tends to pave the way for hypoallergenic foods overall. The dictionary defines hypoallergenic as having little likelihood of causing an allergenic response. The term hypoallergenic is ambiguous as it has no legal definition and no defined measure for efficacy. EU legislation allows therapeutic petfoods with the purpose of reduction of certain ingredient and nutrient intolerances. These foods, which are often labeled hypoallergenic, must contain selected protein and/or carbohydrate source(s). Food allergy Food allergy is an individually-determined, immune-mediated reaction to a food component, which generally is a protein source. The major, non-specific clinical sign is itching (pruritus), which leads to scratching, licking and skin lesions. Diarrhea and vomiting occur less frequently. Dietary components can also elicit the symptoms by non-immune mechanisms; this is called food intolerance. In popular speech, it is joined under food allergy. Food allergy and intolerance are non-seasonal diseases commonly referred to as adverse reactions to food. Therapy consists of avoiding the offending food component(s). Published case studies in dogs indicate that about 65% of adverse reactions relate to beef, dairy products or wheat and 25% to lamb, soy, chicken or chicken egg (1). In cats, beef, dairy products and fish are associated with almost 90% of the cases (1). These figures are inflated by the common use of the incriminating protein sources as petfood ingredients. In dogs with non-seasonal pruritis entering
... Moreover, detection of the food allergen-specific IgE may fail because of several reasons: heterogeneity of IgE antibody (Peng et al., 1997), influence of specific IgG (Zimmermann et al., 1980) poor allergen preparation (Halliwell and DeBoer, 2001). However, allergen-specific IgE on mast cells in lesional skin induces degranulation by triggering food allergen (Olivry et al., 2001;Jackson et al., 2003) and certainly plays an important role in canine IgE-mediated food allergy. Therefore, the specific IgE test which is an examination of the alternative tests partially supports identification of offending foods. ...
Dogs with cutaneous adverse food reactions (CAFR) often have specific IgE to food allergens. Egg white, which is majorly composed of ovomucoid, ovalbumin, ovotransferrin, and lysozyme, is a food allergen in dogs. Information of the IgE reactivity to purified egg white allergens supports accurate diagnosis and efficiency treatment in humans. However, to the best of our knowledge, there have been no studies on the IgE reactivity to purified egg white allergens in dogs. Here, we investigated the IgE reactivity to crude and purified allergens of hen egg white in dogs with CAFR. First, when we examined serum samples from 82 dogs with CAFR for specific IgE to crude egg white by ELISA, 9.8% (8/82) of the dogs with CAFR showed the IgE reactivity to crude egg white. We then used sera from the eight dogs with positive IgE reactivity to crude egg white to examine the IgE reactivity to four purified allergens, ovomucoid, ovalbumin, ovotransferrin, and lysozyme, by ELISA. We found that 75% (6/8) of the dogs showed IgE reactivity to both ovomucoid and ovalbumin, and that 37.5% (3/8) of the dogs showed IgE reactivity to ovotransferrin. None (0/8) showed IgE reactivity to lysozyme. Moreover, validating these results, the immunoblot analyses were performed using the sera of the three dogs showing the highest IgE reactivity to crude egg white. Both anti-ovomucoid and anti-ovalbumin IgE were detected in the sera of these dogs, while anti-ovotransferrin IgE was not detected. Considering these, ovomucoid and ovalbumin appears to be the major egg white allergens in dogs with CAFR.
... Indeed, oral challenge with cornstarch resulted in an adverse reaction in 30% of dogs allergic to corn. 23 Further studies are needed to determine the allergenicity of these diets in corn allergic dogs. ...
Background:
Hydrolysed protein diets are used to diagnose and treat dogs with cutaneous adverse food reactions (CAFR). Little is known about what proportion of dogs hypersensitive to the native protein would react to its hydrolysed form.
Objectives:
To determine the clinical allergenicity of hydrolysed poultry feather (RCU) and chicken liver diets (HZD) in dogs with chicken induced CAFR.
Methods:
In this randomized, double-blinded, crossover trial, ten dogs with chicken induced CAFR were selected after a positive oral challenge to chicken meat and a negative one to corn. Test diets were fed for 14 days separated by a 14 day wash-out period. Owners rated pruritus daily with a Visual Analog Scale (PVAS). The challenge was ended if a flare in pruritus occurred (i.e. PVAS ≥5/10).
Results:
The median PVAS scores before feeding RCU and HZD were 0.9 and 1.7, respectively (Wilcoxon signed rank test, P = 0.46). Pruritus scores increased significantly after feeding HZD (Friedman's test, P < 0.001) but not after feeding RCU (P = 0.895). None of the dogs fed RCU, but four dogs fed HZD (40%), were withdrawn after a flare in pruritus developed (Fisher's test, P = 0.04). The maximal PVAS score was significantly higher after HZD (median: 4.7) compared to RCU (2.5) (Wilcoxon signed rank test, P = 0.01). One dog in each group was withdrawn due to diarrhoea.
Conclusions:
The hydrolysed poultry feather diet did not induce pruritus flares in dogs allergic to chicken in contrast to the hydrolysed chicken liver diet that led to pruritus flares in 40% of these dogs.
