[Show abstract][Hide abstract] ABSTRACT: IgE antibodies specific for the major birch pollen allergen frequently cross-react with Bet v 1 homologous food proteins, for example Cor a 1 in hazelnut and Mal d 1 in apple. Specific immunotherapy with birch pollen (BP-SIT) induces IgG4 antibodies that inhibit IgE binding to Bet v 1. However, information on cross-reactivity of BP-SIT-induced Bet v 1-specific IgG4 antibodies with food allergens is limited. In this study, we investigated the kinetics of production, cross-reactivity, and IgE-blocking activity of Bet v 1-specific IgG4 antibodies emerging during conventional BP-SIT and whether IgG4-epitopes overlapped with IgE epitopes.
IgE and IgG4 levels specific for Bet v 1, Mal d 1, and Cor a 1 were determined in 42 birch pollen-allergic patients before and during BP-SIT. Inhibition of IgE binding was studied by IgE-facilitated antigen-binding assays and basophil activation tests. Furthermore, inhibition of IgE-mediated activation of food allergen-reactive Bet v 1-specific T-cell lines was assessed. Competitive immunoscreening of phage-displayed peptides was applied to select mimotopes recognized by IgE and IgG4 antibodies, respectively. The resulting mimotopes were mapped on the surface of the 3D structure of the allergens using a computer-based algorithm.
BP-SIT significantly increased Bet v 1- and food allergen-reactive IgG4 antibodies. In parallel, allergen-specific IgE levels decreased significantly. Sera containing food allergen-reactive IgG4 antibodies inhibited IgE binding, basophil activation, and IgE-mediated food allergen-induced T-cell proliferation. Predicted IgE and IgG4 epitopes on all allergens showed high overlap.
Our results indicate that BP-SIT may induce Bet v 1-specific IgG4 antibodies that cross-react with related food allergens and inhibit IgE binding by epitope competition.
[Show abstract][Hide abstract] ABSTRACT: Background: A 29-year-old female presented with a first-time anaphylactic reaction.
History revealed the intake of “Schwarzbeernocken”, a Tyrolean speciality containing
blueberries, 1 hour prior to the onset of symptoms. We aimed to identify the culprit
allergen. Methods: Serum from a blueberry allergic donor was studied for IgE reactivity
to blueberry, mugwort (Artemisia vulgaris) and birch (Betula verrucosa) pollen extract
in IgE immunoblot experiments. IgE inhibition experiments and N-terminal sequencing
were performed to further identify the putative blueberry allergen. In addition, blueberry
extract was evaluated for cross-reactive allergens with sera from a Bet v 1- and a monosensitized
mugwort pollen-allergic patient.
Results: Blueberries contain a 9 kDa allergen which cross-reacts with Pru p 3, the nonspecific lipid transfer protein from peach, and shows sequence homology with cabbage lipid transfer protein. No allergen homologous to Bet v 1 could be identified in blueberries.
Conclusion: Blueberry lipid transfer protein represents a relevant food allergen which can cause severe anaphylactic reactions. However, blueberries apparently do not contain any Bet v 1-homologue. This protein family is found in many other foods and known as the most common cause of oral allergy syndrome in the Northern hemisphere.
[Show abstract][Hide abstract] ABSTRACT: Treatment failure during venom immunotherapy (VIT) may be associated with a variety of risk factors.
Our aim was to evaluate the association of baseline serum tryptase concentration (BTC) and of other parameters with the frequency of VIT failure during the maintenance phase.
In this observational prospective multicenter study, we followed 357 patients with established honey bee or vespid venom allergy after the maintenance dose of VIT had been reached. In all patients, VIT effectiveness was either verified by sting challenge (n = 154) or patient self-reporting of the outcome of a field sting (n = 203). Data were collected on BTC, age, gender, preventive use of anti-allergic drugs (oral antihistamines and/or corticosteroids) right after a field sting, venom dose, antihypertensive medication, type of venom, side effects during VIT, severity of index sting reaction preceding VIT, and duration of VIT. Relative rates were calculated with generalized additive models.
