Levels of epitope-specific autoantibodies correlate with renal damage in anti-GBM disease
Open Access
- 16 January 2009
- journal article
- research article
- Published by Oxford University Press (OUP) in Nephrology Dialysis Transplantation
- Vol. 24 (6), 1838-1844
- https://doi.org/10.1093/ndt/gfn761
Abstract
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.Keywords
This publication has 20 references indexed in Scilit:
- Antiglomerular basement membrane disease with normal renal functionKidney International, 2007
- Natural anti-GBM antibodies from normal human sera recognize α3(IV)NC1 restrictively and recognize the same epitopes as anti-GBM antibodies from patients with anti-GBM diseaseClinical Immunology, 2007
- Natural autoantibodies against glomerular basement membrane exist in normal human seraKidney International, 2006
- Detection Rate and Antigenic Specificities of Antineutrophil Cytoplasmic Antibodies in Chinese Patients with Clinically Suspected VasculitisClinical and Vaccine Immunology, 2004
- Characterization of autoantibodies from patients with Goodpasture's disease using a resonant mirror biosensoClinical and Experimental Immunology, 2002
- Identification of a clinically relevant immunodominant region of collagen IV in Goodpasture diseaseKidney International, 1999
- Antiglomerular basement membrane (GBM)-antibody-mediated disease with normal renal functionNephrology Dialysis Transplantation, 1998
- CIGARETTE SMOKING AND LUNG HAEMORRHAGE IN GLOMERULONEPHRITIS CAUSED BY AUTOANTIBODIES TO GLOMERULAR BASEMENT MEMBRANEThe Lancet, 1983
- Recurrence of anti-glomerular basement membrane antibody mediated glomerulonephritis in an isograftClinical Immunology and Immunopathology, 1981
- THE ROLE OF ANTI-GLOMERULAR BASEMENT MEMBRANE ANTIBODY IN THE PATHOGENESIS OF HUMAN GLOMERULONEPHRITISThe Journal of Experimental Medicine, 1967