Canine atopic dermatitis (AD) is a common, genetically predisposed, inflammatory and pruritic skin disease. The variation in clinical presentations, due to genetic factors, extent of the lesions, stage of the disease, secondary infections, as well as resemblance to other non-atopic related skin diseases, can complicate a diagnosis of canine AD. A sub-group of the International Committee for Allergic Diseases in Animals (ICADA) was tasked with the development of a set of practical guidelines that can be used to assist practitioners and researchers in the diagnosis of canine AD. Online citation databases and abstracts from international meetings were searched for publications related to the topic, and combined with expert opinion where necessary. The final set of guidelines was approved by the entire committee.
The purpose of this article is to provide an overview of existing pharmacological models of canine dermatitis. Canine models of dermatitis have contributed significantly to our current understanding of the pathology of dermatitis and to the development of corresponding pharmacological interventions. Specifically, canine atopic dermatitis (AD) is reviewed here, as it is one of the most common inflammatory skin diseases in dogs. Canine AD also shares clinicopathological features with human AD, making the dog a natural and optimal model for human disease. Thus, pharmacological models of canine AD may be uniquely applicable to human pharmacological research. In this article, particular attention is dedicated to relevant in vivo, in vitro, and ex vivo models of canine AD, skin barrier defect models, pruritus models, and skin immunology models. Additionally, models of superficial pyoderma and food allergy are also discussed. With understanding of findings from canine models, researchers can select the most salient features for future pharmacological drug development. © 2023 Wiley Periodicals LLC.
This was a retrospective study of two groups of cases using commercial hydrolysate diet and homemade diet in the diagnosis of cutaneous adverse food reaction in 149 pruritic dogs by food restriction trial and food challenge. There was no statistically significant difference in frequencies of food-sensitized dogs, non-food-sensitized dogs, and dropped out cases between these two groups (p > 0.05). Seventy-one dogs (47.65%) completed the trial, 43 dogs had shown no reaction to any foods.
A 6-year-old, male, neutered, English Mastiff dog was presented for a second opinion due to chronic pruritus. The patient had been on methylprednisolone and chlorphenamine for four years. The diagnostic investigations included: swabs for bacterial and mycology culture, hair plugs for dermatophyte culture, acetate tape strips and deep skin scrapes, skin biopsies for dermatohistopathology, biochemistry, haematology, endocrinology, serology for canine scabies using enzyme-linked immunosorbent assay (ELISA) testing and serology for allergen specific IgE antibodies. The history and the diagnostics confirmed the diagnosis of canine atopic dermatitis. This case report details the treatment with lokivetmab, which is a caninised monoclonal antibody drug. At periods of flare ups, additional treatments were prescribed, such as systemic glucocorticoids and oclacitinib in order to manage the clinical signs. The treatment showed good response to the overall treatment management during the three year period of this atopic patient.
Background: IgE reactivity to fish allergens in atopic dogs, which are used as models for food allergy, has not been elucidated to date. We investigated IgE reactivity to crude extracts and purified Pacific cod (Gadus macrocephalus) allergens in atopic dogs to identify the allergenic proteins of cod.
Methods: Specific IgE to crude cod extracts in the sera of 179 atopic dogs, including 27 dogs with cod allergy, were measured using enzyme-linked immunosorbent assay (ELISA). The allergens of crude cod extracts were analyzed by ELISA, immunoblotting, and liquid chromatography-tandem mass spectrometry (LC-MS/MS). IgE reactivity to parvalbumin, collagen, and tropomyosin was evaluated using the sera of atopic dogs that were positive for specific IgE to crude cod extracts.
Results: Specific IgE to crude cod extracts were present in 36 (20%) of the 179 atopic dogs and 12 (44%) of the 27 dogs with cod allergy. In allergen component analysis, IgE reactivity to tropomyosin and enolase was observed in the sera of dogs with cod allergy. Among the 36 dogs with IgE reactivity to crude cod extracts, 9 (25%), 14 (39%), and 18 (50%) dogs had specific IgE to parvalbumin, collagen, and tropomyosin, respectively.
Conclusions: The dogs exhibited IgE reactivity to the cod allergens which observed in humans, providing support for the use of atopic dogs with fish allergy as a model for fish allergy in humans.
Background IgE reactivity to fish allergens in atopic dogs, which are used as models for food allergy, has not been elucidated to date. We investigated IgE reactivity to crude and purified Pacific cod (Gadus macrocephalus) allergens in atopic dogs to identify the allergenic components of cod.
Methods Specific IgE to crude cod allergens in the sera of 179 atopic dogs, including 27 dogs with cod allergy, were measured using enzyme-linked immunosorbent assay (ELISA). The allergenic components of crude cod antigen were analyzed by ELISA, immunoblotting, and liquid chromatography-tandem mass spectrometry (LC-MS/MS). IgE reactivity to parvalbumin, collagen, and tropomyosin was evaluated using the sera of atopic dogs that were positive for specific IgE to crude cod allergens.
Results Specific IgE to crude cod allergens were present in 36 (20%) of the 179 atopic dogs and 12 (44%) of the 27 dogs with cod allergy. In allergen component analysis, IgE reactivity to tropomyosin and enolase was observed in the sera of dogs with cod allergy. Among the 36 dogs with IgE reactivity to crude cod extracts, 9 (25%), 14 (39%), and 18 (50%) dogs had specific IgE to parvalbumin, collagen, and tropomyosin, respectively.
Conclusions The dogs exhibited IgE reactivity to the cod allergen components similar to that observed in humans, providing support for the use of atopic dogs with fish allergy as a model for fish allergy in humans.
Objective:
To assess the clinical accuracy of 2 serum-based assays and 1 saliva-based assay for detection of adverse food reaction (AFR) in dogs without clinical signs of disease.
