Antibodies against Linear Epitopes on the Goodpasture Autoantigen and Kidney Injury

Abstract

Background and objectives Linear epitopes on the Goodpasture autoantigen involved in human anti-glomerular basement membrane (GBM) disease are not fully defined. This study investigated the linear epitopes recognized by circulating antibodies in anti-GBM patients, aiming to identify the potential nephrogenic linear epitopes and their clinical significance. Design, setting, participants, & measurements Sixty-eight patients with anti-GBM disease were enrolled. Twenty-four overlapping linear peptides were synthesized across the whole sequence of the human Goodpasture autoantigen. ELISA detected circulating antibodies against linear epitopes. Their associations with clinical features were further analyzed. Results Antibodies against linear peptides were detected in sera from 55 patients (80.9%). Three major epitopes with high frequencies were identified: P14 (41%), P16 (36.8%), and P18 (57%). P14, a formerly defined T cell epitope, was a mutual B cell epitope. Antibodies against P14 were frequently detected in patients with positive antineutrophil cytoplasmic antibodies (39.3% versus 12.5%; P=0.01). Patients with anti-P16 antibodies presented with higher serum creatinine on diagnosis (665.5±227.2 versus 443.7±296.8 μmol/L; P=0.001) and worse renal outcome during follow-up (hazard ratio, 2.10; 95% confidence interval, 1.10–3.90; P=0.02). The level of anti-P18 antibodies positively correlated with the percentage of crescents in glomeruli (r=0.54; P=0.008). Recognition of P22 was an independent predictor for patient death (hazard ratio, 3.02; 95% confidence interval, 1.20–7.57; P=0.02). Conclusions Antibodies against linear epitopes on the Goodpasture autoantigen could be detected in human anti-GBM disease and were associated with kidney injury. P14 was a mutual T and B cell epitope, implying its nephrogenic role in disease initiation.