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... Examples of APCs covered dendritic cells, Langerhans' cells, and macrophages. Recently, there was giant interest to determine position of APCs in regulating inflammation, however classically their position has been taken into consideration to switch the allergen to a regulating T-helper lymphocyte (additionally called a Th lymphocyte or CD4 lymphocyte) [15][16] . ...
... Th2 lymphocytes realise mediators that facilitate defeat parasites. Interestingly, the Th2 lymphocytes regulate the sort of inflammation seen in allergic conditions [15][16] . ...
... IL-4, IL-5 (eosinophil activation), associate degree IL-13 are particularly important Th2 cytokines. T-cell receptors are thought to play a very important role in controlling the inflammation [15][16] . ...
Allergic rhinitis addresses a hyperactivity of the resistant framework in any case harmless particles making a fiery reaction where none is required. Allergic Rhinitis is clinically represented by a mixture of two or additional nasal symptoms: running, blocking, itching and sneezing. Allergic rhinitis is regularly partitioned by age, seriousness, and duration of symptoms. Investigation represents how epidemiologic evaluations on the commonness of hypersensitive or allergic rhinitis shift considerably with whether both clinical appraisal and testing were utilized to make the determination. The treatment of allergic rhinitis should combine allergen avoidance, pharmacotherapy and allergen immunotherapy. Treatments of allergic rhinitis include intranasal corticosteroids, oral and topical antihistamines, decongestants, intranasal cromolyn, intranasal anticholinergics. First-generation and Second-generation oral antihistamines and intranasal corticosteroids are the most effective modality for treating allergic rhinitis. Immunotherapy is an efficient immune-modulating treatment that ought to be counseled if pharmacologic medical care for allergic rhinitis isn't effective or not tolerated. This article provides an overview of the prevalence, pathophysiology, diagnosis, and appropriate management of the allergic rhinitis.
... He contrasted this to "immunity", which he explained as a protective reaction to a substance [36,37]. While allergies can cover a broad spectrum of response mechanisms (there are four different types in total) [37], in modern times, the term has come to be more associated with IgE-mediated allergic disease, which are the subject of this thesis [38]. ...
... Its symptoms include airway inflammation, mucus hyper secretion and airway hyper responsiveness [48]. Histamine blocker do not have a noticable effect on asthma [38], therefore other treatments, like corticosteroids are required. Allergic rhinitis is characterised by nasal congestion, sneezing and rhinorrhea, caused by the allergen provoking inflammation inside the nose [49]. ...
This thesis looks at development of acoustic devices that utilise ultrasound and its interaction with particles near surfaces. The devices are aimed at application in three fields: detection, diagnosis, and eradication. To capture pathogens and cells for capture, a thin-reflector device was combined with a specific antibody coating applied to the boundary between the reflector and fluid layers. The device was optimised and found to have a strong resonance that can push even small 1 µm sized objects to the surface to be captured. A suitable substitute in the detection experiments for anthrax was chosen in Bacillus globigii (BG) spores. They were stained with a fluorescent dye and used to find the limit of detection of the device. The system was also evaluated for the capture of basophils, providing insight into the possibilities of using the same device for allergy diagnosis. The aim was to capture as many basophils as possible in the shortest amount of time, all while maintaining ease of use. For biofilm eradication, a new device was constructed that can create ultrasonic travelling waves that push a microbubble and antibiotic solution into a biofilm, which was then analysed to find what proportion of bacteria survived. A variety of important parameters were considered and tested to find the optimal strategy for improving antibiotic performance with ultrasound stimulated microbubbles.
... The recognition that T h 2 inflammation is a part of the overarching type 2 inflammatory cascade and that type 2 inflammation is the predominant type of inflammation in atopic disorders is important because this type of inflammation can have different forms which may be triggered by things other than allergens, such as viruses, irritants, and pollutants [5][6][7]. Extrinsic forms, triggered by allergens, are typically associated with higher levels of serum immunoglobulin E (IgE) and allergen specific IgE [5]. Intrinsic forms, triggered by things other than allergens and less understood, are not associated with elevated IgE levels but present with clinical similar symptoms to the extrinsic form [5]. ...
... Regardless of the type of trigger, once the epithelial/ mucosal barrier is stimulated, these cells produce cytokines such as IL-25, IL-33, and thymic stromal lymphopoietin (TSLP) (Fig. 1) [6][7][8]. Both IL-25 and IL-33 can induce the production of type 2 cytokines, such as IL-4, IL-5, and IL-13, and IL-25 downregulates the production of IFN-γ [9,10]. ...
Purpose of the Review
This article provides a concise overview of important aspects of immunology related to atopic disorders and the key inflammatory components that biologic agents target.
Recent Findings
Over 15 years ago, the first biologic agent for an allergic disease gained FDA approval. Since then, additional attention has been given to elucidating the underlying pathways involved in these inflammatory disorders and identifying other potential targets that may be used to treat these conditions. In the last 5 years, not only have new biologic agents emerged to treat other atopic conditions, but also currently available agents have gained additional indications and even more unique biologic agents are in the research pipeline, currently undergoing Phase 2 and 3 trials. These agents provide the potential therapeutic option to treat multiple disorders with a single intervention and thus a familiarity with the immunology of allergic diseases as well as the aspects of the immune system that each biologic agent targets can aid the practitioner in selection of which agent to utilize.
Summary
The potential to select a biologic agent that targets a particularly inflammatory element and allows the practitioner to provide treatment for more than one atopic disorder is a very exciting prospect, indeed. Knowledge of the inflammatory cascade and, in particular, type 2 inflammation can assist in the selection of which agent or agents to consider using when treating these allergic diseases.
... Los países desarrollados y en vías de desarrollo se ven seriamente afectados cuando la enfermedad alérgica interfiere con el trabajo y la productividad, más aún si consideramos el alto costo de los medicamentos 8,9 . En personas genéticamente predispuestas a desarrollar enfermedades atópicas, los factores externos más importantes son la exposición a aeroalérgenos como pólenes, ácaros del polvo, esporas de hongos y epitelios de animales 10 . El tipo de sensibilización de una determinada población dependerá de la cantidad y tipo de aeroalérgenos presentes en el ambiente donde vive 10,11 . ...
... En personas genéticamente predispuestas a desarrollar enfermedades atópicas, los factores externos más importantes son la exposición a aeroalérgenos como pólenes, ácaros del polvo, esporas de hongos y epitelios de animales 10 . El tipo de sensibilización de una determinada población dependerá de la cantidad y tipo de aeroalérgenos presentes en el ambiente donde vive 10,11 . Así, en general, en localidades húmedas y costeras se desarrolla preponderantemente una sensibilización a ácaros del polvo 12 . ...
Background:
Allergic rhinoconjunctivitis (ARC) has a prevalence of 30% in industrialized countries. For an accurate diagnosis and treatment, it is crucial to identify the causative aeroallergen.
Aim:
To evaluate aeroallergen sensitization in adults with ARC in the city of Temuco, Chile.
Patients and Methods:
A skin test against the main aeroallergens present in Temuco was carried out in patients aged 15 to 64 years with ARC diagnosed by medical examination and the Score For Allergic Rhinitis.
Results:
At least one aeroallergen sensitization was present in 234 (62.4%) out of 375 patients. Pollen-sensitized patients were positive mainly for Grasses (44.4%), Plantago (27.8%), Cynodon (26.1%), Sorrel (23.5%), Birch (14.9%), Nothofagus obliqua (13.3%) and Alder (11.1%). Dust mites were the most common non-pollinic sensitizing aeroallergens, including Dermatophagoides pteronyssinus (70.1%) and Dermatophagoides farinae (62.8%).
Conclusions:
According to our results, skin tests in the city of Temuco should include at least dust mites, pollens of Grasses, Plantago, Cynodon, Sorrel, Birch, Nothofagus obliqua and Alder, because these allergens account for 93% of ARC cases in this city.
... Allergic disorders, including allergic rhinitis (AR), asthma, and atopic dermatitis (AD), are common diseases that affect more than 300 million people worldwide. [1][2][3] Although these allergic diseases are traditionally characterized by an overzealous Th2-mediated inflammatory response, it has become increasingly appreciated in recent years that group 2 innate lymphoid cells (ILC2s) play an important role in the initiation and orchestration of type 2 immunopathologies. 4,5 ILC2s are the innate counterparts of Th2 lymphocytes but lack rearranged antigen receptors. ...
Group 2 innate lymphoid cells (ILC2s) are key players in type 2 immunity, but whether they can be directly activated by microbial ligands remain uncertain. In this study, we observed a positive correlation between blood endotoxin (LPS) levels and circulating ILC2s in allergic patients. In vitro, LPS robustly induced ILC2 proliferation and production of type 2 effector cytokines. RNA-seq revealed a type 2 immune-responsive profile in LPS-stimulated ILC2s. Notably, ILC2s lost their LPS-mediated growth and activation capacity when treated with TLR4 receptor antagonists and inhibitors of the NF-κB and JAK pathways, though this effect was not observed with IL-33 receptor blocking antibodies. Genetically, ILC2s from TLR4 knockout (KO) mice, but not from ST2 KO mice, were unresponsive to LPS. Collectively, these findings suggest a direct, non-canonical activation mechanism of ILC2s via the LPS-TLR4-NF-κB/JAK signaling axis.
... These molecules promote class switching of antibodies produced against allergens, making B cells more sensitive to the allergen. [35] Immunoglobulin E antibodies play a central role in allergic reactions and are part of the body's response to allergens. These antibodies are critically important in sensitizing to allergens found particularly on mucosal surfaces such as the respiratory tract and digestive system, as well as on the skin. ...
An allergy occurs when the immune system reacts to substances that are typically harmless under normal circumstances. These reactions are triggered when antibodies respond specifically to these substances upon their entry into the body. Allergens such as pollen, dust, mites, and animal dander can be inhaled or ingested, such as food items. Symptoms of an allergic reaction may include hives, itching, allergic rhinitis, asthma, sneezing, runny nose, and nasal congestion. Removing or avoiding contact with the allergen can often resolve these symptoms. Allergies vary widely among individuals, manifesting differently in different age groups and affecting various parts of the body with varying severity. For instance, one person exposed to an allergen might experience nasal congestion, while another might suffer from sweating and itching. During an allergic response, T cells produced by our body come into play. T cells, a subset of lymphocytes, play a crucial role in the immune response by activating other immune system cells against foreign allergens. This review aims to provide an overview of the relationship between allergies and T cells.
... The subsequent binding of allergens to IgE causes the crosslinking of IgE-FCε complexes, releasing histamines, leukotrienes, and other inflammatory mediators through degranulation [3,4]. The uncontrolled release of inflammatory cytokines, interleukins, interferons, and chemokines causes allergic reactions, leading to sneezing, runny nose, itching, watery eyes, and swelling [5]. Pathways like Toll-like receptor signaling, FCε-RI signaling, histamine metabolism and degradation, and arachidonic acid metabolism play crucial roles in allergic rhinitis development [6][7][8][9]. ...
... Allergy results from an exaggerated immune response to harmless environmental substances called allergens, leading to a range of allergic reactions from mild to severe. 1 Allergic diseases vary in severity, from mild symptoms to life-threatening reactions, 2 and their increasing prevalence in recent decades poses a significant public health concern. 3 Allergic diseases are showing an alarming trend of increasing severity, 4 with conditions like asthma, rhinitis, and dermatitis becoming more prevalent and severe. ...
Background:
Allergic diseases are a growing public health concern with increasing prevalence and severity. Allergens play significant roles in triggering immune responses and the development of allergic reactions.
Objective:
Investigate the presence and clinical significance of dust mites, storage mites, and predatory mite Cheyletus eruditus(Ce) in household environments.