22 patients (6.2%) developed generalized symptoms during sting challenge or after a field sting. A strong association between the frequency of VIT failure and BTC could be excluded. Due to wide confidence bands, however, weaker effects (odds ratios <3) of BTC were still possible, and were also suggested by a selective analysis of patients who had a sting challenge. The most important factor associated with VIT failure was a honey bee venom allergy. Preventive use of anti-allergic drugs may be associated with a higher protection rate.
It is unlikely that an elevated BTC has a strong negative effect on the rate of treatment failures. The magnitude of the latter, however, may depend on the method of effectiveness assessment. Failure rate is higher in patients suffering from bee venom allergy.
PLoS ONE 05/2013; 8(5):e63233. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Vorstände der Arbeitsgruppe Allergologie der ÖGDV Leitlinien-Stufe: S-1, informelle Konsensbildung von mit der Thematik vertrauten Experten (Fachärzten für Dermatologie und Venerologie) Verfahren zur Konsensbildung: Komissionssitzungen der Fachgruppe Allergologie der Österreichischen Gesellschaft für Dermatologie und Venerologie (ÖGDV) Expertengruppe/Mitarbeit (alphabetisch): Beirat der Arbeitsgruppe Allergologie der ÖGDV: Prim. Prof. Dr. Werner Aberer (Univ.-Klinik für Dermatologie und Venerologie, 8036 Graz email@example.com), Dr. Johann Derhaschnig (FA für Dermatologie, 9400 Wolfsberg, firstname.lastname@example.org), OA Dr. Daevi Ferch-Haselbach (LKH Klagenfurt, Dermatologi-sche Abteilung, 9026 Klagenfurt, email@example.com), OA Dr. Thomas Hawranek, Paracelsus Medizinische Privatuniversität Salzburg, Univ.-Klinik für Dermatologie, 5020 Salzburg, firstname.lastname@example.org), Doz. Dr. Wolfgang Hemmer (Floridsdorfer Allergie-zentrum, 1210 Wien, email@example.com), Prof. Dr. Reinhart Jarisch (Floridsdorfer Allergiezentrum, 1210 Wien, firstname.lastname@example.org), OÄ Dr. Nicole Kemmler (LKH Feldkirch, Abt. Für Dermatologie, 6897 Feldkirch, Nicole.Kemmler@lkhf.at), Dr. Adelheid Kienzl (FÄ für Dermatologie, 3100 St. Pölten, email@example.com), OÄ Prof. Dr. Tamar Kinaciyan (Univ.-Klinik für Dermatologie, Abt. für Immunder-matologie und infektiöse Hautkrankheiten, 1090 Wien, Tamar.Kinaciyan@meduniwien.ac.at), Prim. Doz. Dr. Georg Klein (Dermatologische Abt. KH der Elisabethinen, 4020 Linz, firstname.lastname@example.org), Doz. Dr. Heinz Kofl er (Allergieambula-torium, 6060 Hall in Tirol, heinz.kofl er@kofl er-haut.at), OA Prof. Dr. Birger Kränke (Univ.-Klinik für Dermatologie und Venerologie, 8036 Graz, email@example.com), Dr. Udo Längle (FA für Dermatologie, 6850 Dornbirn, firstname.lastname@example.org), Prim. Dr. Wolf Pachinger (LKH Klagenfurt, Dermatologische Abteilung, 9026 Klagenfurt, email@example.com), OA Dr. Detlev Pirkhammer (Dermatologische Abteilung der Krankenanstalt Rudolfstiftung, 1030 Wien, firstname.lastname@example.org), Prof. Dr. Norbert Reider (Univ.-Klinik für Dermatologie und Venerologie, 6020 Innsbruck, email@example.com), OA Doz. Dr. Paul Sator (Dermatologie KH Hietzing, 1130 Wien, firstname.lastname@example.org), Prim. Prof. Dr. Georg Stingl (Univ.-Klinik für Dermatologie, Abt. für Immundermatologie und infektiöse Hautkrankheiten, 1090 Wien, email@example.com), OA Dr. Alexander Trost (Abteilung für Dermatologie, Wilhelminenspital, 1160 Wien, firstname.lastname@example.org), em. OA Dr. Manfred Wohofsky (FA für Dermatologie, 9020 Klagenfurt, wohofsky.manfred@aon.
