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Mesangial proliferation and deposition of immunoglobulins and complement components within glomerular mesangium was one of the important pathological features of lupus nephritis. Autoantibodies against human mesangial cells could be detected in the sera of patients with IgA nephropathy (IgAN) and Henoch-Schöenlein nephritis. We speculated that autoantibodies against human glomerular mesangial cells might play a role in the development of lupus nephritis. Objective. To screen autoantibodies against human glomerular mesangial cells in sera from patients with lupus nephritis and to identify their target antigens. Methods. Sera were collected from 96 patients with lupus nephritis as well as 25 patients with IgAN and 20 patients with idiopathic membranous nephropathy (IMN). Cell lysates of in vitro cultured human glomerular mesangial cells were used as antigens in Western-blot analysis to detect autoantibodies against human mesangial cells in sera from patients with lupus nephritis as well as IgAN and IMN. The clinical and pathological significance of the autoantibodies were further investigated. Results. Autoantibodies against human mesangial cells could be detected in 94/96 (97.9%) of the sera from patients with lupus nephritis in Western-blot analysis. Twelve protein bands could be blotted by the sera from patients with lupus nephritis. The prevalence of autoantibodies against human mesangial cells in IgAN was 14/25 (56.0%) and only seven protein bands could be blotted. Five autoantibodies (anti-18, 24, 36, 46, and 91 kD) could be detected only in sera from patients with lupus nephritis. In patients with lupus nephritis, some autoantibodies might have some relationship with gender, hematuria, ANA, anti-dsDNA or anti-ENA antibodies. Conclusions. There are autoantibodies directly against heterogeneous antigens of human glomerular mesangial cells in sera from patients with lupus nephritis, and some of them might be associated with different clinical manifestations. [ABSTRACT FROM AUTHOR]

Background. Although the clinical importance of demonstrating the presence of anti-glomerular basement membrane (anti-GBM) antibodies is well established, less is known concerning the clinical utility of measuring the levels of autoantibodies. Two conformational epitopes of anti-GBM antibodies have been defined at residues 17–31 and 127–141 of the α3(IV)NC1 domain of type IV collagen [α3(IV)NC1], which were named as EA and EB, respectively. In order to elucidate the importance of such antibodies, we studied the levels and the epitope specificities of anti-GBM antibodies in a large cohort of Chinese patients with anti-GBM disease. Methods. All patients, with anti-GBM disease and available clinical data, diagnosed at Peking University First Hospital from 1996 to 2005 were included in the present study. Recombinant chimeric proteins containing previously defined epitope regions designated as EA and EB were used to detect anti-GBM antibodies by ELISA. Results were compared and correlated with clinical data collected at the time of diagnosis, biopsy findings and outcome after 1 year of follow-up. Results. A retrospective diagnosis of anti-GBM disease was made in 147 patients. Haemoptysis was recorded for 47% of these cases while 53.5% cases had oliguria or anuria at the time of diagnosis. Among these patients, the levels of anti-GBM antibodies correlated with serum creatinine at diagnosis (P < 0.05 for anti EA, EB and α3(IV)NC1). Oliguric patients had higher levels of autoantibodies than non-oliguric patients, however, the difference being statistically significant only for EB (P < 0.05). Renal biopsies were performed in 66 patients, and it was found that 50 (75.8%) had cresent formation in >85% of the glomeruli. There was a correlation between the percentage of crescents and levels of antibodies, but it was significant only for anti-EA antibodies (P < 0.05). Clinical data regarding the follow-up were available for 102 patients; at the end of 1 year, 88 (86.3%) were either dead or dialysis dependent. The absorbance values of anti-GBM antibodies against both EA and EB were also associated with the subsequent development, death or terminal renal insufficiency (P < 0.05). Conclusion. In this study, patients with high levels of circulating antibodies against the specific epitopes EA and EB had a more severe renal disease at diagnosis as well as a worse prognosis. [ABSTRACT FROM AUTHOR]

Abstract: Anti-GBM disease is a rare autoimmune condition characterized by autoantibodies targeting the α3 chain non-collagen 1 domain of type IV collagen (α3(IV)NC1). Recently, we isolated IgG reacting with α3(IV)NC1 from normal healthy human sera. The current study examined the antigen and epitope specificity of these natural autoantibodies (NAA) using recombinant human α1, 3, 5(IV)NC1 and three constructs expressing, previously defined epitope regions designated EA, EB and S2, in the α1(IV)NC1 background. The NAA preparations reacted with recombinant human α3(IV)NC1 to the same extent as with purified bovine α(IV)NC1, but not with recombinant human α1 and α5(IV)NC1. NAA preparations recognized the three chimeric proteins (EA, EB and S2) yielding similar absorbance values. We conclude that anti-GBM NAA recognize the same major epitopes as anti-GBM antibodies from patients with Goodpasture''s disease. [Copyright &y& Elsevier]