Methods:
A survey of household dust was performed to determine mite occurrence and analyze influencing factors, an analysis of the correlation between mite species and allergic symptoms, and basophil activation triggered by mite allergens. Cross-reactivity between Ce and house dust mites was assessed.
Results:
The high appearance rate of mite species in households of Taiwan was Dermatophagoides pteronyssinus (Dp) and D. farinae(Df). Environmental factors such as pet keeping, vacuum cleaner usage, air conditioner usage, proximity to the kitchen, cleaning frequency, and protein concentration in beds were shown to influence mite prevalence. The appearance of Dp and Df significantly increased the occurrence of airway and nasal symptoms, while the presence of Ce was strongly correlated with skin symptoms. The activation of basophils and the correlation between specific IgE levels and allergic symptoms in response to Ce exposure were demonstrated. The presence of Ce was associated with elevated levels of allergens in bedding. The IgE adsorption between mite species was demonstrated suggesting cross-reactivity between the Ce and Dp was limited. Presence of Ce is associated with elevated levels of major mite allergens in beddings.
Conclusion:
Allergenicity of Ce was confirmed by IgE reactivity and basophil activation regarding mite infestation as a potential cause of skin-related allergy.
... The allergic reaction can occur within minutes or an hour. It would result in an acute, sharp response depending on the type and quantity of allergens introduced into the system [2]. Anaphylaxis is a severe hypersensitivity reaction that occurs in allergy-prone patients, which leads to the large production of histamine in a short time interval from the body's mast cells. ...
We propose an IoT-enabled miniaturized remote auto-injector supported by smartwatch health monitoring for the emergency medical treatment of allergy-induced anaphylaxis patients. A smartwatch monitors the patient's vital biomarker data (heart rate, oxygen saturation, and fall detection), which are sent in real-time to a local server or cloud. Upon identification of the risk of anaphylaxis, the auto-injector device worn by the patient is actuated wirelessly to instantly inject an epinephrine emergency dose to save the patient's life by restoring cardiac rhythm and controlling mucosal congestion, glaucoma, and asthma. In the meantime, a physician or care provider can monitor the patient's status in real-time. The auto-injector consists of two shape memory alloy (SMA) actuators injecting and retracting a subcutaneous injection needle and connected to an in-house developed micropump loaded with epinephrine. The system's response time is 3 seconds, whereas the needle penetration and drug injection are completed in 15 seconds. Epinephrine dosage can be injected at a maximum flow rate of 2524 μl/min against a maximum of 14 kPa backpressure. The system features a novel feature by retracting the needle immediately after the injection to avoid the patient's injury. Furthermore, the SMA actuation force and system package can be adapted for instant intramuscular injection; meanwhile, the needle retraction feature prevents skin and muscle injury.
... Allergic disorders including asthma, allergic rhinitis and atopic dermatitis (AAA) are common diseases affecting more than 300 million people worldwide [1][2][3] . Although AAA diseases are traditionally characterized by an overzealous Th2-mediated inflammatory response, it has become increasingly appreciated in recent years that group 2 innate lymphoid cells (ILC2) play an important role in the initiation and orchestration of type 2 immunopathologies 4 . ...
Group 2 innate lymphoid cells (ILC2) play a critical role in type 2 immunity. Although their classical activators are known to be host epithelial-derived alarmin cytokines released from tissue damage at barrier sites during microbial infections and allergen exposures, it remains elusive whether ILC2 cells can be directly activated by microbial ligands. Here we examined a number of microbial ligands and identified lipopolysaccharides (LPS) from multiple species of Gram-negative bacteria potently stimulated the cultured human ILC2 to proliferate and produce massive amounts of type 2 effector cytokines IL-5 and IL-13. RNA-seq data revealed a remarkably similar set of type 2 immune responsive genes induced by LPS and IL-33. However, blocking IL-33 receptor signaling failed to decrease the effects of LPS. In contrast, blocking TLR4 receptor, NF-kB and JAK pathways completely abolished the growth and function of LPS-treated human ILC2. Furthermore, ILC2 cells of TLR4 deficient mice were unable to respond to LPS treatment in vitro and in vivo. Importantly, patients with allergic rhinitis, atopic dermatitis and bacteremia had an increased number of peripheral blood ILC2 cells that correlated with elevated serum endotoxin. Collectively, these findings support a non-canonical mode of direct activation of human ILC2 cells via the LPS-TLR4-NF-kB/JAK signaling axis, which is independent of the classical IL-33-ST2 pathway. Thus, targeting TLR4 signaling pathway might be developed as an alternative approach to treat microbial infection-associated and ILC2-mediated inflammatory conditions.
... Asthma in adulthood is less likely to be associated with allergens and appears to be more frequent in women rather than men [7]. Usually, adulthood asthma is hard to be treated and shows persistent resistance to efficient conventional treatments of childhood asthma [7,8]. ...
Background
Gasdermin A (GSDMA) and gasdermin B (GSDMB) have been associated with childhood and adult asthma in many populations including the Jordanian population. It is also known that IgE plays a crucial role in various allergic disorders, such elevated levels of total serum IgE were detected in asthma and allergic rhinitis. IgE immunoglobulin is responsible for the release of numerous inflammatory mediators, such as histamine and prostaglandins, from mast cells in asthmatic patients.
Objective
In this study, single nucleotide polymorphisms of GSDMA (rs7212938, T/G) and GSDMB (rs7216389, T/C) in Jordanian population were investigated for their association with total IgE levels in serum of asthmatic children and adult subjects.
Methods
The genetic polymorphism analysis for SNPs was performed using the polymerase chain reaction (PCR)/restriction fragment length polymorphism method (RFLP). Three analysis models were applied to the genotype data: co-dominant, dominant and recessive.
Results
Our data demonstrate a significant correlation between GSDMB genetic SNP (rs7216389) and the total IgE serum level. Where one minor allele in the GSDMB gene is sufficient to induce significant changes in the IgE serum levels and plays a role in the pathogenesis of asthma in asthmatic children of the Jordanian population. Suggesting that this polymorphism might have a protective effect against asthma risk. While the presence of the GSDMB polymorphism alone might not be sufficient to associate with the high risk of developing asthma or responding to it in adults in Jordanian population.
Conclusion
In conclusion, the current study confirms the significant association of GSDMB genetic SNP (rs7216389) with IgE levels in asthma patients in Jordanian population, while no significant correlation of GSDMA and IgE level was found in both child and adult asthmatic patients.
... The relationship between allergic IgE-mediated reaction and the eosinophilic trait is one of the most accepted dogma in immunology. 29 Our finding showing prominent eosinophilic inflammation in atopic asthma does not come as a surprise. It should, however, be noticed that more than half of atopic asthmatics still exhibited sputum eosinophils below 3%, thereby qualifying as non eosinophilic asthma. ...
Background
Atopic asthma is one of the most common asthma phenotypes and is generally opposed to the non-atopic counterpart. There have been very few large-scale studies comparing atopic and non-atopic asthmatics in terms of systemic and airway inflammation across the age spectrum.
Methods
Here, we have undertaken a retrospective study investigating 1626 patients (924 atopic and 702 non-atopic asthmatics) recruited from our university asthma clinic who underwent extensive clinical investigations including induced sputum. Atopy was defined by any positive specific IgE to common aeroallergens (>0,35 kU/L). We performed direct comparisons between the groups and sought to appreciate the influence of age on the airway and systemic inflammatory components. The study was approved by the ethics committee of the University Hospital of Liege (Ref. 2016/276). Informed consents were obtained from healthy subjects.
Results
Atopic asthmatics were younger (P < .001), had a higher male/female ratio (P < .001), an earlier disease onset (P < .001) and a greater proportion of treated rhinitis (P < .001) while non-atopic asthmatics had greater smoke exposure (P < .001), lower FEV1/FVC ratio (P = .01) and diffusing capacity (P < .001). There was no difference between the 2 groups regarding FEV1 (% predicted), asthma control, asthma quality of life and exacerbations in the previous 12 months. Regarding inflammation, atopic patients had higher FeNO levels (median = 28 ppb, P < .001), were more eosinophilic both in blood (median = 2.8%, P < .001) and in sputum (median = 2.2%, P < .001) while non-atopic patients displayed greater blood (median = 57%, P = .01) and sputum (median = 58.8%, P = .01) neutrophilic inflammation. However, stratifying patients by age showed that non-atopic asthmatics above 50 years old became equally eosinophilic in the sputum (P = .07), but not in the blood, as compared to atopic patients. Likewise, FeNO rose in non-atopic patients after 50 years old but remained, however, lower than in atopic patients.
Conclusions
We conclude that, while sharing many features, atopic group still differentiates from non-atopic asthmatics by demographics, functional and inflammatory profiles. When atopic asthmatics showed a constant eosinophilic pattern across the age spectrum, non-atopic asthmatics were found to be neutrophilic before the age of 50 but eosinophilic above 50 years old.
... This discovery has led us to discover many effective treatment methods for diseases. IgE antibodies are generally produced as a response to allergens entering the body [15]. But this protective response doesn't always happen as a re3sponse to environmental allergens, but in people with a genetic predisposition called Atopy, the body starts developing IgE antibodies when exposed to harmless allergens, hence creating a severe allergic reaction from excess buildup of IgE antibodies [16]. ...
Introduction: Bronchial asthma is a medical condition that causes a deformity in the airway path of the lungs, causing them to swell and get narrow. The swelling produces excess mucus in the pathway, making it hard to breathe, and this results in coughing, short breath, and wheezing. This is often caused by allergic reaction to outside stimulants. The allergic reaction causes the body to produce Immunoglobin E antibodies that help the immune system fight back against allergens, but excess production of IgE can lead to severe allergic reaction and respiratory difficulties. Aim of the study: The aim of the study was to observe the IgE levels of Bronchial Asthma patients. Methods: This was a prospective cross-sectional study was conducted in the Department of Medicine, Mainamoti Medical College Hospital, Cumilla, Bangladesh during the period from January 2020 to July 2020. Fifty-three (53) patients were selected maintain inclusion criteria. Proper written consents were taken from all the participants before starting data collection. A pre-designed questionnaire was used in patent data collection. All data were processed, analyzed and disseminated by MS Office and SPSS version as per needed. Result: The present study had 53 participants in total. 45.28% of the participants were aged between 41-60 years, and 32.08% were aged between 21-40 years. 34% were male and 66% were female, and the male: female ratio was 1:1.95. 49 participants were diagnosed with bronchial asthma while 4 did not have asthma. 30.19% had mild asthma with Mean±SD IgE of 464.000±57.10, 26.42% had moderate asthma and Mean±SD IgE of 695.410±82.09, and 35.85% had severe asthma with Mean±SD IgE of 1045.320±14.16 IU/ml. Conclusion: The study found that asthma can be different according to age, and older women have a higher prevalence of asthma, compared to older male population. IgE levels of above 100 IU/ml can be abnormal, and according to WHO guidelines, IgE levels of >150 can be considered as an ......
... Effector cells (i.e., mast cells, basophils, and precisely, eosinophils) release additional inflammatory mediators and cytokines, continuing the proinflammatory response which results in the induction of hyper-IgE, eosinophil survival, and mucus hyperproduction; and interact with bronchial epithelial cells, smooth muscle cells, and keratinocytes, by reason of their activation and apoptosis (Fig-2). This phase is responsible for the symptoms of allergic diseases, and constant exposure to the allergen causes disease chronicity (Kay et al. 2001;Calzada et al. 2018). ...
