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Efficient long‐term depletion of CD20 + B cells by rituximab does not affect gut‐resident plasma cells
Author(s) -
Uzzan Mathieu,
Ko Huaibin M.,
Rosenstein Adam K.,
Pourmand Kamron,
Colombel JeanFrederic,
Mehandru Saurabh
Publication year - 2018
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/nyas.13577
Subject(s) - rituximab , cd20 , affect (linguistics) , term (time) , chemistry , immunology , medicine , antibody , physics , psychology , communication , quantum mechanics
The vast majority of antibody‐producing B cells are located within the gastrointestinal tract and are key players in maintaining homeostasis. The failure of rituximab, a potent B cell–depleting agent, to ameliorate ulcerative colitis in a single clinical trial has dampened enthusiasm to study B cells in patients with inflammatory bowel disease (IBD). However, several lines of evidence suggest that intestinal B cells may be affected in IBD. Additionally, the pathophysiological mechanisms underlying rituximab's lack of efficacy in IBD remain unclear. Here, on the basis of detailed immunophenotyping of a patient who underwent a colonoscopy 6 months after the end of rituximab‐based therapy, we observed that rituximab did not deplete colon‐resident plasma cells (PCs) while ablating all CD20 + B cells in tissues and in the circulation. On the basis of these observations, we propose that one factor underlying the lack of efficacy of rituximab relates to the fact that it does not affect the entire B cell compartment in tissues, sparing the intestinal‐resident PCs while effectively depleting CD20 + B cell populations. Thus, we contend that, despite the results of the Rituximab study, there is a need for more intensive B cell–oriented research in inflammatory disorders, including IBD.