Animals:
30 healthy client-owned dogs.
Procedures:
Dog owners completed an online survey to collect comprehensive information about their pets' diet history. From each dog, serum and saliva samples were obtained and submitted for AFR testing by means of 3 assays that assessed the immunoglobulin response to 24 foods. Assays A and B measured food allergen-specific IgE concentrations in serum, whereas assay C measured food allergen-specific IgA and IgM concentrations in saliva. Descriptive data were generated, and Fisher exact tests were used to assess the respective associations between positive test results and specific food ingredients to which dogs were exposed.
Results:
Assays A, B, and C yielded positive results for 26, 18, and 30 dogs, respectively. All dogs had positive results for at least 1 assay. The median (range) number of foods or ingredients to which dogs tested positive was 10.5 (0 to 24) for assay A, 1 (0 to 13) for assay B, and 12.5 (4 to 22; IgM) and 3 (0 to 24; IgA) for assay C. Positive test results were not significantly associated with prior food exposure.
Conclusions and clinical relevance:
Saliva and serum assays for AFR often yielded positive results for apparently healthy dogs and are not recommended for clinical use. Elimination diet trials remain the gold standard for diagnosis of AFR in dogs.
Background
In humans, a cross‐reactive clinical allergy has been reported between three chicken and fish meat proteins: beta‐enolase, aldolase A and parvalbumin.
Objective
To evaluate if IgE cross‐reactivity between chicken and fish also existed in the dog.
Animals
Sera from dogs with suspected allergic skin disease and with IgE against chicken and fish.
Methods and materials
Sera were analysed by ELISA and immunoblotting with chicken, white fish (haddock and cod) and salmon extracts. Reciprocal inhibition ELISAs and inhibition immunoblots were then performed. Protein sequencing of bands identified on multiple extracts was determined by mass spectrometry.
Results
Out of 53 archived canine sera tested by ELISA against chicken, white fish or salmon, 15 (28%), 12 (23%) and 26 (49%), respectively, had elevated IgE against one, two or all three of these extracts. Seven of the triple‐reactive sera were subjected to reciprocal inhibition ELISAs. A >50% inhibition was found between chicken–fish, chicken–salmon and fish–salmon in seven, four and five of seven dogs, respectively. Immunoblotting identified multiple IgE‐binding proteins of identical molecular weights in the three extracts; these were partially to fully cross‐reactive by inhibition immunoblotting. Mass spectrometry identified nine cross‐reactive proteins as: pyruvate kinase, creatine kinase, alpha‐actin, glyceraldehyde‐3‐phosphate dehydrogenase, beta‐enolase, aldolase, malate dehydrogenase, lactate dehydrogenase and triose‐phosphate isomerase 1. All of these have been reported previously as fish, shellfish and/or chicken allergens for humans.
Conclusions and clinical importance
Whether any of these newly identified IgE cross‐reactive chicken–fish allergens is the cause of clinical allergy needs to be determined in dogs reacting to at least two of these common food sources.
Objectives
Several companies offer saliva and/or hair tests for food and environmental allergies in companion animals, but provide no validation of test accuracy. We examined one such hair and saliva allergy test to determine whether it could reliably differentiate between a normal dog and an allergic dog, and to examine test repeatability.
Materials and Methods
Ten fur and saliva samples were submitted from a known allergic dog and a normal, non‐allergic dog. Five fake fur samples and water were also submitted to determine whether the test could differentiate between a real dog and toy animal. The company performed testing for 128 food and environmental allergens. Statistical analyses were performed to determine whether the response distribution differed significantly between dogs, using the Pearson chi‐square coefficient, as well as to determine test–retest reliability by calculating Cohen's kappa for each allergen.
Results
The distribution of test results from samples obtained from allergic, non‐allergic or fake dogs was not different from that expected due to random chance. Test–retest reproducibility was poor to slight.
Clinical Significance
Hair and saliva testing should not be used to diagnose allergies and is not a substitute for veterinary‐directed allergy evaluation and diagnostics.
Background:
The diagnosis of adverse food reaction (AFR) is based on an eight week elimination diet (ED) and is confirmed by relapse upon re-challenge with the previously fed diet. Hydrolysed EDs are commonly used for this purpose.
Objective:
To evaluate a commercially available hydrolysed fish protein and rice starch ED for the diagnosis of AFR.
Animals:
Fifty nonseasonally pruritic dogs.
Methods and materials:
Pruritus was assessed with a Visual Analog Scale, lesions with the Canine Atopic Dermatitis Lesions Index and quality of life with a validated questionnaire on days 0 and 56. Antimicrobial treatments were permitted during the first four weeks, and corticosteroids and oclacitinib during the first six weeks. Dogs showing at least 50% pruritus improvement were separately challenged with their prior diet, fish and rice.
Results:
Thirty eight dogs completed the ED, four were dropped out due to worsening clinical signs, three to low palatability and five were lost to follow-up. In 24 dogs, pruritus improved by >50% and 22 underwent dietary challenges. Of these, 15 reacted to their prior diets and were diagnosed with AFR, whereas seven did not relapse (and a diagnosis of AFR was considered to be doubtful). Five dogs reacted to fish and four to rice. Of the 14 dogs in which pruritus did not improve, some underwent a second ED and others were successfully treated for atopic dermatitis.
Conclusion and clinical importance:
The hydrolysed fish and rice diet seemed to be a useful ED for the diagnosis of AFR, even in dogs allergic to fish or rice.
