Role of Der p 1–specific B cells in immune tolerance during 2 years of house dust mite–specific immunotherapy

Abstract

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.

Allergen‐specific immunotherapy boosts allergen‐specific IgD production in house dust mite‐sensitized asthmatic patients

“…allergen-specific IgG4-, IgG2-, and IgA-producing B cells, plasmablasts, IL-10 + IL-1RA + Breg cells and reduced allergen-specific IgE-producing B cells. [4][5][6] In addition, an increase in allergen-specific-IgG4 + B cells was shown to correlate with a reduction in symptom score in successful AIT. 4 Whereas AIT is an effective treatment in the patients with house dust mites (HDM) allergy, the role of HDM allergen-specific IgD remains to be fully evaluated.…”

“…[4][5][6] In addition, an increase in allergen-specific-IgG4 + B cells was shown to correlate with a reduction in symptom score in successful AIT. 4 Whereas AIT is an effective treatment in the patients with house dust mites (HDM) allergy, the role of HDM allergen-specific IgD remains to be fully evaluated. 4,7 The major HDM allergens are represented by Der p/f 1, Der p/f 2, and Der p/f 23.…”

Recent developments and highlights in immune monitoring of allergen immunotherapy

“…It appears that changes in the B‐cell compartment are quite restricted, as despite early reports of more global changes involving transitional and naive mature B cells in atopic dermatitis, these could not be replicated, and do not appear to be affected by AIT . The exception to this would be an increase in IL‐10‐expressing B cells, or Breg, which is associated with tolerance to bee venom and SLIT for grass pollen and HDM allergies …”

“…Typically, increased proportions of Th1 and regulatory T (Treg) cells are seen, 32,33 and cytokines released from these cells are thought to downregulate the Th2 response, 34 as well as driving generation of allergen-specific IgG4 (Figure 2A). 35,36 Together, the modified Th cell response and inhibitory activity of IgG4 antibodies are believed to form the basis of immune tolerance. 6 Several types of assays have been developed in the past years for laboratory testing of immune cells and molecules driving immune tolerance.…”

“…33 The exception to this would be an increase in IL-10-expressing B cells, or Breg, which is associated with tolerance to bee venom and SLIT for grass pollen and HDM allergies. 36,128,129…”