Ya-Chiao Hu1, I-Jung Tsai1, Hui-Yao Hsu1, Bor-Luen Chiang1,2, Yao-Hsu Yang3,4. 1. Department of Pediatrics, National Taiwan University Hospital, College of Medicine, National Taiwan University, No. 7 Chung-Shan South Road, Taipei, Taiwan. 2. Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan. 3. Department of Pediatrics, National Taiwan University Hospital, College of Medicine, National Taiwan University, No. 7 Chung-Shan South Road, Taipei, Taiwan. yan0126@ms15.hinet.net. 4. Department of Pediatrics, National Taiwan University Hospital, Hsin-Chu Branch, Hsinchu, Taiwan. yan0126@ms15.hinet.net.
Abstract
BACKGROUND: The pathogenesis of lupus nephritis (LN) remains not fully understood. In this study, we aimed to explore the pathogenic roles of autoantibodies against human renal glomerular endothelial cells (HRGEC) in LN patients. METHODS: The serum levels of anti-HRGEC antibodies in systemic lupus erythematosus (SLE) patients without LN and LN patients were determined by cell-based enzyme-linked immunosorbent assay (ELISA). Monoclonal IgG anti-HRGEC antibodies were subsequently generated from LN patients. The binding activities of these monoclonal antibodies to HRGEC, their cross-reactivity with double-stranded DNA (dsDNA), and the ability to activate HRGEC were further evaluated. RESULTS: LN patients had higher serum levels of IgG anti-HRGEC antibodies than SLE patients without LN and healthy controls. Four monoclonal IgG anti-HRGEC antibodies (LN1-4) were obtained; LN1 and LN2 were IgG3 while LN3 and LN4 were IgG1. Among these monoclonal antibodies, LN1-3 were cross-reactive with dsDNA. The functional assays showed that compared with IgG1/IgG3 isotype controls, LN3 had an effect on HRGEC to enhance interleukin (IL)-6 production, LN4 could enhance IL-8 and monocyte chemoattractant protein (MCP)-1 production, and LN1-3 possessed the ability to induce interferon (IFN)-α production by HRGEC. Moreover, the removal of DNA on the HRGEC surface by DNAse 1 did not interpose the binding of LN1-3 to HRGEC and the effects of LN1-3 on IFN-α induction by HRGEC. CONCLUSIONS: Some IgG anti-HRGEC antibodies in LN patients had the ability to enhance endothelial proinflammatory cytokine (IL-6, IL-8, and MCP-1) production, and some could induce the DNA-independent production of IFN-α by HRGEC.
BACKGROUND: The pathogenesis of lupus nephritis (LN) remains not fully understood. In this study, we aimed to explore the pathogenic roles of autoantibodies against humanrenal glomerular endothelial cells (HRGEC) in LN patients. METHODS: The serum levels of anti-HRGEC antibodies in systemic lupus erythematosus (SLE) patients without LN and LN patients were determined by cell-based enzyme-linked immunosorbent assay (ELISA). Monoclonal IgG anti-HRGEC antibodies were subsequently generated from LN patients. The binding activities of these monoclonal antibodies to HRGEC, their cross-reactivity with double-stranded DNA (dsDNA), and the ability to activate HRGEC were further evaluated. RESULTS: LN patients had higher serum levels of IgG anti-HRGEC antibodies than SLEpatients without LN and healthy controls. Four monoclonal IgG anti-HRGEC antibodies (LN1-4) were obtained; LN1 and LN2 were IgG3 while LN3 and LN4 were IgG1. Among these monoclonal antibodies, LN1-3 were cross-reactive with dsDNA. The functional assays showed that compared with IgG1/IgG3 isotype controls, LN3 had an effect on HRGEC to enhance interleukin (IL)-6 production, LN4 could enhance IL-8 and monocyte chemoattractant protein (MCP)-1 production, and LN1-3 possessed the ability to induce interferon (IFN)-α production by HRGEC. Moreover, the removal of DNA on the HRGEC surface by DNAse 1 did not interpose the binding of LN1-3 to HRGEC and the effects of LN1-3 on IFN-α induction by HRGEC. CONCLUSIONS: Some IgG anti-HRGEC antibodies in LN patients had the ability to enhance endothelial proinflammatory cytokine (IL-6, IL-8, and MCP-1) production, and some could induce the DNA-independent production of IFN-α by HRGEC.
Authors: M R Ehrenstein; D R Katz; M H Griffiths; L Papadaki; T H Winkler; J R Kalden; D A Isenberg Journal: Kidney Int Date: 1995-09 Impact factor: 10.612
Authors: D V Vlahakos; M H Foster; S Adams; M Katz; A A Ucci; K J Barrett; S K Datta; M P Madaio Journal: Kidney Int Date: 1992-06 Impact factor: 10.612