Peripheral CD5+ B Cells in Antineutrophil Cytoplasmic Antibody–Associated Vasculitis

Abstract

Objective CD5+ B cells have been conceptualized as a possible surrogate for Breg cells. The aim of the present study was to determine the utility of CD5+ B cells as biomarkers in antineutrophil cytoplasmic antibody–associated vasculitis (AAV). Methods The absolute and relative numbers (percentages) of CD5+ B cells (explanatory variables) were measured longitudinally during 18 months in 197 patients randomized to receive either rituximab (RTX) or cyclophosphamide (CYC) followed by azathioprine (AZA) for the treatment of AAV (Rituximab in ANCA-Associated Vasculitis [RAVE] trial). Outcome variables included disease activity (status of active disease versus complete remission), responsiveness to induction therapy, disease relapse, disease severity, and, in RTX-treated patients, relapse-free survival according to the percentage of CD5+ B cells detected upon B cell repopulation. Results CD5+ B cell numbers were comparable between the treatment groups at baseline. After an initial decline, absolute CD5+ B cell numbers progressively increased in patients in the RTX treatment arm, but remained low in CYC/AZA-treated patients. In both groups, the percentage of CD5+ B cells increased during remission induction and slowly declined thereafter. During relapse, the percentage of CD5+ B cells correlated inversely with disease activity in RTX-treated patients, but not in patients who received CYC/AZA. No significant association was observed between the numbers of CD5+ B cells and induction treatment failure or disease severity. The dynamics of the CD5+ B cell compartment did not anticipate disease relapse. Following B cell repopulation, the percentage of CD5+ B cells was not predictive of time to flare in RTX-treated patients. Conclusion The percentage of peripheral CD5+ B cells might reflect disease activity in RTX-treated patients. However, sole staining for CD5 as a putative surrogate marker for Breg cells did not identify a subpopulation of B cells with clear potential for meaningful clinical use. Adequate phenotyping of Breg cells is required to further explore the value of these cells as biomarkers in AAV.

A Lower Proportion of Regulatory B Cells in Patients with Henoch–Schoenlein Purpura Nephritis

“…We found that the number of Bregs has no correlation with the number of neutrophils (data not shown), suggesting that our findings do not represent a general inflammatory response. Although previous studies have shown that the levels of CD5 + B cells and IL-10 + B cells are decreased in antineutrophil cytoplasmic antibody-associated vasculitis [ 38 – 41 ] and the frequency of IL-10–producing B cells is higher in hepatitis B virus-associated membranous nephropathy [ 42 ], our study is the first to indicate that CD38 + CD19 + B cells and Bregs may participate in the pathogenesis of HSPN.…”

Effector and regulatory B cells in immune-mediated kidney disease

“…However, the predictive utility of measuring CD19 + CD5 + B cell numbers for assessment of disease relapse following either rituximab or conventional cyclophosphamide-based therapy was not validated in an analysis of data from the RAVE trial (3). In fact, the number of CD5 + B cells was found to be highly variable from the time of acute disease to remission and no association with subsequent relapses was observed (118). Paradoxically, clinical trials of B cell depletion agents have not demonstrated benefit in SLE (121,122).…”

Recent pathogenetic advances in ANCA-associated vasculitis

“…Furthermore, patients treated with rituximab who were on low or no maintenance immunosuppression and who had a low or sharply declining repopulation percentage of CD5+ B cells relapsed sooner than patients maintained on high maintenance immunosuppression (median 17 versus 29 months, respectively, P = 0.002). With the presumed intention of validating these findings, Unizony et al recently analyzed absolute and relative numbers of CD5+ B cells from PBMC samples collected from 197 participants in the RAVE trial over 18 months and were unable to identify a significant association with disease severity and/or failure of induction therapy; however, analytic methodologies may have been different [32]. CD5 is one of several cell surface markers that characterize regulatory B cells.…”