Biphasic Effects on Allergen‐Specific Type 2 Memory B Cells Over 18 Months Sublingual Immunotherapy for House Dust Mite Allergy
Allergy, vol. 81, pp. 2172–2183
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.
Authors 10
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Affiliation as printed
Department of Immunology, School of Translational Medicine Monash University Melbourne Victoria Australia
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The Alfred Hospital · Alfred Health · Monash University
Affiliation as printed
Allergy, Asthma and Clinical Immunology, Alfred Health Melbourne Victoria Australia
Department of Immunology, School of Translational Medicine Monash University Melbourne Victoria Australia
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Anouk von Borstel Aachen Department of Immunology Leiden University Medical Center Leiden The Netherlands
Leiden University Medical Center
Affiliation as printed
Department of Immunology Leiden University Medical Center Leiden the Netherlands
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Affiliation as printed
Department of Immunology, School of Translational Medicine Monash University Melbourne Victoria Australia
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The Alfred Hospital · Alfred Health
Affiliation as printed
Allergy, Asthma and Clinical Immunology, Alfred Health Melbourne Victoria Australia
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Burnet Institute · The University of Melbourne · Monash University
Affiliation as printed
Department of Clinical Pathology the University of Melbourne Parkville Victoria Australia
Department of Immunology, School of Translational Medicine Monash University Melbourne Victoria Australia
Immune Therapies Group Burnet Institute Melbourne Victoria Australia
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Affiliation as printed
Innovation & Science Department Stallergenes Greer Antony France
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The Alfred Hospital · Alfred Health · Monash University
Affiliation as printed
Allergy, Asthma and Clinical Immunology, Alfred Health Melbourne Victoria Australia
Public Health & Preventive Medicine Monash University Melbourne Victoria Australia
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The Alfred Hospital · Alfred Health · Monash University
Affiliation as printed
Allergy, Asthma and Clinical Immunology, Alfred Health Melbourne Victoria Australia
Department of Immunology, School of Translational Medicine Monash University Melbourne Victoria Australia
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Menno C. van Zelm corresponding
Erasmus MC · The Alfred Hospital · Alfred Health · Monash University
Affiliation as printed
Allergy, Asthma and Clinical Immunology, Alfred Health Melbourne Victoria Australia
Department of Immunology, Erasmus MC University Medical Center Rotterdam the Netherlands
Department of Immunology, School of Translational Medicine Monash University Melbourne Victoria Australia
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