Allergens can elicit immunotoxic effects in humans. It is often life-threatening and severe that influences the prevalence and course of allergic diseases like asthma, allergic rhinitis, atopic dermatitis, and contact dermatitis. Genetic as well as environmental factors may contribute to allergy and related physiological responses. The pathogenesis of asthma and allergy involves the interaction of genetic markers and environmental factors. Various toxic compounds like metals, foods, even certain kinds of drugs can elicit immunotoxicity. Asthma is subjected to inflammation of the airways; of which genes and environment both are responsible in an interactive way. The innate immunity genes particularly CD 14 and Toll like receptors TLR4 and TLR 2 play an important role on susceptibility to asthma and allergy. The genes interrelated to asthma have been found through Single Nucleotide Polymorphism (SNP) studies. There are other risk factors associated with allergic diseases which require long-term, effective therapeutic approaches as a treatment regimen. The present study is an attempt to highlight the immunological reactions of certain compounds and gene-environment interplay in developing the pathological symptoms associated with asthma.
... AR is characterized by episodes of sneezing, itching, rhinorrhea, and nasal obstruction [34]. It is caused by immunoglobin E-mediated reactions against inhaled allergens. ...
The human airway is protected by a defensive mucus barrier. The most prominent components of mucus are the mucin glycoproteins MUC5AC and MUC5B. They are produced by goblet cells and submucosal gland cells in the upper and lower airways. Hyperplasia of these cells and hypersecretion of MUC5AC and MUC5B characterize chronic inflammatory diseases of the upper and lower airways. Recent studies have revealed that MUC5AC and MUC5B are expressed at specific sites in the respiratory tract through different molecular mechanisms and have distinct functions. Morphometric and histochemical studies have also examined the roles of goblet cells, submucosal gland cells, MUC5AC, and MUC5B in different chronic airway diseases individually. The individual study of goblet cells, submucosal gland cells, MUC5AC, and MUC5B in airway diseases would be helpful for precisely diagnosing chronic inflammatory diseases of the airway and establishing optimal treatments. This review focuses on the distinct secretion of MUC5AC and MUC5B and their producing cells in chronic inflammatory diseases of the upper and lower airway.
... Inflammation of a submucosa appears to predominate in the large airways, whereas inflammation in the small airways mostly occurs beyond the bronchial smooth muscle [28]. Further, Th type-2 (Th2) type of inflammation found in chronic allergic inflammatory reactions at numerous tissue sites is typical in patients with asthma who frequently have comorbidities including chronic rhinitis, sinusitis, atopic dermatitis, and food allergies [29]. While there is still controversy regarding the actual contribution of particular types of cells in all these other diseases, a consistent trend is emerging, particularly in asthmatic inflammation with an allergic component. ...
Asthma is among the world's most common severe lung disorders, affecting one-third of the world's population with incidence ranging from 4.9% to 12.7%. Around 3.5 million people die annually due to the worse health effects of asthma. Men (6.2%) have been seen to be less prevalent than women (10.4%) internationally. As a
product of inflammation and super sensitivity, asthma is a multifactorial condition with symptoms such as cough, shortness of breath, wheezing, and chest pain. There are a number of agents that may be responsible for the development of asthma. This includes air pollution, obesity, bacteria, viruses, fungi, flu germs, dust, pollen, tobacco, smoking, exercise, depression, anxiety, allergic agents, physical and emotional stress. Depending on the susceptibility of the individual, asthma showed mild to serious results. For a deeper understanding of disease pathogenicity, mechanistic mechanisms should concentrate on a number of aspects like metabolic abnormalities, molecular genetics, inflammatory asthma complexity, etc. Commensal micro biota is one of the main factors that cures disease and has a major role in balancing the immune system in the gut and lung. In addition to the foregoing, potential indicators include serum IgE, a
number of bloodstream eosinophil or levels of sputum eosinophil, FeNO (fractional exhaled nitric oxide), and serum periostin are presently employed in the asthma diagnosis. The two key therapies available on the basis of disease severity for patients
are oral corticosteroids and bronchodilators. However, steroid-based therapy has certain side effects, such as elevated BP, adrenal suppression, and bone weakening. Due to this, we should target non-steroid medications, including anti-cholinergic medication (Tiotropium) and biological therapy. For serious asthma patients, various new medications (such as Anti-IL-4, Anti-IL-5, Anti-IL-13, and Anti-IgE therapy) have been used and found effective To select the right medication and system for a better treatment plan, asthma patient requires proper review such as guidance, constancy, advice, drug alert, refill warning, notification warning, etc.
Keywords: Allergy, Anti-Cholinergic, Asthma, Biomarkers, Bronchodilators, Corticosteroids, Immunesystem, Inflammation, Micro biota, Wheezing.
... Dermatitis offers a wide clinical picture ranging from minor to major forms with erythematous rash 2 . Cardinal features of itchy inflammation of skin (eczema) are redness, eruptive skin lesions, papules which go along with an intense pruritus and cutaneous hyperreactivity 3 . Atopic dermatitis can be distinguished with cracked or scaly skin, discolored patches, red skin, papules, oozing from lesion, and intense itching, which can secondarily cause disturbed and hamper the quality of life. ...
Twak has intimate relationship with the Doshas, Sparsnendriyaas a whole is considered as Vatasthana. Twak and Rasadhatu are considered as Bahya Rogmarg. Eczema is widely considered to be specific type of Kushtha known as Vicharchika, with complex pathology, varying presentations, and various treatment modules within the context of Ayurveda. The Kushtha is generally used as a universal term for all kinds of skin disorders, which is further classified in two divisions i.e. Mahakushta and Kshudrakushta and Vicharchika is mentioned under Kshudrakushta. Vicharchika is considered as Rakta Pradoshaja Vikaras. Recurrences and chronic course is a distinct feature for this disease. Eczema is primarily managed with top-ical steroids, antiseptic, immune-suppressors drugs to inhibit immune and inflammatory response. Howev-er, it does not provide treatment for the root causative factors. Ayurveda provides principle-based treatment for eczema by cleansing vitiated Dosha and balancing the Dosha and Dhatus. The case report involved a female patient of Pitta-Kaphaj Prakruti with exudate, intense itching, and erythema of the skin.Within one month of the beginning the treatment, eczematous lesions were improving and even after two months, the patient showed no signs of recurrence.
... e activation of mast cells by SARS-CoV-2 infection can worsen asthma control in several ways. Mast cell-derived mediators, mainly histamine, leukotrienes, PGD 2 , PGE 2 , tumor necrosis factor (TNF), thymic stromal lymphopoietin (TSL), and tryptase, induce the classic features of early asthmatic reaction in vivo, therefore inducing bronchoconstriction, mucosal edema, and mucus hypersecretion and hence the observed worsening of asthma control in a subset of asthmatics infected with SARS-CoV-2 [128,130,131]. ...
Asthmatics are at an increased risk of developing exacerbations after being infected by respiratory viruses such as influenza virus, parainfluenza virus, and human and severe acute respiratory syndrome coronaviruses (SARS-CoV). Asthma, especially when poorly controlled, is an independent risk factor for developing pneumonia. A subset of asthmatics can have significant defects in their innate, humoral, and cell-mediated immunity arms, which may explain the increased susceptibility to infections. Adequate asthma control is associated with a significant decrease in episodes of exacerbation. Because of their wide availability and potency to promote adequate asthma control, glucocorticoids, especially inhaled ones, are the cornerstone of asthma management. The current COVID-19 pandemic affects millions of people worldwide and possesses mortality several times that of seasonal influenza; therefore, it is necessary to revisit this subject. The pathogenesis of SARS-CoV-2, the virus that causes COVID-19, can potentiate the development of acute asthmatic exacerbation with the potential to worsen the state of chronic airway inflammation. The relationship is evident from several studies that show asthmatics experiencing a more adverse clinical course of SARS-CoV-2 infection than nonasthmatics. Recent studies show that dexamethasone, a potent glucocorticoid, and other inhaled corticosteroids significantly reduce morbidity and mortality among hospitalized COVID-19 patients. Hence, while we are waiting for more studies with higher level of evidence that further narrate the association between COVID-19 and asthma, we advise clinicians to try to achieve adequate disease control in asthmatics as it may reduce incidences and severity of exacerbations especially from SARS-CoV-2 infection.
... However, few review papers have focused on the relationships between the bioactive compounds of C. militaris and immunomodulation, despite the importance of this topic (Zhang et al., 2020b). The balanced interplay between type 1 and type 2 immunity is crucial to health (Bieber, 2008;Kay, 2001a, Kay, 2001bLloyd andSnelgrove, 2018, McInnes andSchett, 2011;Moutsopoulos et al., 2017). For example, autoimmune diseases (e.g., rheumatoid arthritis) are related to stronger type 1 immunity, and atopic diseases (e.g., asthma, atopic dermatitis, and allergic rhinitis) are associated with stronger type 2 immunity. ...
Cordyceps militaris (C. militaris) is a fungus with a long history of widespread use in folk medicine, and its biological and medicinal functions are well studied. A crucial pharmacological effect of C. militaris is immunomodulation. In this review, we catalog the immunomodulatory effects of different extracts of C. militaris, namely total extracts, polysaccharides and cordycepin. Total extracts obtained using water or 50% ethyl alcohol and polysaccharides from C. militaris were discovered to tend to promote type 1 immunity, whereas total extracts obtained using 70-80% ethyl alcohol and cordycepin from C. militaris were more likely to promote type 2 immunity. This article is the first to classify the immunomodulatory effects of different extracts of C. militaris. In addition, we discovered a relationship between different segments or extracts and differing types of immunity. This review can provide the readers a comprehensive understanding on the immunomodulatory effects of the precious folk medicine and guidance on its use for both health people and those with an immunodeficiency.
... Therefore, the adverse health impact of 'diesel fuel exhaust particles' (DEPs) have been a great source of public concern (Konur 2021ac-ad). In this context, the causation of respiratory illnesses (Ashbaugh et al., 1967;Eder et al., 2006;Force et al., 2012;Kay, 2001;Wills-Karp et al., 1998) by DEPs in humans has been studied more extensively (Konur, 2021ac-ad). ...
... (81) Moreover, B cell proliferation and stimulation, particularly naïve and transitional B cell with T-independent development can be achieved by a combination of 10 herbal components from Astragalus membranaceus Radix, Glycyrrhiza uralensis Radix, Phytophthora cinnamomi Cortex, Rehmannia glutinosa Radix, Paeonia lactiflora Radix, Cnidium cnidiifolium Rhizoma, Atractylodis lanceae Rhizoma, Angelica archangelica Radix, Panax ginseng Radix and Poria cocos (known as Juzen-Taiho-To, 十全大补汤, TJ-48). (82,83) T-dependent B cell terminal maturation and class switching recombination also were assigned as the function of 8 medical plants, Astragalus membranaceus Radix, Atractylodis lanceae Rhizoma Alba, Panax ginseng Radix, Angelicae gigantis Radix, Citri unshius Pericarpium, Glycyrrhiza uralensis Radix et Rhizoma, Actaea racemosa Rhizoma, and Bupleurum chinense Radix (known as Bu-Zhong-Yi-Qi-Tang, 补中益气汤, TJ-41). (84) Immunological promotion of TCMs on humoral immunity using cytokine production were evident using TJ-48, (85) Sho-Saiko-To (小柴胡 汤, TJ-9, Bupleurum falcatum Radix, Pinellia ternata Rhizoma , Scutellaria baicalensis Radix , Panax ginseng, Ziziphus mauritiana, Glycyrrhiza glabra, and Zingiber officinale), (86) and Ninjin-Yoei-To (人参 养荣汤, NYT, Paeonia lactiflora Radix, Aralia elata Radix, Citrus unshiu peel, Astragalus propinquus Radix, Cinnamomum verum Cortex, Panax ginseng, Atractylodes lancea Rhizoma, Glycyrrhiza glabra, Rehmannia glutinosa Radix, Schisandra chinensis fruit, Poria sclerotium, and Polygala vulgaris Radix). ...