Wiener klinische Wochenschrift 10/2011; · 0.79 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Nowadays, clinical and evidence based guidelines are considered one of the major efforts to improve patient care in medical practices as well as hospital settings. In the literature, clinical guidelines have been defined as "systematically developed statements to assist practitioner and patient decisions about appropriate healthcare for specific clinical circumstances", which promote both clinically effective standards and cost-effective care. Despite controversial discussion about the clinical impact of guidelines, they may provide workable recommendations that may thus be important for improving the individual patient's care. Adverse drug reactions (drug allergies, drug hypersensitivities) often represent a major hazard for the affected patient, and a definite diagnosis is important for further drug therapies in most cases. In this context, any diagnostic procedure must be preceded by an individual risk-benefit assessment. Drug provocation testing is regarded as the gold standard, but this kind of testing should be performed in accordance with established criteria and, in the vast majority of cases, in a hospital setting. In this paper we present a clinical guideline for drug provocation testing in Austria.
Wiener klinische Wochenschrift 09/2011; 123(19-20):585-91. · 0.79 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The term histamine intolerance stands for a range of symptoms involving various effector organs after the consumption of histamine-rich food. Our intention was to objectify and quantify histamine-associated symptoms and to analyse whether oral administration of the histamine-degrading enzyme diamine oxidase (DAO) caused a reduction of symptoms.
Four Austrian centres participated. Patients suspected to be histamine intolerant were recruited. The first step consisted in the open oral provocation of these patients with 75 mg of liquid histamine. Patients who developed symptoms were tested in a randomised double blind crossover provocation protocol using histamine-containing and histamine-free tea in combination with DAO capsules or placebo. Main and secondary symptoms (strongest and weaker symptoms based on a ten-point scale) were defined, the grand total of all symptoms of the individual provocation steps was determined and changes in symptoms after administration of DAO were measured.
Thirty nine patients reacted to the open histamine provocation and were enrolled in the blinded part. Here, both the main and secondary symptoms were not reproducible. Subjects reacted sometimes unexpectedly and randomly. Regarding the total symptom scores, the differences between the three treatment groups were statistically significant. The intake of DAO demonstrated a statistically significant reduction of histamine-associated symptoms compared to placebo (P = 0.014).
Oral provocation with 75 mg of liquid histamine failed to reproduce histamine-associated single symptoms in many patients. One may suggest that histamine-intolerant subjects reacted with different organs on different occasions. As a consequence, reproducibility of single symptoms alone may not be appropriate to diagnose histamine-intolerance whereas a global symptom score could be more appropriate. The fact, that the intake of DAO capsules compared to placebo led to a statistically significant reduction of total symptom scores, may indirectly point in the same direction.
Wiener klinische Wochenschrift 01/2011; 123(1-2):15-20. · 0.79 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Severe side effects during venom immunotherapy (VIT) are associated with a variety of risk factors.
Our aim was to evaluate the association of baseline serum tryptase concentration (BTC) and of other parameters, which are routinely recorded during patient evaluation, with the frequency of severe reactions requiring an emergency intervention during the buildup phase of VIT.
In this observational prospective multicenter study, we enrolled 680 patients with established honeybee or vespid venom allergy who underwent VIT. Data were collected on tryptase concentration, age, sex, culprit insect, cardiovascular medication, degree of preceding sting reaction, preventive antiallergic medication before therapy, time between last preceding sting reaction and VIT, venom specific IgE concentration, and type of buildup procedure. Relative rates were calculated with generalized additive models.
