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 language||English (US)|
|Number of pages||10|
|Journal||Clinical Journal of the American Society of Nephrology|
|State||Published - Mar 7 2013|