Levels of epitope-specific autoantibodies correlate with renal damage in anti-GBM disease.
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 alpha3(IV)NC1 domain of type IV collagen [alpha3(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 alpha3(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).


CONCLUSIONS
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.
Yang
Rui
R
Renal Division, Department of Medicine, Peking University First Hospital, Institute of Nephrology, Peking University and Key Laboratory of Renal disease, Ministry of Health of China, Beijing 100034, People's Republic of China.
Hellmark
Thomas
T
Zhao
Juan
J
Cui
Zhao
Z
Segelmark
Marten
M
Zhao
Ming-Hui
MH
Wang
Hai-Yan
HY
D000328:Adult; D019867:Anti-Glomerular Basement Membrane Disease / Q000276:immunology* / Q000473:pathology*; D000918:Antibody Specificity; D001323:Autoantibodies / Q000097:blood*; D001324:Autoantigens / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D001485:Basement Membrane / Q000276:immunology; D015331:Cohort Studies; D024141:Collagen Type IV / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D000939:Epitopes / Q000737:chemistry / Q000235:genetics; D005260:Female; D006801:Humans; D007668:Kidney / Q000473:pathology; D007678:Kidney Glomerulus / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D012189:Retrospective Studies; D055815:Young Adult
D001323:Autoantibodies; D001324:Autoantigens; D024141:Collagen Type IV; D000939:Epitopes; D011994:Recombinant Proteins; C051951:antiglomerular basement membrane antibody; C057112:type IV collagen alpha3 chain