The human immune system represents a dynamic multiscale system with high complexity in biology. Humoral immunity, as the main branch of adaptive immunity, is characterized by differentiated stages of the B lymphocytes, producing the final product of antibodies that has a diversity of the tuning mechanisms within genetic and epigenetic levels in confrontation with environmental exposures. Disorders because of disturbed humoral immunity are linked with dysregulation of feedback-regulated signaling and the dynamic of immune components that determine the overall response. Food products, mainly herbal components have a significant role in tailoring the immune system micro-ecosystem which can diversify the adaptive nature of humoral immunity. Herein, we review the current evidence-based approaches for the impact of medicinal herbs on humoral immunity signaling and antibody production with a focus on immunotherapeutic applications.
... ECP has been observed to influence some cell types present in the respiratory tract. Accumulation and infiltration with eosinophils (EG2 + ) have been observed in bronchial biopsies of asthma, rhinitis, and cutaneous responses after an antigen challenge in atopic individuals [43]. ...
Allergic asthma (AA) is a complex disorder with heterogeneous features of airway hyperresponsiveness, inflammation, and remodeling. The increase of airway smooth muscle (ASM) mass is a fundamental component of bronchial remodeling in AA, yet the pathophysiological mechanisms and clinical outcomes associated with ASM modulation are still elusive. The objective of this study is to compare the expression level of β-dystroglycan (β-DG) in ASM in AA subjects and a healthy control group and to investigate the relationship between eosinophils and β-DG in ASM in patients with AA. Thirteen AA patients and seven control subjects were analyzed for the ASM area and eosinophil cells. Bronchial biopsies were stained by β-DG and eosinophil cationic protein (ECP) using immunohistochemistry. The proportion of ASM with β-DG staining was greater in those with AA than in the healthy control group (mean (95% CI) (28.3% (23.8–32.7%) vs. 16.4% (14.1–18.5%), P < 0.0001). The number of ECP positive cells was higher in patients with AA than in the control group (4056 (3819–4296) vs. 466 (395–537) cells/mm ² P < 0.0001). In AA, the number of ECP positive cells was significantly correlated to the β-DG expression in ASM ( r = 0.77, P = 0.002). There is an increased β-DG expression in ASM and a higher number of ECP positive cells in the bronchial biopsy of those with AA than those in the control group. The increased expression of β-DG in ASM in AA subjects correlates with the number of eosinophils, suggesting a role for this cell in airway remodeling in AA.
... The presence of fungal spores in indoor buildings is well known due to its consequences for human health (Crawford et al. 2015;Kim et al. 2018; Portnoy et al. were from cosmopolitan genera such as Aspergillus/ Penicillium and Cladosporium, the most common High quantities of Aspergillus/Penicillium during all the stored period were identified in the cooling system warehouse when comparing with the ambient air system, differentiating both environments. Penicillium is the most prevalent airborne mold type in all regions being common in damp materials in damp indoor environments (Kay 2001;Adnan and Samsong 2011). In this study had been observed mould-fungi colonies in the wood boxes used to store potatoes. ...
Potatoes production is the main source of income in A Limia (Northwest Spain). Most of the potatoes harvest is stored in piles in farmer´s warehouses without systems to control temperature and relative humidity and only a few industries have storage facilities with cooling systems. This study constitutes an approach to detecting fungal spores present inside potato warehouses and the influence of the environmental conditions on the prevalence of the different types of fungi. The most common spores were Cladosporium and Aspergillus/Penicillium representing more than 94% of the identified spores of fungi. However, some potential fungal potato pathogens such as Alternaria, Helminthosporium, Fusarium and Phytophthora were also detected. In the warehouse without control of the storage conditions, the most represented fungal spores were from Cladosporium followed by Aspergillus/Penicillium, Helminthosporium and Alternaria whereas during storage with cooling conditions, the most abundant were Aspergillus/Penicillium, Cladosporium, Fusarium, Helminthosporium and Leptosphaeria. The results showed a close relationship between the storage conditions and the levels of some identified fungi. The low representation of pathogenic fungi Alternaria and Helminthosporium stood out in the facilities with cooling systems. Monitoring of airborne elements during potato storage could be useful tool for detecting the presence of potato pathogens in the environment and taking management decisions to avoid economic losses.
... Dysfunction of many of the same cells and inflammatory mediators are involved in the pathogenesis of allergy [17][18][19][20][21][22]. However, there have been limited studies investigating how allergy may be related to infertility and those that have been performed have yielded inconsistent results. ...
Objective:
Assisted reproductive technologies (ARTs) are complex processes with multiple and diverse opportunities for human error. Errors in ART are thought to be rare, but can have devastating consequences for patients and their offspring. The objectives of this article are to review known cases of human error in the ART laboratory and suggest preventative strategies.
Methods:
We performed a systematic review of the literature in accordance with Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines using PubMed and Google Scholar databases. Studies were eligible for inclusion if they involved known cases of unintentional human error in the ART laboratory. Only full-text articles in English were included. References of the resulted studies were considered for inclusion.
Results:
A total of 420 articles were screened and 37 articles were selected for inclusion. These largely included case reports and reviews in the medical and legal literature. Twenty-two adverse events due to human error in the ART laboratory were identified. Eight of these adverse events were the result of the insemination with the wrong sperm, 6 errors lead to the transfer of the wrong embryo, 3 lead to an error in preimplantation genetic testing, and 5 adverse events lead to the failure of gamete and embryo cryostorage.
Conclusions:
Since the advent of ART, there have been reports of catastrophic events occurring secondary to human error in the laboratory to include incidents of unintended parentage, and have resulted in the loss of embryos and gametes through cryostorage failure. Proposed solutions include the stringent implementation and adherence to safety protocols, adequate laboratory staffing and training, and novel methods for specimen labeling and tracking. Of utmost importance is having knowledge of these errors and the ability to determine cause so that future events can be prevented.
... Kay in 1987 described allergic rhinitis as an IgE mediated hypersensitivity disease of mucous membrane of nasal airway characterized by sneezing, nasal discharge and blockage. 32 Wilson et al demonstrated that histamine provocation of nasal mucosa produces reflex sneezing and marked vasodilation via both H 1 and H 2 receptors in allergic rhinitis. 33 There is significant basal levels of free histamine which is between 14 to 65 ng/ml in patients with allergic rhinitis whereas in controls it is 10. ...
Ascorbic acid plays a pivotal role in common cold and allergic rhinitis by affecting the innate and adaptive immunity It antagonizes mediators of allergic rhinitis like histamine, prostaglandins etc. It also maintains the normal redox potential of the cells preventing bonding of antibody to antigen. It helps in stress conditions and has stimulatory effect on interferon synthesis. The present study was undertaken to study the role of plasma ascorbic acid in patients suffering from nasal allergy.
... However, few review papers have focused on the relationships between the bioactive compounds of C. militaris and immunomodulation, despite the importance of this topic (Zhang et al., 2020b). The balanced interplay between type 1 and type 2 immunity is crucial to health (Bieber, 2008;Kay, 2001a, Kay, 2001bLloyd andSnelgrove, 2018, McInnes andSchett, 2011;Moutsopoulos et al., 2017). For example, autoimmune diseases (e.g., rheumatoid arthritis) are related to stronger type 1 immunity, and atopic diseases (e.g., asthma, atopic dermatitis, and allergic rhinitis) are associated with stronger type 2 immunity. ...
Cordyceps militaris (C. militaris) is a fungus with a long history of widespread use in folk medicine, and its biological and medicinal functions are well studied. A crucial pharmacological effect of C. militaris is immunomodulation. In this review, we catalog the immunomodulatory effects of different extracts of C. militaris, namely total extracts, polysaccharides and cordycepin. Total extracts obtained using water or 50% ethyl alcohol and polysaccharides from C. militaris were discovered to tend to promote type 1 immunity, whereas total extracts obtained using 70–80% ethyl alcohol and cordycepin from C. militaris were more likely to promote type 2 immunity. This article is the first to classify the immunomodulatory effects of different extracts of C. militaris. In addition, we discovered a relationship between different segments or extracts and differing types of immunity. This review can provide the readers a comprehensive understanding on the immunomodulatory effects of the precious folk medicine and guidance on its use for both health people and those with an immunodeficiency.
... 41 Environmental exposures dramatically influence the phenotype of allergic diseases, including atopic eczema, FA, asthma, and allergic rhinitis. [42][43][44][45] Mechanisms linking air pollutants such as particulate matter, NO 2 , and ozone to the development and exacerbation of asthma include the induction of both eosinophilic and neutrophilic inflammation driven by stimulation of airway epithelium and increase of proinflammatory cytokine production, oxidative stress, and DNA methylation changes. Although exposure during fetal development is often reported as a crucial time frame, exposure to air pollution is detrimental to anyone of any age, thus, influencing asthma onset and increase in asthma prevalence, mortality, persistence, and exacerbation. ...
Objective
The origin of allergic disease has traditionally been explained by IgEmediated immune responses to account for asthma, atopic dermatitis, atopic rhinitis, and food allergy. Research insights into disease origins support broader array of factors that predispose, initiate, or exacerbate altered immunity in allergic diseases: inherent epithelial barrier dysfunction, loss of immune tolerance, disturbances in gut and organ-specific microbiomes, diet, and age. Here, we discuss these influences that together form a better understanding of allergy as a systems disease.
Data Sources
We summarize recent advances in epithelial dysfunction, environmental influences, inflammation, infection, alterations in specific microbiome, and inherent genetic predisposition.
Study Selections
We performed a literature search targeting primary and review articles.
Results
We explored microbial-epithelial-immune interactions underlying the early-life origins of allergic disorders, and examined immune mechanisms suggesting novel disease prevention or intervention strategies. Damage to epithelial surfaces lies at the origin of various manifestations of allergic disease. As a sensor of environmental stimuli, the epithelium of the lungs, gut, and skin is impacted by an altered microbiome, air pollution, food allergens in a changed diet, and chemicals in modern detergents. This collectively leads to alterations of lung, skin, or gut epithelial surfaces, driving a type-2 immune response that underlies atopic diseases. Treatment and prevention of allergic diseases include biologics, oral desensitization, targeted gut microbiome alterations, and changes in behavior.
Conclusion
Understanding the spectrum of allergy as a systems disease will allow us to better define the mechanisms of allergic disorders and improve their treatment.
... Interfering with these tissue-specific homing receptors could be beneficial for patients with Th cell-mediated inflammatory diseases. Human CLA + Th2 cells are abundantly present in lesional skin of atopic dermatitis (AD) patients and allergen-specific Th2 cells induce AD inflammation [18][19][20]. However, it has been reported that mouse Th2 Fig. 1. ...
Naive Th cells, bearing receptors for cutaneous antigens, become activated in skin‐draining lymph nodes and express cutaneous lymphocyte antigen (CLA), which confers to these cells the capacity to migrate into the skin to exert their normal effector functions. In the case of atopic dermatitis (AD), allergen‐specific Th2 cells generate exacerbated responses and induce skin inflammation. In such a situation, interfering with the specific mechanism of skin homing would provide a therapeutic benefit. Here we report that CLA⁺ Th2 memory cells, derived from skin lesions of AD patients, selectively migrate to human skin grafts transplanted onto SCID mice in response to CCR4 but not CCR3, CCR8 or CXCR3 ligands. Skin homing of human CCR4⁺ Th2 memory cells was Pertussis toxin sensitive and restricted to the CLA⁺ subset. Furthermore, treatment of these mice with anti‐E‐selectin monoclonal antibody was sufficient to prevent CCL22‐mediated Th2 cell migration to human skin, which both, validates the model and highlights the importance of CLA/E‐selectin interactions in the homing process of Th2 cells to the skin. Using this mechanistic model we demonstrate that skin homing of human Th2 memory cells can be efficiently suppressed using a low molecular weight E‐selectin antagonist, which is of clinical relevance for the treatment of inflammatory skin diseases, including AD.