Background:
Adverse food reaction (AFR) is diagnosed with a two month elimination diet (ED), followed by challenge with the original food.
Hypothesis/objectives:
To evaluate reactivity of selected EDs and performance of a Western blot serological test for the diagnosis of AFR.
Animals:
Twenty five food reactive (FR) and 13 non food reactive (NFR) privately owned dogs.
Methods:
Sera were tested for antibodies against hydrolyzed poultry feather (RCA), hydrolyzed soy (PHA), hydrolyzed fish (FUH), limited antigen horse and potato (THP), fresh horse meat and the offending food for each FR dog as documented by provocative challenge.
Results:
Fourteen sera were negative and two positive to all foods. Sera from five of 13 NFR and three of 25 FR dogs were reactive to hydrolyzed foods. The RCA diet was recognized by four of 38, FUH by six of 38 and PHA by one of 28 samples. THP was recognized by 14 of 33 and fresh horse by one of ten dogs that had never eaten horse meat. The test correctly identified one of 15 dogs allergic to FUH. Twenty of 25 FR sera were negative for the dogs' respective offending foods (20% sensitivity), whereas four of 13 NFR sera were positive to the dogs' usual diets (69% specificity).
Conclusion and clinical importance:
Western blot analysis cannot be considered as a valid tool for the diagnosis of AFR; it may serve as an aid in selecting an ED.
Canine enteropathy is often a difficult condition to treat. The cause is usually idiopathic and the treatment process can be stressful for both patients and their owners. Procedures such as endoscopy are unable to assist in diagnosing the root of the problem, but merely confirm inflammation and damage to the digestive tract is present. The condition can be confused with adverse food reactions due to similar clinical signs, however when challenged with their original diets, patients with canine enteropathy do not relapse. Studies have shown that hydrolysed diets are successful in treating the gastrointestinal signs associated with adverse food reactions. These diets prevent immune recognition of an intact protein by removing the allergenic epitopes in a chemical reaction called enzymatic hydrolysis. There are minimal studies available proving the efficacy of hydrolysed protein diets in treating enteropathy when an adverse food reaction is not the cause, however they all concur that patients remain in remission post treatment. This review aims to explore the studies available which test the efficacy of hydrolysed diets in treating enteropathies and discuss their use in the veterinary practice.
An 11-month-old ASA 1 male miniature dachshund was anaesthetised for neutering. Butorphanol and midazolam were administered as preanaesthetic medication along with cefazolin. Anaesthesia was induced with propofol and maintained with isoflurane. Latex products (surgical gloves and a breathing bag) were used intraoperatively. Intraoperative vital signs were within normal ranges. Approximately 5 min after extubation, the dog developed intense urticarial erythema, hypotension and pulmonary oedema. First-line treatment with repeated intramuscular epinephrine, oxygenation, fluid loading, corticosteroids and antihistamines to address severe hypotension was unsuccessful. Additional vasopressin, continuous epinephrine infusion, mechanical ventilation and cardiopulmonary resuscitation proved unsuccessful and the owners opted for euthanasia. The causative agent remains unclear; serological or skin tests were not performed. This is the first report of severe perioperative anaphylactic shock in a dog unresponsive to current therapeutic recommendations based on epinephrine administration. Further research is warranted to advance clinical guidelines for managing anaphylaxis in dogs.
How well can you answer pet owners' questions about proper diet and feeding? Canine and Feline Nutrition, 3rd Edition describes the role of nutrition and its effects upon health and wellness and the dietary management of various disorders of dogs and cats. By using the book's cutting-edge research and clinical nutrition information, you'll be able to make recommendations of appropriate pet food and proper feeding guidelines. Pet nutrition experts Linda P. Case, MS, Leighann Daristotle, DVM, PhD, Michael G. Hayek, PhD, and Melody Foess Raasch, DVM, provide complete, head-to-tail coverage and a broad scope of knowledge, so you can help dog and cat owners make sound nutrition and feeding choices to promote their pets' health to prolong their lives. Tables and boxes provide quick reference to the most important clinical information. Key points summarize essential information at a glance. A useful Nutritional Myths and Feeding Practices chapter dispels and corrects common food myths.New clinical information covers a wide range of emerging nutrition topics including the role of the omega-3 and omega-6 fatty acid families in pet health and disease management. Coverage of pet food safety and pet food ingredients includes both commercially and home-prepared foods and provides answers to pet owners' questions on these topics. Completely updated content reflects the latest findings in clinical nutrition research. Information regarding functional ingredients and dietary supplementation provides a scientifically based rationale for recommending or advising against dietary supplements. Guidelines for understanding pet food formulations and health claims differentiate between "market-speak" and actual clinical benefits for patients, with practice advice for evaluating and selecting appropriate foods.
Adverse food reactions occur in human as well as veterinary patients and systematic comparison may lead to improved recommendations for prevention and treatment in both. In this position paper, we summarize the current knowledge on immediate type food allergy versus other food-adverse reactions in companion animals, and compare this to the human situation. While the prevalence of food allergy in humans has been well studied for some allergens, this remains to be investigated for animal patients, where owner-reported as well as veterinarian-diagnosed food adverse reactions are on the increase. The characteristics of the disease in humans versus dogs, cats, and horses are most often caused by similar, but sometimes species-dependent different, pathophysiological mechanisms, prompting the specific clinical symptoms, diagnoses and treatments. Furthermore, little is known about the allergen molecules causative for type I food allergy in animals which, like in human patients, could represent predictive biomarkers for risk evaluation. The definite diagnosis of food allergy relies -as in humans- on elimination diet and provocation tests. Besides allergen avoidance in daily practice, novel treatment options and tolerization strategies are underway. Taken together, numerous knowledge gaps were identified in veterinary food allergy, which need to be filled by systematic comparative studies. This article is protected by copyright. All rights reserved.
