Characterization of food allergies in patients with atopic dermatitis.

We examined the characteristics of food allergy prevalence and suggested the basis of dietary guidelines for patients with food allergies and atopic dermatitis. A total of 2,417 patients were enrolled in this study. Each subject underwent a skin prick test as well as serum immunoglobulin E (IgE) measurement. A double-blind, placebo-controlled food challenge was conducted using milk, eggs, wheat, and soybeans, and an oral food challenge was performed using beef, pork, and chicken. Food allergy prevalence was found among 50.7% in patients with atopic dermatitis. Among patients with food allergies (n = 1,225), the prevalence of non-IgE-mediated food allergies, IgE-mediated food allergies, and mixed allergies was discovered in 94.9%, 2.2%, and 2.9% of the patients, respectively. Food allergy prevalence, according to food item, was as follows: eggs = 21.6%, milk = 20.9%, wheat = 11.8%, soybeans = 11.7%, chicken = 11.7%, pork = 8.9% and beef = 9.2%. The total number of reactions to different food items in each patient was also variable at 45.1%, 30.6%, 15.3%, 5.8%, 2.2%, and 1.0% for 1 to 6 reactions, respectively. The most commonly seen combination in patients with two food allergies was eggs and milk. The clinical severity of the reactions observed in the challenge test, in the order of most to least severe, were wheat, beef, soybeans, milk, pork, eggs, and chicken. The minimum and maximum onset times of food allergy reactions were 0.2-24 hrs for wheat, 0.5-48 hrs for beef, 1.0-24 hrs for soybeans, 0.7-24 hrs for milk, 3.0-24 hrs for pork, 0.01-72 hrs for eggs, and 3.0-72 hrs for chicken. In our study, we examined the characteristics of seven popular foods. It will be necessary, however, to study a broader range of foods for the establishment of a dietary guideline. Our results suggest that it may be helpful to identify food allergies in order to improve symptoms in patients with atopic dermatitis.

Allergen-specific transforming growth factor-ß-producing CD19+CD5+ regulatory B-cell (Br3) responses in human late eczematous allergic reactions to cow's milk.

CD19(+)CD5(+) regulatory B cells produce transforming growth factor ß (TGF-ß) in both mouse and human B-cell leukemias. In this study, TGF-ß was uniquely produced by normal human regulatory B cells. TGF-ß-producing regulatory B-cell (Br3) responses were characterized through allergic responses to cow's milk. In total, 10 subjects allergic to milk and 13 milk-tolerant subjects were selected following double-blinded, placebo-controlled food challenges. Their peripheral blood mononuclear cells were stimulated in vitro with casein. Following allergen stimulation, the percentage of Br3s among CD5(+) B cells decreased from 11.5% ± 13.7% to 8.0% ± 9.6% (P = 0.042, n = 5) in the milk-allergy group and increased from 14.7% ± 15.6% to 18.9% ± 20.1% (P = 0.006, n = 7) in the milk-tolerant group. However, the numbers of Br3s increased only in the milk-tolerant group, from 1,954 ± 1,058 to 4,548 ± 1,846 per well (P = 0.026), whereas the numbers of Br3s in the milk-allergy group were unchanged [2,596 ± 823 to 2,777 ± 802 per well (P = 0.734)]. The numbers of apoptotic events were similar to the numbers of total Br3 responses. The percentage of non-TGF-ß-producing CD5(+) B cells with apoptotic changes increased from 13.4% ± 17.1% to 16.4% ± 20.3% (P = 0.047, n = 5) in the milk-allergy group and remained unchanged [from 9.9% ± 11.9% to 9.3% ± 11.4% (P = 0.099, n = 7)] in the milk-tolerant group. Using carboxyfluorescein succinimidyl ester labeling, we observed that the percentage of proliferating Br3s among CD5(+) B cells was unchanged [from 6.1% ± 2.8% to 6.4% ± 2.9% (P = 0.145)] in the milk-allergy group and increased from 6.8% ± 3.9% to 10.2% ± 5.3% (P = 0.024) in the milk-tolerant group. In conclusion, Br3s proliferated in response to allergen stimulation in the milk-tolerant group and not in the milk-allergy group. TGF-ß-producing regulatory B cells (Br3) may be involved in allergy tolerance by negatively regulating the immune system with TGF-ß, and this negative regulation may be controlled by apoptosis.

Clinical characteristics of oral tolerance induction of IgE-mediated and non-IgE-mediated food allergy using interferon gamma.

