IL-21 dependent Granzyme B production of B-cells is decreased in patients with lupus nephritis

Abstract Objectives B-cells play a crucial role in the pathogenesis of lupus nephritis. Recently, a separate subset has been discovered characterized by expression of Granzyme B. The aim of this study is to investigate this subset in patients with systemic lupus erythematosus (SLE). Methods Isolated PBMCs of SLE-patients (n = 30) and healthy controls (n = 21) were in vitro stimulated with CPG, IgG + IgM and IL-21. Patients were sub-grouped in patients with and without biopsy proven lupus nephritis. B-cells were analyzed for intracellular Granzyme B expression by flow cytometry. Results The strongest stimulus for Granzyme B secretion of B-cells was IgG + IgM in presence of IL-21. SLE-patients had a significant decreased percentage of Granzyme B + B-cells in particular SLE-patients with active disease and with lupus nephritis. Conclusions The frequency of GrB + producing B-cells is reduced in SLE patients. This may contribute to an imbalanced B-cell regulation towards effector B-cells which might promote the development of lupus nephritis.