1. IL-21 dependent Granzyme B production of B-cells is decreased in patients with lupus nephritis.
- Author
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Rabani M, Wilde B, Hübbers K, Xu S, Kribben A, Witzke O, and Dolff S
- Subjects
- Adult, Antigens, CD19 immunology, Antigens, CD19 metabolism, B-Lymphocytes immunology, B-Lymphocytes metabolism, Cells, Cultured, Female, Granzymes metabolism, Humans, Immunoglobulin G immunology, Immunoglobulin G pharmacology, Immunoglobulin M immunology, Immunoglobulin M pharmacology, Interleukins immunology, Lupus Erythematosus, Systemic metabolism, Lupus Nephritis metabolism, Male, Middle Aged, Receptors, Interleukin-21 immunology, Receptors, Interleukin-21 metabolism, B-Lymphocytes drug effects, Granzymes immunology, Interleukins pharmacology, Lupus Erythematosus, Systemic immunology, Lupus Nephritis immunology
- 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., (Copyright © 2017 Elsevier Inc. All rights reserved.)- Published
- 2018
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