... In patients treated by SCIT for several years, the level of antigenspecific IgE antibody decreased, and that of IgG, especially IgG4, was increased in sera (31)(32)(33) . Regarding changes in antibodies by ILIT in this study, antigen-specific IgE and IgG antibody production increased and decreased, respectively. ...
Background:
Intralymphatic immunotherapy (ILIT) for allergic patients requires only a few intralymphatic injections of the allergen. However, the effectiveness and safety for Japanese cedar pollinosis are unclear. The objectives of this study were to clarify whether and how long ILIT is effective for pollinosis, and its safety.
Methods:
In an open pilot investigation followed by a double-blind, placebo-controlled study, patients with Japanese cedar pollinosis received 3 intralymphatic inguinal injections of the pollen extracts before the first pollen season. The symptom medication score (SMS), nasal provocation testing and scoring visual analogue scale (VAS) were assessed after the first-third seasons.
Results:
(1) Although mild adverse events were induced at the injected site, severe adverse events were not noted. (2) During the latter part of the first season, ILIT-treated patients (n=12) tended to show improved SMS compared to placebo-treated (n=6) without statistical significance. When assessed by nasal provocation testing and VAS scoring after the first season, the effectiveness of ILIT was significant. (3) The effects of ILIT continued until the second or third season. (4) Neither allergen-specific antibodies nor Treg/Breg cells changed in the peripheral blood.
Conclusions:
ILIT was safe and effective for Japanese cedar pollinosis. The clinical effects remained for 1-2 years.
... Dysfunction of many of the same cells and inflammatory mediators are involved in the pathogenesis of allergy [17][18][19][20][21][22]. However, there have been limited studies investigating how allergy may be related to infertility and those that have been performed have yielded inconsistent results. ...
Purpose
To determine the prevalence of allergy in couples undergoing in vitro fertilization (IVF) and the relationship between having allergy and IVF treatment outcomes.
Design
A retrospective cohort study of female infertility patients aged 20–49 years and their male partners undergoing IVF cycles from August 2010 to December 2016 in an academic fertility program.
Results
Prevalence data was collected for 493 couples (935 cycles). Over half of the female patients (54%) had at least one reported allergy versus the cited US prevalence of 10–30%. Antibiotic (54.7%) and non-antibiotic medication (39.2%) were the most common female allergy subtypes. Fewer male patients reported allergy (21.7%). Data on β-hCG outcomes were calculated for 841 cycles from 458 couples with no significant relationship found except for number of cycles including ICSI and number of embryos transferred per cycle (1.81 for those without allergy vs 2.07 for those with allergy, p = 0.07). Female patients with allergy were marginally statistically more likely to have a negative β-hCG (p = 0.07) and less likely to have a successful cycle (p = 0.06). When allergy subgroups were evaluated, there were no significant differences between groups except for a higher number of embryos transferred in women with environmental/other allergies (p = 0.02).
Conclusion
The prevalence of allergy among patients seeking infertility treatment is high compared with the general population. However, allergy was not found to be associated with IVF cycle outcomes. These findings are likely primarily limited by difficulty in defining specific allergy types within a retrospective study.
... These diseases include rhinitis, asthma, urticaria (hives), eczema, food allergy, insect-bite allergy, anaphylaxis and drug-related allergy (Pawankar et al 2012). In addition, there are several factors that contributes to this endemic problem, which include genetic, environmental and prevalence of microbial infection (Mackay et al 2001). ...
... When the upper airway is exposed to allergens, the allergens interact with the IgE antibodies which leads to the release of a number of cytokines, chemokines and inflammatory mediators by mast cells. This leads to the accumulation of T cells, basophils, mast cells, and eosinophils within the nasal cavity (5)(6)(7). The release of cytokines, specifically, interleukin (IL)-4 and IL-13, are known to hold a key role in the pathogenesis of AR (4,8). ...
Background:
Allergic Rhinitis (AR) is an IgE-mediated inflammatory disorder with high morbidity rates. The eitiology of this disease is understood to occur from a complex interaction between genetic and environmental factors. T helper type 2 cells have been shown to have a crucial role in atopic disease due to their production of the cytokines, intelukin (IL)-13 and IL-4, involved in inflammation. Research has shown single nucleotide polymorphisms (SNP) of the IL-13 and IL-4 genes to be associated increased levels of IgE and with allergic diseases such as, allergic rhinitis, asthma, and atopic dermatitis. Specifically, the rs2243250 SNP of IL-4 and the rs20541 SNP of IL-13 have been shown to be associated with AR.
Methods:
A case-control study was designed to investigate the relationship between the two SNPs rs2243250 and rs20541 with the incidence of AR. The SNPs were examined in patients with AR and healthy controls (86 patients and 86 controls). Blood samples were collected and DNA was extracted to evaluate the SNPs by RFLP-PCR.
Results:
Recessive analysis model of the IL-13 gene (GG vs. AA+AG) revealed that the GG genotype was more common in AR patients (P=0.36) )OR=0.8 [81% CI 0.38-1.6]). For the IL-4 gene (TC vs. TT+CC), the TC genotype was more common in AR patients (P = 0.0022)) OR=0.71 [60% CI 1.41-5.02]). Furthermore, in the IL-4 gene, the 590 T>C polymorphism had a significant association with AR. However, no association was found between AR and the IL-13 rs20541 polymorphism.
Conclusion:
Our findings suggest that the IL-13 polymorphism (rs20541, Exo 4, G>A, Arg130Gln) and IL-4 polymorphism (rs2243250= C-590T, promoter, T>C) are co-associated with AR and sensitivity to aeroallergens. However, this study used a cohort of AR patients and healthy controls from the northeast of Iran. Given the influence of ethnicity and environment on genetics, further investigation is needed to elucidate the role of SNPs in IL-4 and IL-13 in AR among different populations.
... Early studies looked at the 19 effects on perennial/persistent rhinitis and more recent studies 6.7 have looked at the effect on 20 seasonal/intermittent allergic rhinitis. Phototherapy has an immunosuppressive effect and is 21 widely used for the treatment of immune mediated skin diseases. Phototherapy devices are able to inhibit immediate type hypersensitivity reaction in the skin. ...
Previous published work has indicated that treatment of the inside of the nose with certain wavelengths of light can reduce the symptoms of allergic rhinitis. The objective of the study was to compare the efficacy of the phototherapy device on the relief of a range of symptoms provoked by indoor and outdoor allergens. A phototherapy emits visible light (mUV/VIS) and infra red light and was compared to a placebo device which did not emit light on a two groups of allergic rhinitis sufferers. Rhinophototherapy improved nasal symptoms of allergic rhinitis arising from exposure to indoor and outdoor allergens. The difference in the intensity of symptoms scored at the baseline and at the final visit for the group using the photoperiod device was significantly lower. The device could potentially help improve the quality of life for allergy sufferers. Phototherapy may be suitable for sufferers either as a replacement therapy or used alongside traditional medication.
... Early studies looked at the 19 effects on perennial/persistent rhinitis and more recent studies 6.7 have looked at the effect on 20 seasonal/intermittent allergic rhinitis. Phototherapy has an immunosuppressive effect and is 21 widely used for the treatment of immune mediated skin diseases. Phototherapy devices are able to inhibit immediate type hypersensitivity reaction in the skin. ...
Previous published work has indicated that treatment of the inside of the nose with certain wavelengths of light can reduce the symptoms of allergic rhinitis. The objective of the study was to compare the efficacy of the phototherapy device on the relief of a range of symptoms provoked by indoor and outdoor allergens. A phototherapy emits visible light (mUV/VIS) and infrared light, and was compared to a placebo device which did not emit light on two groups of allergic rhinitis sufferers. Rhinophototherapy improved nasal symptoms of allergic rhinitis arising from exposure to indoor and outdoor allergens. The difference in the intensity of symptoms scored at the baseline, and at the final visit for the group using the photoperiod device was significantly lower. The device could potentially help improve the quality of life for allergy sufferers. Phototherapy may be suitable for sufferers either as a replacement therapy or used alongside traditional medication.
... Th1/Th2 immune balance lies at the basis of various immunological diseases, including allergy. It has been widely demonstrated that Th2 immunity is responsible for allergic responses and the subsequent pathogenesis of allergic inflammation (19,20). AD is one such allergic disease, and Th2 cells are markedly increased in the peripheral blood and acute skin lesions of AD patients (1). ...
Background:
It is widely acknowledged that Langerhans cells (LCs) play a primary role in the polarization of T helper type 1 (Th1) or T helper type 2 (Th2) immune responses. Our aim was to find fluoroquinolone ("new quinolone") antibiotics that would inhibit LC-mediated Th2 cell development.
Methods:
Expression of LC surface molecules was investigated using the reverse transcriptase polymerase chain reaction. The effects of fluoroquinolone antibiotics on T-cell immunoglobulin and mucin domain-containing protein (TIM)-4 expression in LCs were examined to predict whether they would inhibit Th2 cell development. Mice were primed via the hind footpad with ovalbumin (OVA) peptide-pulsed LCs that had been treated with a selected fluoroquinolone antibiotic, then 5 days later the cytokine response in popliteal lymph nodes was examined by enzyme-linked immunosorbent assay.
Results:
Norfloxacin was selected as a candidate inhibitor of Th2 cell development. As expected, OVA peptide-pulsed LCs that had been treated with norfloxacin and injected into the hind footpads of mice inhibited Th2 cell development, as represented by down-regulation of interleukin (IL)-4 production, as well as Th1 cell development, as represented by down-regulation of interferon (IFN)- g production. This additional inhibition of Th1 cell development was accompanied by suppression of CD40 expression in LCs. In addition, Staphylococcus aureus strains isolated from skin lesions of patients with atopic dermatitis (AD) were more susceptible to norfloxacin than to gentamicin. Topical treatment with norfloxacin significantly suppressed the increase in the skin severity score in NC/Nga mice with AD-like skin lesions. This suppressive effect was associated with a decrease in the production of IFN-g and IL-4 in auricular lymph node cells.
Conclusions:
The present results show that topical application of norfloxacin inhibits the development of AD-like skin lesions in NC/Nga mice. This suggests that topical application of norfloxacin to AD lesions colonized with S. aureus would act on both superficial S. aureus and epidermal LCs, thus possibly inhibiting the development of Th1 and Th2 cells in vivo, and controlling the severity of AD.
... Most allergic diseases like bronchial asthma, allergic rhinitis and atopic dermatitis are thought to be related with the Th1/Th2 immune imbalance [14][15][16]. As we all know, levels of IFN-γ and IL-4 are usually used to reflect the Th1/Th2 balance in allergy [17][18][19]. ...
Ginsenoside Rh 2 is one of the rare ginsenosides extracted from Panax ginseng C. A. Mey. The anti-allergic activity of ginsenoside Rh 2 has been documented in some literature. In this work, an anti-allergic mechanism of ginsenoside Rh 2 was investigated by focusing on the differentiation of T cells through Langerhans cells (LCs). Langerhans cell-like dendritic cells (LDCs) were generated in vitro and were used as substitute for LCs. In vivo the mRNA expression for IFN-γ and CXCR3 of T cells was increased after being injected with ginsenoside Rh 2 -treated LDCs thereby increasing the concentration of IFN-γ in the culture supernatants of CD3 ⁺ /CD28 ⁺ T lymphocytes. However, in vitro , the expression of mRNA for CD40 and CD80 on ginsenoside Rh 2 -treated LDCs was up-regulated significantly and the endocytic activity of LDCs was down-regulated slightly. These findings indicate that T cells differentiation could be regulated by ginsenoside Rh 2 through LDCs in vivo by altering the antigen presenting capacity, maturation and phagocytosis of LDCs.
