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Author Notes:

Address correspondence to Jens Wrammert, Department of Pediatrics, Division of infectious Disease, Emory Vaccine Center, School of Medicine, Emory University, 1760 Haygood Drive, HSRB building E480, Atlanta, Georgia 30322, USA. Phone: 404.778.3265; Email: jwramme@emory.edu

AC carried out experiments, analyzed the data, and wrote the manuscript.

BB provided clinical support of the study.

RK, LP, and YK contributed to sample collection and analysis, critical discussion, and editing of this manuscript.

RF and JW conceived the research, oversaw the experiments and data analysis, and wrote and approved the final manuscript.

R. Feldman and J. Wrammert contributed equally to this study.

We thank R. Karaffa and S. Durham at the Emory School of Medicine flow cytometry core and A. Rae at Emory Pediatric’s flow cytometry core for their technical assistance with cell-sorting experiments.

We would also like to thank A. Ellebedy, A. Lowen, and S. Gangappa for providing the influenza virus strains for our experiment.

The authors have declared that no conflict of interest exists.

Subjects:

Research Funding:

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:

  • Immunology
  • Vaccines

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

Tools:

Journal Title:

JCI insight

Volume:

Volume 2, Number 12

Publisher:

Type of Work:

Article | Final Publisher PDF

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.

Copyright information:

© 2017, American Society for Clinical Investigation. JCI Insight is an open access journal. All research content is freely available immediately upon publication.

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