Fifty-seven patients (8.4%) required an emergency intervention during buildup because of a severe systemic reaction. The frequency of interventions increased significantly with higher BTC (log-linear association; adjusted odds ratio, 1.56; 95% CI, 1.15-2.11; P < .005). The predictive power of BTC was markedly greater when VIT was performed for vespid venom allergy than for bee venom (for bee VIT, no significant association; for vespid VIT, log-linear association; adjusted odds ratio, 2.33; 95% CI, 1.28-4.26; P = .005). The most important other factor significantly associated with severe reactions during the buildup phase of VIT was bee venom allergy.
Before vespid VIT, measurement of baseline serum tryptase concentration should be used to identify patients with a high risk for side effects. Patients with bee venom allergy require a particularly high degree of surveillance during VIT.
The Journal of allergy and clinical immunology 07/2010; 126(1):105-11.e5. · 12.05 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Severe anaphylaxis to honeybee or vespid stings is associated with a variety of risk factors, which are poorly defined.
Our aim was to evaluate the association of baseline serum tryptase concentrations and other variables routinely recorded during patient evaluation with the frequency of past severe anaphylaxis after a field sting.
In this observational multicenter study, we enrolled 962 patients with established bee or vespid venom allergy who had a systemic reaction after a field sting. Data were collected on tryptase concentration, age, sex, culprit insect, cardiovascular medication, and the number of preceding minor systemic reactions before the index field sting. A severe reaction was defined as anaphylactic shock, loss of consciousness, or cardiopulmonary arrest. The index sting was defined as the hitherto first, most severe systemic field-sting reaction. Relative rates were calculated with generalized additive models.
Two hundred six (21.4%) patients had a severe anaphylactic reaction after a field sting. The frequency of this event increased significantly with higher tryptase concentrations (nonlinear association). Other factors significantly associated with severe reactions after a field sting were vespid venom allergy, older age, male sex, angiotensin-converting enzyme inhibitor medication, and 1 or more preceding field stings with a less severe systemic reaction.
In patients with honeybee or vespid venom allergy, baseline serum tryptase concentrations are associated with the risk for severe anaphylactic reactions. Preventive measures should include substitution of angiotensin-converting enzyme inhibitors.
The Journal of allergy and clinical immunology 11/2009; 124(5):1047-54. · 12.05 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Allergen-specific subcutaneous immunotherapy (SCIT) is an antigen-specific therapy of IgE-mediated allergies. In the present study, we analyze the epitope specificities of antibody responses induced by SCIT with allergen extracts from pollen of trees belonging to the order Fagales (birch, alder, hazel) adsorbed onto aluminum hydroxide.
The IgE, IgG1-4 and IgA responses to defined recombinant allergens (birch pollen: Bet v 1; alder pollen: Aln g 1; hazel pollen: Cor a 1; apple: Mal d 1) as well as to Bet v 1-derived recombinant fragments and synthetic peptides were analyzed in sera from patients who had undergone SCIT for different periods of time.
Long-term SCIT (>1 year; cumulative dose >1,000,000 SQ units) induced more pronounced IgG1, IgG2 and IgG4 responses to Bet v 1 and Bet v 1-related allergens according to the degree of sequence homology (Bet v 1>Aln g 1>Cor a 1>Mal d 1) than short-term SCIT (<1 year; cumulative dose <1,000,000 SQ units). In contrast to patients treated for <1 year, patients treated for >1 year mounted distinct IgG1, IgG2 and IgG4 responses against sequential Bet v 1 epitopes. No relevant allergen-specific IgA or IgG3 responses were induced by short- or long-term SCIT. Using a competitive ELISA assay, it could be shown that serum IgG from patients undergoing long-term SCIT inhibited IgE reactivity to Bet v 1 better than IgG from patients undergoing short-term SCIT.
SCIT with allergen extracts adsorbed onto aluminum hydroxide induces IgG responses against new epitopes that block IgE binding and cross-react with structurally related allergens depending, among other factors, on duration of treatment and cumulative injected dose.
