Biphasic Effects on Allergen-Specific Type 2 Memory B Cells Over 18 Months Sublingual Immunotherapy for House Dust Mite Allergy.

Abstract

Type 2 memory B cells (Bmem) are the reservoir of pathogenic IgE in allergies. Allergen immunotherapy (AIT) can change the course of disease, but if it involves reprogramming of allergen-reactive Bmem remains unknown. Here, we examine how AIT affects allergen-specific Bmem in house dust mite (HDM) allergic patients. HDM allergic patients were longitudinally evaluated over 18 months with or without sublingual HDM-AIT. Visual analog scores, lung function tests, medication scores, serum IgE, and flowcytometric analysis of Der p 1 and Der p 2-specific Type 2 Bmem were performed at t = 0, 4, 12, and 18 months. Patients on HDM-AIT showed clinical improvement over 18 months with reduced intake of other medications and increases in specific serum IgE, IgG2, and IgG4. Allergen-specific Bmem and the proportions of Type 2 Bmem therein became more abundant at 4 and 12 months and showed upregulation of CD29 and IgG4. At 18 months, the Type 2 Bmem proportions were reduced. A biphasic Bmem response with early phenotypic changes followed by loss of the Type 2 state was observed during 18 months of AIT. As durable unresponsiveness takes 18 months of AIT, deletion of Type 2 Bmem is likely an important step in disease attenuation. Interventions that expedite this outcome may be beneficial in driving remission.