Food allergies are classified as IgE-mediated food allergies (IFAs) and non-IgE-mediated food allergies (NFAs). Recently, oral immunotherapy (OIT) has been found to be successful for treating both IFA and NFA, especially using interferon (IFN) gamma. This study was designed to clarify the clinical characteristics of IFA and NFA and compare the therapeutic characteristics of OIT using subcutaneously administered IFN-gamma for both types of food allergy. In this study, 148 patients were categorized into the IFA and NFA group following food challenge, skin-prick test and food-specific IgE tests. The patients were then treated using protocols specific for IFA and NFA using subcutaneous IFN-gamma injection as a randomized controlled trial. The principle of complete allergy resolution at prior dose in the case of IFA was also evaluated. Only the patients with IFA and NFA treated with OIT using IFN-gamma achieved tolerance successfully. Tolerance was achieved from low-dose range in IFA and in high-dose range for NFA. Complete tolerance was not obtained without achieving complete allergy resolution at each dose of the allergen before increasing the dosage in IFA. Both IFA and NFA can be successfully treated with OIT using IFN-gamma but show different clinical and therapeutic characteristics. IFN-gamma is necessary for the tolerance induction but not for tolerance maintenance. Additional study for the mechanisms of tolerance induction by IFN-gamma is needed.

Characterisation of allergen-specific responses of IL-10-producing regulatory B cells (Br1) in Cow Milk Allergy.

CD19+CD5+ regulatory B cells regulate immune responses by producing IL-10. IL-10-producing regulatory B cell (Br1) responses by allergen stimulation were investigated in human food allergy. Six milk allergy patients and eight milk-tolerant subjects were selected according to DBPCFC. PBMCs were stimulated by casein in vitro and stained for intracellular IL-10 and apoptosis. In response to allergen stimulation, Br1 decreased from 26.2+/-18.3 to 15.5+/-8.9% (p=0.031, n=6) in the milk allergy group and increased from 15.4+/-9.0 to 23.7+/-11.2% (p=0.023, n=8) in the milk-tolerant group. Apoptotic non-IL-10-producing regulatory B cells increased from 21.8+/-9.3 to 38.0+/-16.1% (p=0.031, n=6) in the milk allergy group and unchanged from 28.8+/-13.8 to 28.0+/-15.0% (p=0.844, n=8) in the milk-tolerant group. Br1 may be involved in the immune tolerance of food allergies by producing IL-10 and simultaneously undergoing apoptosis in humans. The exact roles for Br1 in immune tolerance needs to be further investigated.

Allergen-specific B cell subset responses in cow's milk allergy of late eczematous reactions in atopic dermatitis.

B cells have regulatory functions in immune responses. Antigen-specific responses of B cell subsets by allergen stimulation ex vivo were examined in milk allergy of late eczematous reactions. Eight milk allergy subjects and 13 milk tolerant subjects were selected by DBPCFC. PBMCs were stimulated by casein ex vivo and stained for B cell subsets using monoclonal antibodies. CD19+ B cells unchanged from 8.7+/-3.8% to 8.0+/-5.1% (p=0.504, n=8) in the milk allergy group and decreased in the milk tolerant group from 8.5+/-3.2% to 5.0+/-1.6% (p=0.001, n=13). The fraction of apoptotic B cells in B cells significantly decreased 4.4+/-3.1% to 1.3+/-0.4% (p=0.027, n=4) in the allergy group and insignificantly increased from 2.8+/-0.6% to 5.4+/-2.6% (p=0.059, n=6) in the milk tolerant group. CD5+ regulatory B1 cell% in B cells decreased in milk allergy subjects from 36.2+/-5.0% to 31.0+/-5.7% (p=0.010) and unchanged in milk tolerant subjects from 41.6+/-10.2% to 43.8+/-10.0% (p=0.413). IL-10 producing CD19+CD5+ regulatory B cell% in CD19+CD5+ regulatory B cells significantly decreased from 24.9+/-6.5% to 13.8+/-5.6% (p=0.002, n=5) by casein stimulation in milk allergy group and unchanged from 44.8+/-11.3% to 43.9+/-10.0% (p=0.297, n=5) in the milk tolerant group. B cell subset responses to IL-4 and IL-5 were also similar in both groups. B cell subset changes seemed to have diagnostic value. Exact immunologic roles of regulatory CD5+ B1 cells need further investigation.