International Archives of Allergy and Immunology 09/2009; 151(1):17-27. · 2.25 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Previously, we have constructed recombinant derivatives of the major birch pollen allergen, Bet v 1, with a more than 100-fold reduced ability to induce IgE-mediated allergic reactions. These derivatives differed from each other because the two recombinant Bet v 1 fragments represented unfolded molecules whereas the recombinant trimer resembled most of the structural fold of the Bet v 1 allergen. In this study, we analyzed the Ab (IgE, IgG subclass, IgA, IgM) response to Bet v 1, recombinant and synthetic Bet v 1-derived peptides in birch pollen allergic patients who had been vaccinated with the derivatives or adjuvant alone. Furthermore, we studied the induction of IgE-mediated skin responses in these patients using Bet v 1 and Bet v 1 fragments. Both types of vaccines induced a comparable IgG1 and IgG4 response against new sequential epitopes which overlap with the conformational IgE epitopes of Bet v 1. This response was 4- to 5-fold higher than that induced by immunotherapy with birch pollen extract. Trimer more than fragments induced also IgE responses against new epitopes and a transient increase in skin sensitivity to the fragments at the beginning of therapy. However, skin reactions to Bet v 1 tended to decrease one year after treatment in both actively treated groups. We demonstrate that vaccination with folded and unfolded recombinant allergen derivatives induces IgG Abs against new epitopes. These data may be important for the development of therapeutic as well as prophylactic vaccines based on recombinant allergens.
The Journal of Immunology 11/2007; 179(8):5309-16. · 5.36 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Various studies have shown the clinical efficacy of sublingual immunotherapy in grass pollen-induced rhinoconjunctivitis. However, even short-term treatment with grass extracts might cause sensitizations to formerly unrecognized antigens.
To determine whether the antibody profiles are changing in patients receiving a defined grass pollen extract prior to and during the grass pollen season.
A randomized, double blind, placebo-controlled, multicenter phase I/I111 trial was started prior to the commencement of the grass pollen season. Patients with grass pollen allergy were randomly allocated to four groups, and received daily a standardized tablet at different doses. Treatment was started 8 weeks prior to the beginning of the pollen season and stopped at the end of the season. Blood samples were taken at the beginning of the study, at the beginning and the end of the pollen season, and one year after commencement of the study.
At the beginning of the study, all patients tested positive for the major grass pollen allergens, but negative to the minor antigens. In all patients, the degree of antibody reactivity rose considerably after starting active treatment and fell back to the initial values within one year. Immunoglobulin (Ig) E antibodies to the minor antigens remained negative, independent of treatment and seasonal exposure. In contrast to IgE, specific IgG antibodies to all allergens tested revealed no specific trend.
Immunotherapy with grass allergen tablets was accompanied by an increase in grass-specific IgE antibodies, which further increased during pollen exposure, followed by a post-treatment drop in patient- and disease-specific antibodies. During this short course of treatment, no patient developed any additional sensitizations.
Journal of investigational allergology & clinical immunology: official organ of the International Association of Asthmology (INTERASMA) and Sociedad Latinoamericana de Alergia e Inmunología 02/2007; 17(3):131-6. · 2.64 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The high prevalence of latex sensitization in patients with spina bifida (SB) has been attributed to repeated and early exposure to latex products. Other diseases such as gastroschisis/omphalocoele and post-haemorrhagic/congenital hydrocephalus are also associated with repeated and early latex exposure.
The aim of the study was to evaluate whether the high prevalence of latex sensitization in patients with SB is rather related to the underlying disease itself than to disease-associated known risk factors.
We compared children with SB (n=35), children with gastroschisis/omphalocoele (G/O, n=20) and children with post-haemorrhagic/congenital hydrocephalus (PH, n=45). All children with SB and PH had a ventriculo-peritoneal shunt since a very young age. Patients who underwent three or less surgical procedures matched in terms of age, number of operations, atopy and gender distribution, and were analysed for IgE sensitization rates to latex.
In the SB group, 16 of 35 patients (46%) showed elevated latex-specific IgE antibodies in contrast to one of 20 patients (5%) in the G/O group and four of 45 patients (8.9%) in the PH group (P<0.0005 and P<0.005, Fisher's exact test). Comparing matched control groups (<or=3 operations), the effects remained significant (P<0.05 and P<0.01).
