Background: Long-term follow-up of allergen-specific B cells in terms of immunoglobulin isotype expression, plasmablast differentiation, and regulatory B (Breg) cell development during allergen-specific immunotherapy (AIT) has not been reported. Objective: Allergen-specific B-cell responses during 2 years of house dust mite AIT were compared between responder and nonresponder patients. Methods: B cells specific for Der p 1 were detected by using the fluorochrome-labeled allergen method. The frequency of IgA-, IgG 1-and IgG 4-switched Der p 1-specific B cells, plasmablasts, and IL-10and IL-1 receptor antagonist (IL-1RA)-producing Breg cells were investigated and correlated to clinical response to AIT. Results: Sixteen of 25 patients completed the 2-year study. Eleven responder patients showed a successful response to AIT, as measured by a decrease in symptom-medication scores from 13.23 6 0.28 to 2.45 6 0.24 (P 5 .001) and a decrease in skin prick test reactivity to house dust mite from 7.0 6 1.3 to 2.7 6 0.5 mm (P 5 .001). IgG 4 1 and IgA 1 Der p 1-specific B cells showed a significant increase after AIT, with a significantly greater frequency in responders compared with nonresponders in the IgG 4 1 but not the IgA 1 fraction. The frequency of plasmablasts and IL-10-and/or IL-1RA-producing Breg cells was greater among responders compared with nonresponders after 2 years. The increased frequency of Der p 1-specific IgG4 1 B cells, plasmablasts, and IL-10 1 and dual-positive IL-10 1 IL-1RA 1 Breg cells significantly correlated with improved clinical symptoms over the course of AIT. Conclusion: Allergen-specific B cells in patients responding to AIT are characterized by increased numbers of IgA-and IgG 4expressing Der p 1-specific B cells, plasmablasts, and IL-10 1 and/or IL-1RA 1 Breg cells.

Background: Allergen-specific immunotherapy (AIT) is the only available treatment for allergic diseases that can induce specific immune tolerance to allergens. The key mechanisms involved in this process include changes in allergen-specific regulatory T (Treg) cells. Methods:We studied 25 allergic rhinitis patients undergoing subcutaneous house dust mite-specific immunotherapy. Peripheral blood mononuclear cells were studied before and after 10, 30 weeks, and 3 years of AIT. Der p 1-specific T regulatory cell responses were investigated by characterization of Der p 1-MHC class II tetramerpositive cells and correlated with nasal symptom score. Results: Twelve of 25 AIT patients matched with their MHC class II expression to the Der p 1 peptide-MHC class II tetramers. A significant increase in the numbers of Der p 1-specific FOXP3 + Helios + CD25 + CD127 − Treg cells after 30 weeks was observed, which slightly decreased after 3 years of AIT. In contrast, Der p 1-specific immunoglobulin-like transcript 3 (ILT3) + CD25 + Treg cells decreased substantially from baseline after 3 years of AIT. ILT3 + Treg cells displayed compromised suppressive function and low FOXP3 expression. In addition, Der p 1-specific IL-10 and IL-22 responses have increased after 30 weeks, but only IL-10 + Der p 1-specific Treg cells remained present at high frequency after 3 years of AIT. Increased number of FOXP3 + Helios + and IL-10 + and decreased ILT3 + Treg cell responses correlated with improved allergic symptoms. Conclusion: The results indicate that AIT involves upregulation of the activated allergen-specific Treg cells and downregulation of dysfunctional allergen-specific Treg cell subset. Correction of dysregulated Treg cells responses during AIT is associated with improved clinical response. K E Y W O R D Sallergen-specific T cells, antigen-specific immunotherapy, house dust mite allergy, Treg Abbreviations: AIT, antigen-specific immunotherapy; AR, allergic rhinitis; HDM, house dust mite; ILT3, immunoglobulin-like transcript 3; Treg, T regulatory.

The prevalence of CM adverse reactions was as low as 1.05%. Risk factors consist of a history of previous CM reactions, female gender and seafood allergy. Nevertheless, serious immediate reactions could occur particularly in patients with asthma.

Vitamin D plays an important role in the immune system; decreased serum vitamin D concentrations have been linked to dysregulated immune function. Low vitamin D status is probably associated with chronic spontaneous urticaria (CSU). We evaluated the prevalence of low vitamin D status, and the clinical response and quality of life following vitamin D supplementation, in a prospective case-control study with 60 CSU patients and 40 healthy individuals. Serum 25-hydroxy vitamin D (25(OH)D) concentrations were measured at baseline and after 6 weeks. For patients with 25(OH)D concentrations < 30 ng/ml, treatment included 20,000 IU/day of ergocalciferol (vitamin D2) and non-sedative antihistamine drugs for 6 weeks. Urticaria symptom severity and quality of life were assessed based on the Urticaria Activity Score over 7 days (UAS7) and the Dermatology Life Quality Index (DLQI). Of the 100 participants, 73% were female; the mean age was 39 ± 16 years. Vitamin D deficiency (measured as 25(OH)D < 20 ng/ml) was significantly higher in the CSU group than the control group. The median 25(OH)D concentration for the CSU group, 15 (7 - 52) ng/ml was significantly lower than for control group, 30 (25 - 46) ng/ml. Overall, 83% (50/60) of CSU patients (25(OH)D < 30 ng/ml) were treated with ergocalciferol (vitamin D2) supplementation; after 6 weeks, these patients showed significant improvements in UAS7 and DLQI scores compared with the non-vitamin D supplement group. This study revealed a significant association of lower serum 25(OH)D concentrations with CSU. Vitamin D supplements might improve symptoms and quality of life in CSU patients.

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