... Anti-allergic drugs such as antihistamines and anticholinergics besides topical corticosteroids for specific allergens are available for the management of allergic disorders. But they exhibited adverse side effects like drowsiness, sedation, lethargy, angioedema, immunosuppression etc. in patients and provide only symptomatic relief [15] . ...
... The incidence of food allergy is multifactorial and has been linked to a number of factors including: genetic background, route of exposure, allergen dose, and the molecular properties of the allergen which are all pivotal in determining the clinical presentation of symptoms (4,5). ...
Background: Gamma irradiation is a form of processing with an array of applications in medical sciences such as microbial decontamination, viruses inactivation, cervical carcinoma and breast cancer treatment. One of the ways in which gamma irradiation has the potential to be used is in reducing the allergenicity of food allergens.
Methods: In the present study, pistachios were irradiated with either a 1, 10, or 100 kGy dose of gamma irradiation. The binding rate of mice and human antibodies to the allergens of the pistachio extracts were examined via Western blot analysis.
Results: Our findings show an inverse dose-response relationship between the binding rate of antibodies to the pistachio allergens and the gamma irradiation dose. Despite these promising findings, the results of our sensory evaluation indicate that gamma irradiation causes undesirable changes to the sensory characteristics of pistachios, especially at the dose of 100 kGy.
Conclusions: Gamma irradiation appears to be an effective method in reducing the allergenicity of pistachios. Thus, this form of processing has the potential to prevent adverse allergic reactions to the major pistachio allergens in sensitized subjects. However, further research must be dedicated to examining the dose sufficient in reducing allergencity, while maintaining adequate sensory quality for satisfactory consumption.
Background:
Exposure to disinfection by-products has been associated with several allergic diseases, but its association with allergen-specific immunoglobulin E (IgE) antibodies remains inconclusive.
Methods:
We included 932 U.S. adolescents and 2187 adults from the National Health and Nutrition Examination Survey 2005-2006 who had quantified blood THM concentrations [chloroform (TCM), bromodichloromethane (BDCM), dibromochloromethane (DBCM), and bromoform (TBM)] and 19 allergen-specific IgE antibodies. The odds ratios (ORs) of allergen-specific sensitization per 2.7-fold increment in blood THM concentrations were estimated by multivariable logistic regression models.
Results:
Blood THM concentrations were unrelated to any allergen-specific sensitization in adults. Among adolescents, however, we found positive associations between blood TCM and chlorinated THMs (Cl-THMs: sum of TCM, BDCM, and DBCM) concentrations and the odds of pet sensitization [OR = 1.28 (95 % CI: 1.05, 1.55) and 1.38 (1.15, 1.65), respectively, per each 2.7-fold increment], between blood BDCM concentrations and the odds of mold [OR = 1.47 (1.24, 1.74)], plant [OR = 1.25 (1.09, 1.43)], pet [OR = 1.27 (1.07, 1.52)], and food sensitization [OR = 1.18 (1.03, 1.36)], and between blood brominated THM (Br-THMs: sum of BDCM, DBCM, and TBM) and total THM (TTHMs: sum of 4 THMs) concentrations and the odds of mold [OR = 1.52 (1.30 1.78) and 1.30 (1.03, 1.65), respectively], dust mite [OR = 1.39 (1.06, 1.82) and 1.45 (1.06, 1.98), respectively], and pet sensitization [OR = 1.42 (1.05, 1.92) and 1.54 (1.19, 1.98), respectively].
Conclusion:
Higher blood concentrations of THMs were associated with a greater risk of allergic sensitization among U.S. adolescents but not in adults.
Although the T helper 2 (Th2) subset is a critical player in the humoral immune response to extracellular parasites and suppression of Th1-mediated inflammation, Th2 cells have been implicated in allergic inflammatory diseases such as asthma, allergic rhinitis, and atopic dermatitis. GATA binding protein 3 (GATA3) is a primary transcription factor that mediates Th2 differentiation and secretion of Th2 cytokines, including IL-4, IL-5, and IL-13. Here, a nucleus-deliverable form of GATA3-transcription modulation domain (TMD) (ndG3-TMD) was generated using Hph-1 human protein transduction domain (PTD) to modulate the transcriptional function of endogenous GATA3 without genetic manipulation. ndG3-TMD was shown to be efficiently delivered into the cell nucleus quickly without affecting cell viability or intracellular signaling events for T cell activation. ndG3-TMD exhibited a specific inhibitory function for the endogenous GATA3-mediated transcription, such as Th2 cell differentiation and Th2-type cytokine production. Intranasal administration of ndG3-TMD significantly alleviated airway hyperresponsiveness, infiltration of immune cells, and serum IgE level in an OVA-induced mouse model of asthma. Also, Th2 cytokine secretion by the splenocytes isolated from the ndG3-TMD-treated mice substantially decreased. Our results suggest that ndG3-TMD can be a new therapeutic reagent to suppress Th2-mediated allergic diseases through intranasal delivery.
Cutting-edge technologies such as genome editing and synthetic biology allow us to produce novel foods and functional proteins. However, their toxicity and allergenicity must be accurately evaluated. Allergic reactions are caused by specific amino-acid sequences in proteins (Allergen Specific Patterns, ASPs), of which, many remain undiscovered. In this study, we introduce a data-driven approach and a machine-learning (ML) method to find undiscovered ASPs. The proposed method enables an exhaustive search for amino-acid sub-sequences whose frequencies are statistically significantly higher in allergenic proteins. As a proof-of-concept (PoC), we created a database containing 21,154 proteins of which the presence or absence allergic reactions are already known, and the proposed method was applied to the database. The detected ASPs in the PoC study were consistent with known biological findings, and the allergenicity prediction accuracy using the detected ASPs was higher than extant approaches.
Teaser
We propose a computational method for finding statistically significant allergen-specific amino-acid sequences in proteins.
Allergen-specific inflammation is a particular manifestation of inflammation, a universal form of reactivity aimed at eliminating damage and restoring homeostasis. Modern data are presented that confirm the idea that the natural resolution of inflammation is an active process performed by coordinated cellular reactions. This process is induced and carried out by the action of anti-inflammatory mediators of various chemical nature and specialized lipid mediators. The mechanism for restriction and resolving inflammation includes inactivation of pro-inflammatory mediators, limitation of further recruitment and activation of inflammatory cells, apoptosis of these cells, switching of macrophages from M1 to M2 type, enhancement of efferocytosis, promoting the return of cells that have not undergone apoptosis to lymphatic and blood vessels, and initiation of tissue repair. Insufficiency or loss of anti-inflammatory and proresolving functions leads to prolongation of the inflammatory reaction, chronic inflammation, tissue remodeling and allergen-nonspecific tissue hyperreactivity. Restoration of insufficient or lost resolving function is a strategically justified task of creating new therapeutic approaches.
CD4 ⁺ T helper (T H ) cells and regulatory T (T reg ) cells that respond to common allergens play an important role in driving and dampening airway inflammation in patients with asthma. Until recently, direct, unbiased molecular analysis of allergen-reactive T H and T reg cells has not been possible. To better understand the diversity of these T cell subsets in allergy and asthma, we analyzed the single-cell transcriptome of ~50,000 house dust mite (HDM) allergen–reactive T H cells and T reg cells from asthmatics with HDM allergy and from three control groups: asthmatics without HDM allergy and nonasthmatics with and without HDM allergy. Our analyses show that HDM allergen–reactive T H and T reg cells are highly heterogeneous and certain subsets are quantitatively and qualitatively different in individuals with HDM-reactive asthma. The number of interleukin-9 (IL-9)–expressing HDM-reactive T H cells is greater in asthmatics with HDM allergy compared with nonasthmatics with HDM allergy, and this IL-9–expressing T H subset displays enhanced pathogenic properties. More HDM-reactive T H and T reg cells expressing the interferon response signature (T H IFNR and T reg IFNR) are present in asthmatics without HDM allergy compared with those with HDM allergy. In cells from these subsets (T H IFNR and T reg IFNR), expression of TNFSF10 was enriched; its product, tumor necrosis factor–related apoptosis-inducing ligand, dampens activation of T H cells. These findings suggest that the T H IFNR and T reg IFNR subsets may dampen allergic responses, which may help explain why only some people develop T H 2 responses to nearly ubiquitous allergens.
Some cytokines ,IgE and genetic study of
Staphylococcus aureus superantigens in patients of Allergic rhinitis
Die atopische Dermatitis gehört zu den häufigsten chronisch-entzündlichen Hauterkrankungen. Sie steht im Verdacht, andere Erkrankungen zu begünstigen — darunter kardiovaskuläre Ereignisse, chronisch-entzündliche Darmerkrankungen oder Infektionskrankheiten. Ein Zusammenhang ist aber nicht in allen Fällen eindeutig belegt.
Die atopische Dermatitis (AD) ist eine der häufigsten chronisch-entzündlichen Dermatosen. Gekennzeichnet ist sie durch juckende, ekzematöse Hauteffloreszenzen. Aufgrund nachweisbarer Zeichen einer systemischen Entzündung sowie neuer systemischer Therapieoptionen rückten in den letzten Jahren zunehmend Untersuchungen von internistischen Komorbiditäten bei moderater bis schwerer AD in den Fokus der Forschung. Dabei wurde zum einen an prospektiven Kohortenstudien das lange bekannte erhöhte Risiko für andere atopische Erkrankungen wie das allergische Asthma bronchiale bestätigt. Zum anderen wurde eine Assoziation mit anderen dermatologischen Erkrankungen mit autoimmunologischer Pathogenese wie der Alopecia areata oder der Vitiligo gezeigt. Darüber hinaus wurden in den letzten Jahren auch Studien publiziert, die ein erhöhtes Risiko für internistische Autoimmunerkrankungen wie chronisch-entzündliche Darmerkrankungen oder rheumatoide Arthritis zeigten. Daten zur AD, die die Hautkrankheit als kardiovaskulären Risikofaktor postulieren, müssen differenziert betrachtet werden: Lediglich in den USA zeigten Querschnittsstudien und Auswertungen von Krankenkassendaten einen Zusammenhang zwischen AD und kardiovaskulären Komorbiditäten. Dies ließ sich in deutschen, dänischen und kanadischen Studien mit großen Stichprobenzahlen bislang nicht bestätigen. Inwieweit unterschiedliche Coping-Strategien in den verschiedenen Ländern die Manifestation von kardiovaskulären Erkrankungen bei AD beeinflussen, ist zu diskutieren. Bezüglich internistisch-mikrobiologischer Komorbiditäten lässt sich bei AD insbesondere eine Suszeptibilität gegenüber viralen Infektionen aufzeigen.
Die Zulassung von Dupilumab als erstes Biologikum markiert den Anfang eines neuen Zeitalters in der Behandlung der mittelschweren bis schweren atopischen Dermatitis. Dieser Artikel liefert einen Einblick in neue Erkenntnisse zur Pathogenese mit Implikationen für die Therapie, Daten zur Therapieversorgung in Deutschland sowie aktuelle Entwicklungen in der Systemtherapie.
Most urticarias are induced by vasoactive mediators such as histamine released from mast cells. Although mast cells are activated by allergens through cross-linking of cell-surface--bound IgE, this mechanism does not appear to explain most cases of chronic urticaria, which, when allergic, infectious, drug-induced, or physical causes cannot be identified, are classified as idiopathic.
