Artikel
Intra-renal BAFF heralds the autoimmune cascade in lupus nephritis
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Veröffentlicht: | 29. August 2016 |
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Gliederung
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Background: BAFF (BLyS) is a cytokine of the tumor necrosis factor (TNF) ligand family, mainly produced by hematopoietic cells acting as a potent B cell activator (proliferation/differentiation of B cells). The BLISS studies have demonstrated that blocking BAFF by the human monoclonal antibody belimumab is a valuable therapeutic approach in patients with clinically and serologically active lupus. However, regarding Systemic lupus erythematodes (SLE) the defined sources of BAFF that contributes to the severity of this autoimmune disease are still unclear. Recent findings show that BAFF expression is not restricted to myeloid cells. Since lupus nephritis (LN) is the main cause of morbidity and mortality for patients with SLE, the aim of this study was to investigate, whether renal tubular epithelial cells (TEC) are an important source of BAFF and thus, contribute to the pathogenesis and progression of SLE.
Results: We found using quantitative RT-PCR, Western blotting, immunohistochemistry, Cyto-ELISA and immunofluorescence BAFF expression both in cultured murine and human TEC as well as in situ in the kidney. Moreover, BAFF expression in the kidneys of lupus-prone MRL-Faslpr mice correlated with disease activity while BAFF expression on TEC in biopsies of patients with diffuse proliferative LN showed a correlation with the histopathological activity index. In vitro functional assays revealed an autocrine loop of BAFF with its binding receptors on TEC resulting in a strong induction of CSF-1. Furthermore, we identified divergent effects of BAFF on TEC depending on the surrounding milieu (“inflammatory versus non-inflammatory”).
Conclusion: Taken together, our findings indicate that renal-derived BAFF is an important factor in the pathophysiology of LN and systemic autoimmune disease.