This study suggests that the SB population bears a disease-associated propensity for latex sensitization. This effect cannot be explained exclusively by a higher number of operations and differences related to atopy, age or gender.
[Show abstract][Hide abstract] ABSTRACT: Aloe vera has been used as a cosmetic and medical remedy since ancient times and has gained increasing popularity in recent years. Despite its widespread use, reports of allergic reactions are rare. We patch tested 702 consecutive patients with an oily extract from the leaves, Aloe pulvis from the entire plant and concentrated Aloe vera gel. A specially designed questionnaire was used for the use of Aloe vera, reasons and location of application, adverse reactions, occupation, hobbies and atopy. None of the subjects showed any reaction to one of the preparations. 2 components of the plant have to be distinguished: the bark of the leaves contains anthrachinones with pro-peristaltic and potential antibiotic and anticancer properties. Constraints have been imposed due to their considerable toxic potential. Today, mostly the Aloe gel from the center of the leaves is processed. It almost exclusively consists of carbohydrates to which also many medical effects have been attributed. Carbohydrates are not likely to induce contact sensitization, which might explain the outcome of our study. However, this does not justify unrestrained promotion of Aloe products, as scientific studies investigating the claims on its constitutional effects are few in number, and the majority of them have been unable to diminish the intuitive scepticism against miracle cures, like Aloe seems to be.
[Show abstract][Hide abstract] ABSTRACT: Subcutaneous specific immunotherapy (SIT) has been shown to be a causal treatment with long-term efficacy for allergic rhinoconjunctivitis and asthma, and a preventive measure against the development of asthma and new sensitizations. As it is associated with several inconveniences and serious side effects, sublingual immunotherapy (SLIT) has been developed to evade these problems.
The present review of previously published studies on allergic rhinoconjunctivitis aimed to determine the efficacy of SLIT in comparison with subcutaneous treatment and to summarize long-term results of immunotherapy and its effects on the prevention and treatment of asthma and the prevention of new sensitizations.
The effect of SLIT on allergic rhinoconjunctivitis is low to moderate, depends on the allergen used and is more pronounced in adults than in children, in whom a consistent effect has not been demonstrated. Direct comparison with SIT shows conflicting and inconsistent results. Detailed studies on the prevention of asthma and new sensitizations are not available. Consistent effects of asthma treatment on both symptom and medication scores and lung function have not been reported. A quantitative evaluation is not possible due to indistinct inclusion criteria and different outcome criteria. In summary, currently SLIT plays no significant role in the treatment of asthma, apart from children monosensitized to house dust mites in whom it may have low-moderate effects. Only one study deals with the long-term efficacy of SLIT, which demonstrated a persistent positive effect on asthma, whereas data on rhinoconjunctivitis are completely lacking.
Primary and secondary targets of specific immunotherapy have not been answered satisfactorily for the sublingual route. To date, SLIT cannot be recommended as an adequate alternative to the subcutaneous form. Questions regarding the cumulative dose, duration of therapy and immunological mechanisms have also not been answered. The indication should thus be limited to adult patients with pollen-induced rhinoconjunctivitis being unable to perform SIT, e.g. due to significant side effects.
International Archives of Allergy and Immunology 08/2005; 137(3):181-6. · 2.43 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Children with a shunted hydrocephalus are at highest risk for developing an immediate type allergy to latex. Limited data are available for preventive or therapeutical approaches.
To evaluate the effectiveness of latex avoidance, with special regard to status of sensitization and compliance.
In 1995, 131 children with a shunted hydrocephalus were screened for sensitization to latex by skin prick test and determination of specific IgE. Patients and parents were instructed on latex-avoiding strategies. Hospital physicians, family doctors and dentists were advised to perform further surgical and other medical interventions under latex-free conditions. In 2000, 100 of these 131 patients were re-evaluated according to the same testing procedures. Special attention was directed at the extent prophylaxis had been performed.