We recruited 26 patients with chronic idiopathic urticaria, in whom intradermal injection of autologous serum caused a wheal-and-flare response. Serum from four patients that induced marked histamine release from basophils from a donor with very low serum IgE levels was studied with respect to the IgE dependence of the histamine release, the activity of the IgG fractions, and the neutralizing effect of a recombinant preparation of the soluble extracellular domain of the alpha subunit of the high-affinity IgE receptor (sFc epsilon RI alpha).
The histamine-releasing activity of the serum was abolished by passive sensitization of basophils with myeloma IgE, enhanced after dissociation of IgE by treatment with lactic acid, and induced by IgG fractions from the serum of all four patients. Preincubation of the serum and isolated IgG with sFc epsilon RI alpha resulted in almost complete neutralization.
Histamine-releasing IgG autoantibodies against the alpha subunit of the high-affinity IgE receptor are present in the circulation of some patients with chronic urticaria. Autoantibody-induced cross-linking of IgE receptors may be an important mechanism in the pathogenesis of chronic urticaria and other diseases mediated by mast cells.
We have studied the influence of grass pollen immunotherapy on cellular infiltration and cytokine mRNA expression during allergen-induced late-phase cutaneous responses. In a double-blind, placebo-controlled trial of immunotherapy in 40 adult hay fever sufferers, clinical improvement was accompanied by a decrease in the size of the late-phase skin response. When the immunotherapy-treated group was compared with the placebo group, analysis of skin biopsies obtained 24 h after intradermal allergen revealed a significant reduction in the number of infiltrating CD3+ (P = 0.04) and CD4+ (P = 0.009) cells and a trend for a decrease in EG2+ eosinophils (P = 0.08). Treatment did not influence allergen-induced recruitment of CD8+ cells, neutrophils, or macrophages. Unexpected increases in expression of CD25 (P = 0.006) and HLA-DR (P = 0.007) were observed in the actively treated group. In situ hybridization using a panel of riboprobes demonstrated "TH2-type" (IL-4, IL-5) cytokine mRNA responses in both groups of patients. In contrast, significant hybridization for IL-2 (8/16 patients, P = 0.02) and for interferon-gamma (6/16 patients, P = 0.04) was observed only in the actively treated group. These findings indicate that immunotherapy is associated with suppression of allergen-induced CD4+ T lymphocyte infiltration, but among the cells that are recruited, there is upregulation of CD25 and HLA-DR. At least in this model, immunotherapy does not appear to affect expression of TH2-pattern cytokines in response to allergen exposure, but expression of mRNA for Th1-type cytokines was enhanced in half of the patients. The results support the view that immunotherapy may possibly be working through induction of T cell tolerance.
The induction of allergen-specific anergy in peripheral T cells represents a key step in specific immunotherapy (SIT). Here we demonstrate that the anergic state results from increased IL-10 production. In bee venom (BV)-SIT the specific proliferative and cytokine responses against the main allergen, the phospholipase A2 (PLA), and T cell epitope-containing PLA peptides were significantly suppressed after 7 d of treatment. Simultaneously, the production of IL-10 increased during BV-SIT. After 28 d of BV-SIT the anergic state was established. Intracytoplasmic cytokine staining of PBMC combined with surface marker detection revealed that IL-10 was produced initially by activated CD4(+)CD25(+), allergen-specific T cells, and followed by B cells and monocytes. Neutralization of IL-10 in PBMC fully reconstituted the specific proliferative and cytokine responses. A similar state of IL-10-associated T cell anergy, as induced in BV-SIT, was found in hyperimmune individuals who recently had received multiple bee stings. The addition of IL-10 to soluble CD40 ligand IL-4-stimulated PBMC or purified B cells inhibited the PLA-specific and total IgE and enhanced the IgG4 formation. Accordingly, increased IL-10 production by SIT causes specific anergy in peripheral T cells, and regulates specific IgE and IgG4 production toward normal IgG4-related immunity.
Pollen immunotherapy is effective in selected patients with IgE-mediated seasonal allergic rhinitis, although it is questionable whether there is long-term benefit after the discontinuation of treatment.
We conducted a randomized, double-blind, placebo-controlled trial of the discontinuation of immunotherapy for grass-pollen allergy in patients in whom three to four years of this treatment had previously been shown to be effective. During the three years of this trial, primary outcome measures were scores for seasonal symptoms and the use of rescue medication. Objective measures included the immediate conjunctival response and the immediate and late skin responses to allergen challenge. Cutaneous-biopsy specimens obtained 24 hours after intradermal allergen challenge were examined for T-cell infiltration and the presence of cytokine-producing T helper cells (TH2 cells) (as evidenced by the presence of interleukin-4 messenger RNA). A matched group of patients with hay fever who had not received immunotherapy was followed as a control for the natural course of the disease.
Scores for seasonal symptoms and the use of rescue antiallergic medication, which included short courses of prednisolone, remained low after the discontinuation of immunotherapy, and there was no significant difference between patients who continued immunotherapy and those who discontinued it. Symptom scores in both treatment groups (median areas under the curve in 1995, 921 for continuation of immunotherapy and 504 for discontinuation of immunotherapy; P=0.60) were markedly lower than those in the group that had not received immunotherapy (median value in 1995, 2863). Although there was a tendency for immediate sensitivity to allergen to return late after discontinuation, there was a sustained reduction in the late skin response and associated CD3+ T-cell infiltration and interleukin-4 messenger RNA expression.
Immunotherapy for grass-pollen allergy for three to four years induces prolonged clinical remission accompanied by a persistent alteration in immunologic reactivity.
We dissected the T cell activation potency and the immunoglobulin (Ig) E-binding properties (allergenicity) of nine isoforms of Bet v 1 (Bet v 1a-Bet v 1l), the major birch pollen allergen. Immunoblot experiments showed that Bet v 1 isoforms differ in their ability to bind IgE from birch pollen-allergic patients. All patients tested displayed similar IgE-binding patterns toward each particular isoform. Based on these experiments, we grouped Bet v 1 isoforms in three classes: molecules with high IgE-binding activity (isoforms a, e, and j), intermediate IgE-binding (isoforms b, c, and f), and low/no IgE-binding activity (isoforms d, g, and 1). Bet v 1a, a recombinant isoform selected from a cDNA expression library using IgE immunoscreening exhibited the highest IgE-binding activity. Isoforms a, b, d, e, and 1 were chosen as representatives from the three classes for experimentation. The potency of each isoallergen to activate T lymphocytes from birch pollen-allergic patients was assayed using peripheral blood mononuclear cells, allergen-specific T cell lines, and peptide-mapped allergen-specific T cell clones. Among the patients, some displayed a broad range of T cell-recognition patterns for Bet v 1 isoforms whereas others seemed to be restricted to particular isoforms. In spite of this variability, the highest scores for T cell proliferative responses were observed with isoform d (low IgE binder), followed by b, 1, e, and a. In vivo (skin prick) tests showed that the potency of isoforms d and 1 to induce typical urticarial type 1 reactions in Bet v 1-allergic individuals was significantly lower than for isoforms a, b, and e. Taken together, our results indicate that hypoallergenic Bet v 1 isoforms are potent activators of allergen-specific T lymphocytes, and Bet v 1 isoforms with high in vitro IgE-binding activity and in vivo allergenicity can display low T cell antigenicity. Based on these findings, we propose a novel approach for immunotherapy of type I allergies: a treatment with high doses of hypoallergenic isoforms or recombinant variants of atopic allergens. We proceed on the assumption that this measure would modulate the quality of the T helper cell response to allergens in vivo. The therapy form would additionally implicate a reduced risk of anaphylactic side effects.
Immune responses mediated by IgE are important in the pathogenesis of allergic asthma. A recombinant humanized monoclonal antibody (rhuMAb-E25) forms complexes with free IgE and blocks its interaction with mast cells and basophils. We studied the efficacy of rhuMab-E25 as a treatment for moderate-to-severe allergic asthma.
After a 4-week run-in period, we randomly assigned 317 subjects (age range, 11 to 50 years) who required inhaled or oral corticosteroids (or both) to receive either placebo or one of two regimens of rhuMAB-E25: high-dose rhuMAb-E25 (5.8 microg per kilogram of body weight per nanogram of IgE per milliliter or low-dose rhuMAb-E25 (2.5 microg per kilogram per nanogram of IgE per milliliter) intravenously on days 0 (half a dose), 4 (half a dose), and 7 (full dose) and then once every 2 weeks thereafter for 20 weeks. For the first 12 weeks of the study, the subjects continued the regimen of corticosteroids they had received before enrollment. During the following eight weeks, the doses of corticosteroids were tapered in an effort to discontinue this therapy. The primary outcome measure was an improvement in the asthma symptom score at 12 weeks, according to a 7-point scale, in which a score of 1 indicated no symptoms and a score of 7 the most severe symptoms.
A total of 106 subjects were assigned to receive a high dose of rhuMAb-E25, 106 were assigned to receive a low dose, and 105 were assigned to receive placebo. At base line, the mean asthma symptom score was 4.0. After 12 weeks of therapy, the mean (+/-SE) scores were 2.8+/-0.1 in the high-dose group (P=0.008) and 2.8+/-0.1 in the low-dose group (P=0.005), as compared with 3.8+/-0.1 in the placebo group. At 20 weeks, the mean scores were 2.7+/-0.1 in both the high-dose group (P=0.048) and the low-dose group (P=0.14), as compared with 2.9+/-0.1 in the placebo group. More subjects in the two rhuMAb-E25 groups were able to decrease or discontinue their use of corticosteroids than in the placebo group, but only some of the differences were significant. After 20 weeks, serum free IgE concentrations decreased by a mean of more than 95 percent in both rhuMAb-E25 groups. The therapy was well tolerated. After 20 weeks, none of the subjects had antibodies against rhuMAb-E25.
A recombinant humanized monoclonal antibody directed against IgE has potential as a treatment for subjects with moderate or severe allergic asthma.
Histamine-releasing autoantibodies have been identified in chronic idiopathic urticaria. 8 patients with severe disease and histamine-releasing activity in their sera underwent plasmapheresis. Symptoms were abolished for 2 months in 1 patient and for 3 weeks in another, 2 showed almost complete resolution of symptoms, 2 had temporary relief, and the other 2 showed little change. Further investigation in 4 of the patients showed significantly reduced skin-test responses to fresh post-exchange autologous sera after plasmapheresis compared with stored pre-exchange sera, but the response to intradermal histamine remained unchanged. Blood cellular histamine increased as in-vitro serum histamine-releasing activity fell after plasmapheresis. These results favour a pathogenetic role for histamine-releasing autoantibodies in patients with chronic urticaria.
Previous studies showed that pollens from trees of the order Fagales (e.g. birch, alder, hazel and hornbeam) all contain one major allergen. These proteins are cross-reactive between these tree species, and approximately 95% of tree-pollen-allergic patients display IgE binding to these allergens. Using the reported N-terminal amino acid sequence of the hazel pollen allergen Cor a I, it was possible to amplify Cor-a-I cDNA by use of the polymerase chain reaction. Four clones with cDNA inserts were isolated. All four clones contained an open reading frame of 477 nucleotides (159 amino acids) but differed in length of their 3'-non-coding regions. Within the overlapping regions, the nucleotide sequence of the 3'-non-coding regions of the four clones were nearly identical. The open reading frames coded for different isoforms of the major hazel pollen allergen, Cor a I. The clones were designated Cor a I/5, 6, 11 and 16, respectively. Comparison of the deduced amino acid sequences of these Cor a I isoforms revealed identities of 96-99%. The sequence identities between the Cor a I isoforms and Bet v I, the major birch pollen allergen, were 71-73% (80.5-83% similarity). Comparing amino acid sequences of Cor a I isoforms with the published sequences of Aln g I, the major allergen from alder, and Car b I and isoforms, the major allergen from hornbeam, 75.5-76.7% identity (83.6-85% similarity) and 83.6-89.9% sequence identity (89.3-95% similarity), respectively, was found. The four Cor a I cDNAs were subcloned into plasmid pKK223-3 and expressed in Escherichia coli as non-fusion proteins; their capacity to bind serum IgE from tree-pollen-allergic patients was investigated. The four cloned isoforms showed an apparent molecular mass of 17 kDa in SDS/PAGE, identical to the natural, pollen-derived Cor a I. IgE antibodies from tree-pollen-allergic patients reacted with all four recombinant isoforms. However, we noted marked differences in the IgE-binding patterns of the distinct isoforms. Furthermore, Cor a I/11 was the only isoform recognized by the anti-(Bet v I) mAb, BIP 1. Our results demonstrate that Cor a I isoforms display different antigenic and allergenic properties, very likely due to few but significant changes in their amino acid sequences. These findings have implications for the development of reagents for diagnosis and immunotherapy of type I allergies.
