Rituximab induces sustained reduction of pathogenic B cells in patients with peripheral nervous system autoimmunity

Michael A. Maurer, Goran Rakocevic, Carol S. Leung, Isaak Quast, Martin Lukačišin, Norbert Goebels, Christian Münz, Hedda Wardemann, Marinos Dalakas, Jan D. Lünemann

Research output: Contribution to journalArticlepeer-review

50 Scopus citations


The B cell-depleting IgG1 monoclonal antibody rituximab can persistently suppress disease progression in some patients with autoimmune diseases. However, the mechanism underlying these long-term beneficial effects has remained unclear. Here, we evaluated Ig gene usage in patients with anti-myelin- associated glycoprotein (anti-MAG) neuropathy, an autoimmune disease of the peripheral nervous system that is mediated by IgM autoantibodies binding to MAG antigen. Patients with anti-MAG neuropathy showed substantial clonal expansions of blood IgM memory B cells that recognized MAG antigen. The group of patients showing no clinical improvement after rituximab therapy were distinguished from clinical responders by a higher load of clonal IgM memory B cell expansions before and after therapy, by persistence of clonal expansions despite efficient peripheral B cell depletion, and by a lack of substantial changes in somatic hypermutation frequencies of IgM memory B cells. We infer from these data that the effectiveness of rituximab therapy depends on efficient depletion of noncirculating B cells and is associated with qualitative immunological changes that indicate reconfiguration of B cell memory through sustained reduction of autoreactive clonal expansions. These findings support the continued development of B cell-depleting therapies for autoimmune diseases.

Original languageEnglish
Pages (from-to)1393-1402
Number of pages10
JournalJournal of Clinical Investigation
Issue number4
StatePublished - 2 Apr 2012
Externally publishedYes


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