Favorable efficacy of rituximab in ANCA-associated vasculitis patients with excessive B cell differentiation

摘要

B cell depletion by rituximab (RTX) is an effective treatment for anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV). However, peripheral B cell phenotypes and the selection criteria for RTX therapy in AAV remain unclear. Phenotypic characterization of circulating B cells was performed by 8-color flow cytometric analysis in 54 newly diagnosed AAV patients (20 granulomatosis with polyangiitis and 34 microscopic polyangiitis). Patients were considered eligible to receive intravenous cyclophosphamide pulse (IV-CY) or RTX. All patients also received high-dose glucocorticoids (GC). We assessed circulating B cell phenotypes and evaluated the efficacy after 6?months of treatment. There were no significant differences in the rate of clinical improvement, relapses, or serious adverse events between patients receiving RTX and IV-CY. The rate of Birmingham Vasculitis Activity Score (BVAS) improvement at 6?months tended to be higher in the RTX group than in the IV-CY group. The proportion of effector or class-switched memory B cells increased in 24 out of 54 patients (44%). The proportions of peripheral T and B cell phenotypes did not correlate with BVAS at baseline. However, among peripheral B cells, the proportion of class-switched memory B cells negatively correlated with the rate of improvement in BVAS at 6?months after treatment initiation (r?=???0.28, p?=?0.04). Patients with excessive B cell differentiation were defined as those in whom the proportion of class-switched memory B cells or IgD?CD27? B cells among all B cells was ?2 SDs higher than the mean in the HCs. The rate of BVAS remission in patients with excessive B cell differentiation was significantly lower than that in patients without. In patients with excessive B cell differentiation, the survival rate, the rate of BVAS-remission, and dose reduction of GC were significantly improved in the RTX group compared to those in the IV-CY group after 6?months of treatment. The presence of excessive B cell differentiation was associated with treatment resistance. However, in patients with circulating B cell abnormality, RTX was effective and increased survival compared to IV-CY. The results suggest that multi-color flow cytometry may be useful to determine the selection criteria for RTX therapy in AAV patients.