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Publications

Journal Article Ahead of print

PubMed: 41998808 DOI: 10.1111/all.70342

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

Allergy

Authors: Lin Hsin, Simone Reinwald, Anouk von Borstel, Pei Mun Aui, Kirsten Deckert, P Mark Hogarth, Laurent Mascarell, Mark Hew, Robyn E O'Hehir, Menno C van Zelm

Affiliations

  • Department of Immunology, School of Translational Medicine, Monash University, Melbourne, Victoria, Australia.
  • Allergy, Asthma and Clinical Immunology, Alfred Health, Melbourne, Victoria, Australia.
  • Department of Immunology, Leiden University Medical Center, Leiden, the Netherlands.
  • Immune Therapies Group, Burnet Institute, Melbourne, Victoria, Australia.
  • Department of Clinical Pathology, the University of Melbourne, Parkville, Victoria, Australia.
  • Innovation & Science Department, Stallergenes Greer, Antony, France.
  • Public Health & Preventive Medicine, Monash University, Melbourne, Victoria, Australia.
  • Department of Immunology, Erasmus MC, University Medical Center, Rotterdam, the Netherlands.

Abstract

BACKGROUND

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.

METHODS

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.

RESULTS

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.

CONCLUSION

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.

MeSH

Dust, Cells, Serum, Sublingual Immunotherapy, Hypersensitivity, Allergens, Immunotherapy, Memory, B-Lymphocytes, Memory B Cells, Dust Mite Allergy, Allergy