Association of epitope spreading of antiglomerular basement membrane antibodies and kidney injury

Abstract

Background and objectives Antiglomerular basement membrane autoantibodies are pathogenic in antiglo-merular basement membrane disease with two major epitopes, EA and EB, on α3 chain of type IV collagen. This study investigated the epitope spectrum of antiglomerular basement membrane autoantibodies, aiming to identify the association between epitope specificity and kidney injury. Design, setting, participants, & measurements All 108 patients with antiglomerular basement membrane disease and complete clinical data were divided into three groups according to renal dysfunction: mild group (n=20) with serum creatitine≤1.5 mg/dl; moderate group (n=22) with serum creatinine=1.5-6.8 mg/dl; severe group (n=66) with serum creatitine≥6.8 mg/dl. Epitope spectrums of antibodies were determined by ELISA, and their associations with kidney damage were analyzed. Sequential serum samples in 40 patients were examined during disease courses. Results EA and EB were recognized in 79.6% and 72.2% of patients, respectively. EA and EB reactions were the lowest in the mild group and higher in the moderate group (EA: 35.0% versus 81.8%, P=0.002; EB: 15.0% versus 68.2%, P=0.001). They were the highest in the severe group (EA: 92.4%, P=0.31; EB: 90.9%, P=0.02). Close association was observed between renal injury and EA and EB reactions. Multivariate Cox regression analysis showed that EB reaction was an independent risk factor for renal failure (hazard ratio=6.91, P=0.02). The recognition for non-EAB remained lowamong groups.No augmentation ofepitope spectrum was shownin serialserum samples. Conclusions Intramolecular epitope spreading might occur before the onset of human antiglomerular basement membrane disease. The autoimmunity to EA and EB, especially EB, was crucial for kidney dysfunction. © 2013 by the American Society of Nephrology.