To establish an ELISA for detection of serum total IgE concentration in dogs and to analyze IgE values in a dog colony.
147 healthy Beagles (31 males and 116 females).
2 canine IgE-specific polyclonal antibodies elicited by 2 recombinant fragments of the epsilon chain in hens were used to develop a capture ELISA specific for serum total IgE concentration. The IgE values were calculated by comparing serum dose-response curves (1:50 to 1:6,400) with a reference serum pool assigned 100 relative ELISA units (REU). Results-Mean IgE concentration in female Beagles was 51.2 REU (range, 0 to 337.8 REU; median, 31.4 REU), whereas mean IgE concentration in male dogs was only 7.5 REU (range, 0 to 32.6 REU; mean, 3.6 REU). Distribution of IgE values was skewed; approximately 80% of dogs had IgE values < 50 REU. Analysis of natural logarithmically transformed IgE values indicated that sex and age significantly (P < 0.05) influenced IgE values; mean serum IgE values increased until the age of 4 years. Heritability estimates of IgE concentration indicated a trend toward a genetic influence.
A reliable capture ELISA specific for canine IgE was developed. Serum total IgE values vary with age and sex in the sample population.
Serum total IgE concentration can now be evaluated in various dog breeds and, subsequently, in dogs with IgE-mediated diseases provided that these significant influences are accounted for. Serum total IgE values may then prove to be of diagnostic value, similar to their use in human beings.
Thirteen food-allergic dogs were studied to evaluate the efficacy of feeding a commercially available egg and rice diet, intradermal skin testing, and serologic testing by elisa for diagnosing and/or characterizing food hypersensitivity. Feeding of a home-cooked whole lamb meat and rice diet for 3 weeks, followed by challenge with each dog's regular diet, served as the standard for diagnosing food hypersensitivity. Each dog underwent provocative testing with 6 individual ingredients to determine as many of its dietary allergens as possible. Prior to skin testing and serologic testing by elisa , most dogs had been recently exposed to the offending diet and subsequently manifested clinical signs of allergy. All dogs that tolerated the aforementioned commercial diet were exposed to it for at least 7 weeks; 84.6% of food-hypersensitive dogs ate the commercial diet with impunity. Of the 2 reactors to the commercial diet, only 1 became pruritic in response to provocation testing with chicken eggs. Low sensitivity and high specificity were found for skin testing and the elisa , indicating a lack of true- and false-positive reactions. Neither the positive nor negative predictive values adequately predicted positive and negative reactions, respectively, for either test. On the basis of these results, the commercial diet, skin testing, and anti-IgE elisa cannot replace an owner-prepared food elimination diet for food hypersensitivity testing in dogs.
Atopic dermatitis is a common allergic disease manifestation in dogs; however, there is no correlation between clinical disease and detectable total serum IgE. Auto antibodies of the IgG subclass against IgE may affect the detection of serum IgE by immunoassay and may be important in the regulation of IgE production by B cells. ELISA were developed to detect serum antibodies specific for IgE using a newly available canine monoclonal IgE of known antigen specificity, generated from a canine × murine heterohybridoma. To test for correlation of auto IgG anti-IgE levels with manifestation of atopic dermatitis, the sera from 101 atopic dogs were compared with sera from non-atopic dogs of various breeds, foxhounds manifesting clinical signs of demodectic acariasis and helminth parasitized random bred dogs for quantities of IgG anti-IgE measured in units/ml compared to a high titer standard serum. To test for serum effects on quantitation of IgE, known amounts of canine monoclonal IgE were added to various sera and measured by capture ELISA with detecting monoclonal antibodies specific for heat labile or heat stabile epitopes. Unheated sera from dogs manifesting clinical atopic dermatitis and helminth parasitized dogs had levels of IgG anti-IgE that were significantly lower than various breeds of dogs not manifesting dermatologic lesions and foxhounds manifesting demodectic acariasis. Heating sera at 56°C for 3 h to denature the high affinity binding site on the IgE heavy chain caused a marked increase over non-heated sera in detectable IgG angi-IgE in almost all dogs. This increase was most profound in helminth-infected dogs and foxhounds manifesting demodectic mange with 7 fold increases each, respectively, and in atopic dogs with a 5 fold increase compared to 3 fold increases for clinically-normal springer spaniels and all soft coated wheaten terriers. The terriers demonstrated an association of lower heated serum values of IgG anti-IgE with manifestation of a familial syndrome of protein-losing enteropathy and protein-losing nephropathy. The ability of mouse anti-canine IgE monoclonal antibodies specific for either heat labile or heat stabile epitopes to detect canine monoclonal IgE added to sera in known amounts varied from serum to serum and at different concentrations of the same serum, but did not correlate with IgG anti-IgE values for these sera. The range of absolute levels of serum IgE in dogs showing little or no inhibition of detection of added IgE was
Specific immunotherapy (SIT) using a standardized mite extract is effective and safe when administered under optimal conditions. However, the duration of its effectiveness after cessation of treatment remains unknown. Forty asthmatic subjects who had received SIT with a standardized Dermatophagoides pteronyssinus (Der p) extract under the same protocol were studied. All had received SIT for a period of 12–96 months and were not receiving pharmacologic treatment. The FEV1 was within normal range in all patients. After cessation of treatment, patients were followed for up to 3 years at 6-month intervals. The patient was considered to have relapsed when symptoms of asthma and/or rhinitis occurred and/or when pulmonary function tests were impaired. Skin tests with increasing concentrations of Der p were carried out before and at the end of SIT. Forty-five percent of the patients did not relapse. The duration of efficacy of SIT was related to the duration of SIT itself (P < 0.04). Most patients who did not relapse had a decrease in skin test reactivity at the end of SIT, whereas most patients who relapsed did not show any change (P < 0.003). The duration of efficacy of SIT after its cessation depends upon the duration of SIT and may be predicted by the effect of SIT on skin tests.
