Mariam Rabani1, Benjamin Wilde1, Katharina Hübbers1, Shilei Xu1, Andreas Kribben1, Oliver Witzke2, Sebastian Dolff3. 1. Department of Nephrology, University Hospital Essen, University Duisburg-Essen, Hufelandstr. 55, 45147 Essen, Germany. 2. Department of Infectious Diseases, University Hospital Essen, University Duisburg-Essen, Hufelandstr. 55, 45147 Essen, Germany. 3. Department of Infectious Diseases, University Hospital Essen, University Duisburg-Essen, Hufelandstr. 55, 45147 Essen, Germany. Electronic address: sebastian.dolff@uk-essen.de.
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.
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 SLEpatients. This may contribute to an imbalanced B-cell regulation towards effector B-cells which might promote the development of lupus nephritis.
Authors: Xin Ma; Yang Dai; Oliver Witzke; Shilei Xu; Monika Lindemann; Andreas Kribben; Sebastian Dolff; Benjamin Wilde Journal: Front Immunol Date: 2022-02-08 Impact factor: 7.561