The role of housedust-mite (HDM) allergen (Der p1) in the pathogenesis of atopic dermatitis is controversial. We tested the hypothesis that atopic dermatitis improves if amounts of HDM allergen in the home are reduced.
Active treatment comprised Goretex bedcovers (placebo, cotton covers), benzyltannate spray (placebo, water), and a high-filtration vacuum cleaner (placebo, a conventional domestic vacuum cleaner). Dust was sampled monthly from the mattress covers and bedroom and living-room carpets. 48 patients (24 adults [mean age 30] and 24 children [mean age 10]) completed the 6-month study. 28 were in the active treatment group and 20 in the placebo group.
The weight of dust collected from Goretex-covered mattresses had fallen by 98% at 1 month (from 386 to 9 mg/m2) with no change thereafter. Placebo covers caused a smaller reduction in dust load (361 to 269 mg/m2); the difference between active and placebo covers at 6 months was highly significant (p = 0.002). Both active and placebo treatments caused significant reductions in Der p1 concentrations in bedroom and living-room carpets and the differences between the treatments were not significant. The severity of eczema decreased in both groups, but the active group showed significantly greater improvements in severity score (difference between mean final scores 4.3 units, p = 0.006) and area affected (difference between mean final areas 10%, p = 0.006) in analysis of covariance with initial mattress dust weights and bedroom carpet Der p1 load as covariates. Reported analysis with final values for the covariates showed that most of the treatment effect was due to the reduction in mattress dust and carpet Der p1.
The activity of atopic dermatitis can be greatly reduced by effective HDM avoidance. Methods to identify individuals who will benefit most from such measures are needed.
A variety of vaccine delivery systems including peptides with various adjuvants, recombinant particles, live recombinant viruses and bacteria and plasmid DNA were tested for their ability to induce CD8+ cytotoxic T lymphocytes (CTL) against a well-defined epitope (amino acids 252-260) from the circumsporozoite (CS) protein of Plasmodium berghei. We compared routes of immunization that would be applicable for the administration of a malaria vaccine in humans. The majority of these vaccines did not induce high CTL responses in the spleens of immunized mice. However, both a yeast-derived Ty virus-like particle expressing the optimal nine-amino acid epitope SYIPSAEKI from the CS protein (CSP-VLP) and a lipid-tailed peptide of this same sequence induced high levels of the major histocompatibility complex (MHC) class I-restricted CTL with one and three subcutaneous immunizations, respectively. Moreover, these CTL were able to recognize naturally processed antigen expressed by a recombinant vaccinia virus. The levels of CTL induced by CSP-VLP could be augmented by co-immunization with certain cytokines. Target cells pulsed with CSP-VLP were recognized and lysed, showing that the particles were effectively processed and presented through MHC class I presentation pathway. The levels of CTL induced using CSP-VLP and lipopeptides are comparable to those observed after immunization with multiple doses of irradiated sporozoites.
Chemokines bind and signal through G-protein coupled seven transmembrane receptors. Various chemokine receptors are expressed on leukocytes, and these may impart selective homing of leukocyte subsets to sites of inflammation. Human eosinophils express the eotaxin receptor, CCR3, but respond to a variety of CC chemokines apart from eotaxin, including RANTES, monocyte chemotactic protein (MCP)-2, MCP-3, and MCP-4. Here we describe a mAb, 7B11, that is selective for CCR3 and has the properties of a true receptor antagonist. 7B11 blocked binding of various radiolabeled chemokines to either CCR3 transfectants, or eosinophils. Pretreatment of eosinophils with this mAb blocked chemotaxis and calcium flux induced by all CCR3 ligands. In all individuals examined, including allergic and eosinophilic donors, > 95% of the response of eosinophils to eotaxin, RANTES, MCP-2, MCP-3, and MCP-4 was shown to be mediated through CCR3. The IL-8 receptors, particularly CXCR2, were induced on IL-5 primed eosinophils, however these eosinophils responded to CC chemokines in the same manner as unprimed eosinophils. These results demonstrate the importance of CCR3 for eosinophil responses, and the feasibility of completely antagonizing this receptor.
A major peanut allergen, Ara h 2, is recognized by serum IgE from > 90% of patients with peanut hypersensitivity. Biochemical characterization of this allergen indicates that it is a glycoprotein of approximately 17.5 kDa. Using N-terminal amino acid sequence data from purified Ara h 2, oligonucleotide primers were synthesized and used to identify a clone (741 bp) from a peanut cDNA library. This clone was capable of encoding a 17.5-kDa protein with homology to the conglutin family of seed storage proteins. The major linear immunoglobulin E (IgE)-binding epitopes of this allergen were mapped using overlapping peptides synthesized on an activated cellulose membrane and pooled serum IgE from 15 peanut-sensitive patients. Ten IgE-binding epitopes were identified, distributed throughout the length of the Ara h 2 protein. Sixty-three percent of the amino acids represented in the epitopes were either polar uncharged or apolar residues. In an effort to determine which, if any, of the 10 epitopes were recognized by the majority of patients with peanut hypersensitivity, each set of 10 peptides was probed individually with serum IgE from 10 different patients. All of the patient sera tested recognized multiple epitopes. Three epitopes (aa27-36, aa57-66, and aa65-74) were recognized by all patients tested. In addition, these three peptides bound more IgE than all the other epitopes combined, indicating that they are the immunodominant epitopes of the Ara h 2 protein. Mutational analysis of the Ara h 2 epitopes indicate that single amino acid changes result in loss of IgE binding. Two epitopes in region aa57-74 contained the amino acid sequence DPYSP that appears to be necessary for IgE binding. These results may allow for the design of improved diagnostic and therapeutic approaches to peanut hypersensitivity.
Despite the popularity of using plasmid DNA for vaccination, it is only recently that the basic mechanisms that drive the immune response to the encoded antigen have begun to unfold. Here, Helen Tighe and colleagues outline the characteristics of the immune response induced by gene vaccination and describe the multifaceted properties of DNA in initiating and determining the process.
Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by intensely pruritic subacute and chronic eczematous plaques, the pathogenesis of which appears to involve a complex interplay of genetic, pharmacological, environmental and psychological factors. Here, Markus Grewe and colleagues propose that the development of skin lesions in AD patients results from sequential activation of T helper 2 (Th2)- and Th1-type cells.
Specific allergen injection immunotherapy is highly effective in selected patients with IgE-mediated disease, including respiratory allergy and venom anaphylaxis. Research in this area provides insight into the immunologic basis of allergic disease and may assist in the development of more highly targeted treatment. Immunotherapy reduces immediate allergen-induced symptoms and concentrations of inflammatory mediators, including histamine and prostaglandin D2, in ragweed-sensitive patients. Similarly, nasal epithelial mast cell numbers are decreased. A characteristic feature of immunotherapy is its ability to inhibit late-phase responses. In the nose it is accompanied by a decrease in eosinophil numbers in lavage during late responses. Characteristic changes in serum immunoglobulins are found, with an initial increase in IgE followed by a blunting of seasonal increases in IgE in pollen-sensitive patients and a gradual decline in allergen-specific IgE levels over several years. This is accompanied by an increase in allergen-specific IgG (blocking antibodies), although neither appear to correlate closely with the clinical response to immunotherapy. One way in which immunotherapy may act is by modifying the T-lymphocyte response to subsequent natural allergen exposure. Studies in peripheral blood and within the target organ have demonstrated a shift in the balance of T-cell subsets away from TH2-type (producing particularly IL-4 and IL-5) in favor of a TH1-type T-lymphocyte response (with the preferential production of IFN-gamma). Studies of the nasal mucosa before and after immunotherapy have demonstrated suppression of the late nasal response and increases in the numbers of cells expressing mRNA for IFN-gamma. It is not clear whether this immune deviation is due to anergy of TH2/TH0 cells or increases in TH0/TH1 T-lymphocyte responses. An alternative may be amplification of suppressor CD8+ T cells, which may have a downregulatory effect. Novel approaches currently being explored include the use of T-cell reactive peptides, which might circumvent the risk of anaphylaxis, and the use of adjuvants such as IL-12 or mycobacterial vaccines to potentiate the effects of allergen in inducing immune deviation.
Second-generation histamine H1 receptor antagonists (antihistamines) have been developed to reduce or eliminate the sedation and anticholinergic adverse effects that occur with older H1 receptor antagonists. This article evaluates second-generation antihistamines, including acrivastine, astemizole, azelastine, cetirizine, ebastine, fexofenadine, ketotifen, loratadine, mizolastine and terfenadine, for significant features that affect choice.
In addition to their primary mechanism of antagonising histamine at the H1 receptor, these agents may act on other mediators of the allergic reaction. However, the clinical significance of activity beyond that mediated by histamine H1 receptor antagonism has yet to be demonstrated.
Most of the agents reviewed are metabolised by the liver to active metabolites that play a significant role in their effect. Conditions that result in accumulation of astemizole, ebastine and terfenadine may prolong the QT interval and result in torsade de pointes. The remaining agents reviewed do not appear to have this risk. For allergic rhinitis, all agents are effective and the choice should be based on other factors. For urticaria, cetirizine and mizolastine demonstrate superior suppression of wheal and flare at the dosages recommended by the manufacturer.
For atopic dermatitis, as adjunctive therapy to reduce pruritus, cetirizine, ketotifen and loratadine demonstrate efficacy. Although current evidence does not suggest a primary role for these agents in the management of asthma, it does support their use for asthmatic patients when there is coexisting allergic rhinitis, dermatitis or urticaria.
Previous studies defining the clinical features of patients with chronic idiopathic urticaria (CIU) were performed before the identification of functional autoantibodies against FcepsilonRI and/or IgE, now known to be present in approximately 30% of patients with CIU.
Our purpose was to determine whether there are differences between patients with and those without autoantibodies in the clinical features or severity of CIU.
The clinical features of 107 patients with CIU were evaluated prospectively. Patients were identified as having functional autoantibodies on the basis of the serum-evoked histamine release in vitro from the basophils of 2 healthy donors.
Patients with autoantibodies (31%) had more wheals (P = .005), a wider distribution of wheals (P = .009), higher itch scores for the most severe episodes of itching (P = .002), more systemic symptoms (P = .03), and lower serum IgE levels (P < .0005) than patients without autoantibodies.
The presence of autoantibodies indicates a subset of patients with more severe CIU.
Intrinsic asthma shows no clinical or serological evidence of IgE-mediated allergy to common environmental agents. Similar to extrinsic asthma, bronchial biopsies from such patients show enhanced expression of Th2-type cytokines, CC chemokines and Iϵ/Cϵ compared with controls. These findings suggest there might be local IgE production directed against unknown antigens, possibly of viral origin or even autoantigens, in this important clinically distinct variant of the disease.