One hundred suspected allergic dogs were skin-tested with 9 food extracts, in addition to other inhalant and insect allergens. Forty-eight of the dogs had +2 or greater intradermal reactions to 1 or more food extracts at concentration of 1,000 protein nitrogen units/ml. Thirty of the food extract-positive dogs were fed a restrictive hypoallergenic diet. Of these 30 dogs, 3 improved, then allergy signs worsened when they were challenge-exposed with the original diet. Fifty-two dogs did not have skin test reactivity to any of the 9 food extracts. Of these 52 dogs, 35 were fed a restrictive diet. Six improved, then allergy signs worsened when dogs were challenge-exposed with the original diet. Skin-testing with selected allergenic food extracts was not useful in identifying food-sensitive dogs.
Thirteen food-allergic dogs were studied to evaluate the efficacy of feeding a commercially available egg and rice diet, intradermal skin testing, and serologic testing by ELISA for diagnosing and/or characterizing food hypersensitivity. Feeding of a home-cooked whole lamb meat and rice diet for 3 weeks, followed by challenge with each dog's regular diet, served as the standard for diagnosing food hypersensitivity. Each dog underwent provocative testing with 6 individual ingredients to determine as many of its dietary allergens as possible. Prior to skin testing and serologic testing by ELISA, most dogs had been recently exposed to the offending diet and subsequently manifested clinical signs of allergy. All dogs that tolerated the aforementioned commercial diet were exposed to it for at least 7 weeks; 84.6% of food-hypersensitive dogs ate the commercial diet with impunity. Of the 2 reactors to the commercial diet, only 1 became pruritic in response to provocation testing with chicken eggs. Low sensitivity and high specificity were found for skin testing and the ELISA, indicating a lack of true- and false-positive reactions. Neither the positive nor negative predictive values adequately predicted positive and negative reactions, respectively, for either test. On the basis of these results, the commercial diet, skin testing, and anti-IgE ELISA cannot replace an owner-prepared food elimination diet for food hypersensitivity testing in dogs.
Canine popliteal lymph node cells taken at the onset of clinical disease from a rear limb infected with the filarial nematode Brugia pahangi were fused with mouse myeloma cell line P3X63.Ag8.653 cells. Of the several canine immunoglobulin-producing clones from this fusion, one was found to produce canine IgE specific for a filarial nematode antigen. The cell line has undergone limiting dilution cloning six times over the past 3 years and continues to produce monoclonal antibody of the IgE subclass at a rate of greater than 3 mg/l. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) of the cell culture supernatant protein that bound to protein A beads, showed bands at molecular weights (MW) of approximately 75,000 and 25,000 that were characteristic of epsilon and kappa or lambda chains, respectively. A mouse monoclonal antibody specific for canine IgE bound the 75,000 MW band, as demonstrated by Western blot. Western blots of aqueous extracts of adult filarial nematodes demonstrated binding of the canine IgE monoclonal antibody to a single 35,000 MW peptide from B. pahangi but not Dirofilaria immitis; immunochemistry using frozen sections of adult worms, microfilariae and fourth stage larvae revealed focal binding of the monoclonal IgE to worm tissue adjacent to dorsal and ventral cords of only Brugia adults.
Concentrations of total serum IgE, IgA, and IgG were measured in 36 atopic and 16 parasitized dogs, and compared them with 30 healthy control dogs. IgE was measured using enzyme-linked immunosorbent assay. IgA and IgG were measured using radial immunodiffusion assays. Mean total serum immunoglobulin (Ig) E concentrations in healthy, atopic and parasitized dogs were 7.1 units (U) ml-1, 5.8 U ml-1 and 14.3 U ml-1, respectively. Mean total serum IgA concentrations in the same groups were 103.3 mg dl-1, 63.2 mg dl-1 and 67.3 mg dl-1, respectively. Mean total serum IgG concentrations were 1066 mg dl-1, 1621 mg dl-1 and 1480 mg dl-1 in the three groups. There was no significant difference in IgE concentrations between these groups of dogs. IgA levels were significantly lower in atopic and parasitized dogs compared with healthy dogs (P < or = 0.05), whereas IgG levels were significantly higher in the atopic and parasitized dogs (P < or = 0.005). These results suggest that measurement of total serum IgE would be of no benefit in the preliminary clinical investigation of a suspected atopic dog. The lower IgA and higher IgG concentrations in both atopic and parasitized dogs suggest that similar regulatory mechanisms governing immunoglobulin synthesis occur in canine allergic and parasitic disease, promoting IgG synthesis but down-regulating IgA production.
