Robust memory responses against influenza vaccination in pemphigus patients previously treated with rituximab.

• Type of Material: Article
• Authors: Alice Cho, Emory Vaccine Center; Bridget Bradley, Emory University; Robert Kauffman, Emory Vaccine Center; Lalita Priyamvada, Emory Vaccine Center; Yevgeniy Kovalenkov, Emory Vaccine Center; Ron Feldman, Emory University; Jens Wrammert, Emory University
• Language: English
• Date: 2017-06-15
• Publisher: American Society for Clinical Investigation
• Publication Version: Final Published Version
• Copyright Statement: © 2017, American Society for Clinical Investigation. JCI Insight is an open access journal. All research content is freely available immediately upon publication.
• Final Published Version (URL): http://dx.doi.org/10.1172/jci.insight.93222
• Title of Journal or Parent Work: JCI insight
• ISSN: 2379-3708
• Volume: 2
• Issue: 12
• Grant/Funding Information: This study was supported by the National Institutes of Health (U19 AI057266) and Centers of Excellence of Influenza Research and Surveillance (HHSN 255200700006Z).; We also thank the Dermatology Foundation for support of our work through a Career Development Award to RF.
• Keywords: Vaccines; Immunology
• Research Categories: Health Sciences, Medicine and Surgery; Health Sciences, Immunology

Abstract

Rituximab is a therapeutic anti-CD20 monoclonal antibody widely used to treat B cell lymphoma and autoimmune diseases, such as rheumatic arthritis, systemic lupus erythematosus, and autoimmune blistering skin diseases (AIBD). While rituximab fully depletes peripheral blood B cells, it remains unclear whether some preexisting B cell memory to pathogens or vaccines may survive depletion, especially in lymphoid tissues, and if these memory B cells can undergo homeostatic expansion during recovery from depletion. The limited data available on vaccine efficacy in this setting have been derived from rituximab-treated patients receiving concomitant chemotherapy or other potent immunosuppressants. Here, we present an in-depth analysis of seasonal influenza vaccine responses in AIBD patients previously treated with rituximab, who generally did not receive additional therapeutic interventions. We found that, despite a lack of influenza-specific memory B cells in the blood, patients mount robust recall responses to vaccination, comparable to healthy controls, both at a cellular and a serological level. Repertoire analyses of plasmablast responses suggest that they likely derive from a diverse pool of tissue-resident memory cells, refractory to depletion. Overall, these data have important implications for establishing an effective vaccine schedule for AIBD patients and the clinical care of rituximab-treated patients in general and contribute to our basic understanding of maintenance of normal and pathogenic human B cell memory.