In 1995, 30/100 patients re-evaluable in 2000 proved sensitized to latex, 70 had negative testing results. In 2000, 64/70 patients were still negative, six had meanwhile developed latex-specific IgE. Seven out of thirty subjects with former positive testing had changes within the same RAST-class, 20 showed a decline of at least one RAST-class, whereas in three cases an increase of latex-specific IgE was found. However, only 34 patients, mainly those being already sensitized, had thoroughly followed both medical and private prophylaxis. Within this group, 16 subjects (47.1%) had improved and another nine (26.5%) were still negative. Only three (8.8%) already previously sensitized patients presented with a further increase of latex-specific IgE. Medical prevention contributed more to the outcome than home prevention. No statistically significant correlation with latex-avoidance was observed, however, in previously unsensitized subjects. Underlying disease, atopy, number of operations, and age did not prove as significant variables.
Secondary prevention results in a decrease of specific IgE in latex-sensitized patients with hydrocephalus. This is due to medical more than home prophylaxis. Sensitization obviously occurs mainly in early childhood, thus primary prevention remains to be the main target.
[Show abstract][Hide abstract] ABSTRACT: IL-12 is a crucial factor in the development and course of allergic diseases. By virtue of their IL-12 production, dendritic cells (DCs) are potent inducers of T(H)1 responses. However, distinct subsets of DCs have also been shown to induce T(H)2 differentiation.
We hypothesized that DCs from atopic and nonatopic individuals might differ in their propensity to skew T-cell responses to either the T(H)1 type or the T(H)2 type. To this end, we investigated the cytokine patterns produced by DCs from atopic and nonatopic individuals, and we attempted to clarify whether this could be due to different DC lineages or, alternatively, to different microenvironmental factors.
DCs were generated from lymphocyte-depleted PBMCs from atopic and nonatopic donors and fully matured with monocyte-conditioned medium. Production of IL-4, IL-5, IL-10, IL-12, and IL-13 in response to CD40 ligation was measured with ELISA. DC subsets were identified in PBMCs from freshly drawn blood by 3-color flow cytometry.
Compared with DCs from healthy donors, monocyte-derived DCs from atopic patients produced less bioactive IL-12 and IL-10. DC production of IL-4, IL-13, and IL-5 was not detected. Relatively more CD123(+) DCs, corresponding to T(H)2-inducing "DC2s," were found in PBMCs from atopic patients.
The data suggest that in addition to the described abnormalities in the patients' T-cell populations, DCs might also critically contribute to the atopic/allergic T(H)1 outcome in the patient and thus to the disease.
Journal of Allergy and Clinical Immunology 02/2002; 109(1):89-95. · 11.25 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background: IL-12 is a crucial factor in the development and course of allergic diseases. By virtue of their IL-12 production, dendritic cells (DCs) are potent inducers of TH1 responses. However, distinct subsets of DCs have also been shown to induce TH2 differentiation. Objective: We hypothesized that DCs from atopic and nonatopic individuals might differ in their propensity to skew T-cell responses to either the TH1 type or the TH2 type. To this end, we investigated the cytokine patterns produced by DCs from atopic and nonatopic individuals, and we attempted to clarify whether this could be due to different DC lineages or, alternatively, to different microenvironmental factors. Methods: DCs were generated from lymphocyte-depleted PBMCs from atopic and nonatopic donors and fully matured with monocyte-conditioned medium. Production of IL-4, IL-5, IL-10, IL-12, and IL-13 in response to CD40 ligation was measured with ELISA. DC subsets were identified in PBMCs from freshly drawn blood by 3-color flow cytometry. Results: Compared with DCs from healthy donors, monocyte-derived DCs from atopic patients produced less bioactive IL-12 and IL-10. DC production of IL-4, IL-13, and IL-5 was not detected. Relatively more CD123+ DCs, corresponding to TH2-inducing “DC2s,” were found in PBMCs from atopic patients. Conclusion: The data suggest that in addition to the described abnormalities in the patients’ T-cell populations, DCs might also critically contribute to the atopic/allergic TH1 outcome in the patient and thus to the disease. (J Allergy Clin Immunol 2002;109:89-95.)
Journal of Allergy and Clinical Immunology 01/2002; 109(1):89-95. · 11.25 Impact Factor