Peripheral blood mononuclear cells (PBMCs) from patients with atopic dermatitis (AD) selected as being sensitive to hen's egg or cow's milk responded to food antigens, ovalbumin, or bovine serum albumin, with significantly enhanced DNA synthesis compared with the DNA synthesis in PBMCs from nonatopic control subjects and food-sensitive patients with immediate symptoms. Patients were treated with elimination diets. Symptoms of AD had been in remission during elimination diets. The levels of specific IgE antibodies to hen's egg or cow's milk decreased during elimination diets in patients with positive radioallergosorbent test (RAST). In patients with negative RAST, specific IgE antibodies remained negative during elimination diets. The proliferative responses of PBMCs to food antigens also decreased during elimination diets in patients with proliferative responses before elimination diets. Taken together, specific IgE antibodies to food antigens are useful indexes of the effect of elimination diets in food-sensitive patients with AD and positive RAST, and proliferative responses of PBMCs to food antigens are useful indexes of the effect of elimination diets in food-sensitive patients with AD and proliferative responses of PBMCs.
Specific immunotherapy (SIT) using a standardized mite extract is effective and safe when administered under optimal conditions. However, the duration of its effectiveness after cessation of treatment remains unknown. Forty asthmatic subjects who had received SIT with a standardized Dermatophagoides pteronyssinus (Der p) extract under the same protocol were studied. All had received SIT for a period of 12-96 months and were not receiving pharmacologic treatment. The FEV1 was within normal range in all patients. After cessation of treatment, patients were followed for up to 3 years at 6-month intervals. The patient was considered to have relapsed when symptoms of asthma and/or rhinitis occurred and/or when pulmonary function tests were impaired. Skin tests with increasing concentrations of Der p were carried out before and at the end of SIT. Forty-five percent of the patients did not relapse. The duration of efficacy of SIT was related to the duration of SIT itself (P < 0.04). Most patients who did not relapse had a decrease in skin test reactivity at the end of SIT, whereas most patients who relapsed did not show any change (P < 0.003). The duration of efficacy of SIT after its cessation depends upon the duration of SIT and may be predicted by the effect of SIT on skin tests.
Histamine release from canine leucocyte-enriched peripheral blood preparations was measured in atopic, non-atopic and artificially sensitised dogs after immunological challenge with D. farinae antigen and anti-IgE. Total cell histamine and spontaneous histamine release was also measured. The total cell histamine content of equal leucocyte preparations was not statistically significant between the atopic and non-atopic groups. At all dilutions of antigen a higher amount of histamine was released from the leucocytes of atopic dogs than was seen in the non-atopic group. No histamine release in response to D. farinae was seen in the sensitised dogs although a statistically significant increase in serum D. farinae-specific IgE could be demonstrated after sensitisation (P < 0.03). Histamine release in response to anti-IgE was significantly greater in the atopic dogs than the non-atopic dogs (P < 0.004) and the sensitised dogs (P < 0.003). There was no statistically significant difference in total serum IgE between the groups. The authors conclude that the leucocytes of atopic dogs have a greater tendency to release histamine than those of normal and artificially sensitised dogs and that this is independent of the concentration of total serum IgE or antigen-specific IgE. They suggest that there may be immunoregulatory abnormalities in atopic dogs intrinsic to the atopic state as is described in man.
The renewed interest in food allergy and its investigation has been hampered by the lack of an appropriate animal model with similar comparative aspects of form and function relative to humans. Therefore we have been characterizing an inbred colony of high immunoglobulin E-producing dogs that were immunized subcutaneously with food antigen extracts in alum and that developed clinical manifestations of food allergy after oral challenges with food antigen. These dogs had appreciably high IgE antibody titer to specific food antigens, as measured by an enzyme-labeled immunodot assay. Skin test results for the food antigens were consistently positive, as evidenced by a wheal-and-flare reaction. Gastroscopic food sensitivity was tested through an endoscope by injecting allergenic food extracts into the gastric mucosa after intravenous injection of Evans blue dye. Mucosal changes included swelling and erythema, some petechiae and blue patching, and in some instances generalized gastric erythema and hyperperistalsis. Examination of immediate-reaction biopsy specimens revealed edema and few inflammatory cells. Examination of late-reaction biopsy specimens revealed increased eosinophil and mononuclear cell infiltrations typical of late-phase allergic inflammatory responses. Direct mucosal challenge with food extracts confirmed the clinical and immunologic evidence of food allergy in these immunized dogs and suggests the usefulness of the atopic dog as a model for food allergy. This model might also be useful in detecting hidden food allergies in unexplained inflammatory gastrointestinal tract diseases.
Experimental sensitization in dogs has revealed that the capacity to produce high levels of IgE against a variety of allergens (high IgE responders), an essential characteristic of the atopic state, is a genetic trait inherited in a dominant manner. In high IgE responder dogs spontaneous development of IgE to inhaled allergens, such as house dust mites, on the other hand, represents an apparent phenotype very similar to that observed in human atopic families. The full potential of the high IgE response gene appears to be fulfilled only under some conditions such as early and repeated exposition to allergens. It is therefore quite possible that the true phenotype of human atopy would also be inherited in a dominant fashion but not constantly expressed. This would explain why the increase in the prevalence of allergic diseases started long before the environmental factors currently accused could have been at play. This hypothesis, which can be verified experimentally, has important implications for the future of allergy.
