Decreased CD5+B cells in active ANCA vasculitis and relapse after rituximab

Donna O'Dell Bunch, Julieanne G. McGregor, Nirmal B. Khandoobhai, Lydia T. Aybar, Madelyn E. Burkart, Yichun Hu, Susan L. Hogan, Caroline J. Poulton, Elisabeth A. Berg, Ronald J. Falk, Patrick H. Nachman

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63 Scopus citations

Abstract

Background and objectives B cell significance in ANCA disease pathogenesis is underscored by the finding that ANCA alone can cause disease in mouse models and by the effectiveness of rituximab as therapy in ANCA-small vessel vasculitis (ANCA-SVV). To avoid infections and adverse events from therapy, clinicians require improved markers of disease activity and impending relapse to guide immunosuppression strategies after rituximab treatment. Design, setting, participants, & measurements The B cell phenotype was investigated in patients with active ANCA-SVV and in remission. From 2003 to 2009, 54 patients were followed longitudinally for 4-99 months and compared with 68 healthy controls. In a subset of 19 patients, the B cell immunophenotype was examined in samples after rituximab therapy. Results Patients with active ANCA-SVV had lower %CD5+ B cells, whereas %CD5+ B cells from patients in remission were indistinguishable from healthy controls. After rituximab, median time to relapse was 31 months in patients maintaining normalized %CD5+ B cells, with or without maintenance immunosuppression. Among patients whose B cells repopulated with low %CD5+ B cells or had a sharply declining %CD5+ B cells, those who were on low or no maintenance immunosuppression relapsed sooner (median 17 months) than patients who were maintained on high levels of oral maintenance immunosuppression (29 months; P=0.002). Conclusions The %CD5+ B cells, as a component of the human B regulatory cell phenotype, is a useful indicator of disease activity, remission, and future relapse, and thus may guide remission maintenance therapy after rituximab treatment.

Original languageEnglish (US)
Pages (from-to)382-391
Number of pages10
JournalClinical Journal of the American Society of Nephrology
Volume8
Issue number3
DOIs
StatePublished - Mar 7 2013
Externally publishedYes

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