Total serum immunoglobulin (Ig) E and A levels were analysed in 233 healthy dogs as basis for comparison with atopic dogs in future studies. They were measured by ELISA in a group of non- colonised dogs of various breeds (group A) and three groups of colonised dogs including one German Shepherd and two Beagle kennels (groups B-D). IgE levels from non-colonised dogs were significantly higher than the ones of German Shepherds and Beagles C (P<0.05). IgA levels were alike in all groups except for the German Shepherds which displayed the lowest levels. Age and sex were not identified as common significant cofactors for IgE and IgA levels in all groups and IgE levels correlated negatively with IgA only in non-colonised dogs. In conclusion, IgE and IgA levels seem to be mainly influenced by genetic background. Thus use of total serum IgE as a diagnostic tool in the atopic dogs required extensive family data and therefore appears most suitable for research purposes within specific, well defined dog populations.
As a consequence of the general increase in allergic sensitization, the prevalence of hypersensitivity reactions to multiple foods that share homologous proteins has become a significant clinical problem. A variety of these allergens conserved among plants (eg, profilin and lipid transfer proteins) and animals (eg, tropomyosin and caseins) have been characterized. Although studies with molecular biologic techniques have elucidated the nature of these ubiquitous allergens, clinical studies have lagged behind. The physician is called on to determine the risk of reaction to related foods among legumes, tree nuts, fish, shellfish, cereal grains, mammalian and avian food products, and a variety of other plant-derived foods that may share proteins with pollens, latex, and each other. Clinical evaluations require a careful history, laboratory evaluation, and in some cases oral food challenges. The pitfalls in the evaluation of food allergy-unreliable histories and limitations in laboratory assessment primarily caused by false-positive skin prick test responses/RAST results are magnified when dealing with cross-reactive proteins. This review focuses on the clinical data regarding cross-reacting food allergens with the goal of providing a background for improved risk assessment and a framework on which to approach these difficult clinical questions.
Three dogs were examined because of episodes of recurrent pruritic dermatitis in the spring, the season of Japanese cedar (Cryptomeria japonica, CJ) pollination in Japan. The dogs were shown to be sensitive to CJ pollen allergen using intradermal testing and antigen-specific IgE measurement. Fluorometric enzyme-linked immunosorbant assay (ELISA) showed increased concentrations of IgE specific to Cry j 1 and a negative result for Cry j 2 in the three dogs. The concentrations of IgE specific to Cry j 1 during the season of CJ pollination were higher than the concentrations found during the off-season in all the dogs, and the variation in the concentrations correlated with the variation in clinical signs. Peripheral blood mononuclear cells showed apparent proliferative responses to crude CJ pollen antigen and Cry j 1 during CJ pollination season. These findings indicated that Cry j 1 was the major allergen recognized by IgE and lymphocytes and resulted in the development of type I hypersensitivity to CJ pollen allergen in these atopic dogs.
Over a period of one year, 251 dogs were presented to a UK-based dermatology referral clinic. Eighty-five of these were either diagnosed as having symptoms compatible with atopy (58 dogs), or suffered from chronic otitis or recurrent pyoderma. All 85 were placed on a carefully restricted diet for eight to nine weeks in an attempt to establish whether the symptoms were due to food sensitivity. In total, 19 were shown to have food sensitivity, representing 7.6 per cent of all dogs presented to the clinic, and one-third (32.7 per cent) of those dogs with signs compatible with a diagnosis of atopy. In five dogs with proven food sensitivity, otitis was the principal clinical sign and, in two others, recurrent pyoderma. In the population studied, labradors appeared to be predisposed to the condition. Improvement was monitored by asking owners to assess their dog's symptoms on an ordinal scale of pruritus. In those cases in which food sensitivity was confirmed, significant reduction in pruritus occurred. Most of these could be maintained long term on a commercial restricted-component diet. Particular effort was made to ensure owner compliance with the diet trials, using an explanation and model based upon a Venn diagram showing assumed links between atopy and several 'flare factors'. It was found that this approach significantly enhanced client understanding and cooperation. It is concluded that a careful approach, monitored by active clinical audit, will help to establish the true incidence of food sensitivity.
The purpose of the pilot study reported here was to evaluate serum and fecal total and allergen-specific immunoglobulin E (IgE) responses to dietary change in five Maltese x beagle dogs with suspected food hypersensitivity, compared with those of five clinically normal dogs. Clinical parameters (pruritus, otitis, and diarrhea) improved in the Maltese x beagle dogs during feeding of a novel diet, and signs were exacerbated by oral allergen provocation. Relative concentrations of serum and fecal wheat-, corn-, and milk-specific IgE were determined by use of an ELISA. The onset of clinical signs of disease was accompanied by an increase in serum allergen-specific IgE concentrations. In contrast, changes in clinical signs of disease or allergen-specific IgE values were not seen in the control group undergoing the same regimen. Total serum IgE concentration was measured by use of the ELISA, and comparison with known quantities of a monoclonal IgE allowed absolute values to be reported. Values were high in the Maltese x beagle colony (7 to 34 microg/ml), compared with those in the control dogs (0.7 to 6 microg/ml). Total serum and total fecal IgE concentrations did not change in either group during the study. Although allergen-specific IgE was detected in the feces of both groups, significant interassay variability made interpretation of the results difficult. The authors concluded that these Maltese x beagle dogs satisfied the currently recognized clinical criteria for the diagnosis of canine food hypersensitivity. Furthermore, the clinical and serologic responses seen in these dogs in response to oral allergen provocation suggest that this may be a useful model for the study of spontaneous food hypersensitivity.
Comparison of a hydrolysed soy protein diet containing cornstarch with a positive and negative control diet on corn or soy sensitive dogs
- K M Beale
- D P Laflamme