In a substantial number of patients with crescentic
glomerulonephritis, both anti-glomerular basement membrane (GBM)
antibodies and
anti-neutrophil cytoplasmic antibodies (
ANCA) are detected simultaneously.
ANCA is presumed to be the initial event but the mechanism is unknown. In the present study, we investigated the
antibodies against linear
epitopes on Goodpasture
autoantigen in sera from patients with
ANCA-associated vasculitis, aiming to reveal the mechanisms of the coexistence of the two kinds of
autoantibodies. Thirty-one patients with
ANCA-associated vasculitis were enrolled in this study. Twenty-four overlapping linear
peptides were synthesized across the whole sequence of Goodpasture
autoantigen. Serum
antibodies against linear
peptides were detected by ELISA and their associations with clinical features were further analyzed. Twenty-five out of the thirty-one (80.6%) sera from patients with
ANCA-associated vasculitis possessed
antibodies against linear
peptides on Goodpasture
autoantigen. These
antibodies could be detected in 50% of patients with normal renal function (Scr ≤ 133 μmol/L), 70% of patients with moderate renal dysfunction (133 μmol/L < Scr ≤ 600 μmol/L), and 94% of patients with
renal failure (Scr > 600 μmol/L) (P = 0.032). The highest recognition frequencies were found for
peptides P4 (51.6%), P14 (54.8%), and P24 (54.8%), which contained the sequences that constitute the conformational
epitopes of EA (P4) and EB (P14) recognized by
anti-GBM antibodies. The level of anti-P4
antibodies was positively correlated with the percentage of crescents in glomeruli (r = 0.764, P = 0.027). Patients with anti-P24
antibodies had a significantly higher prevalence of renal dysfunction on diagnosis (88.2 vs. 42.9%, P = 0.018).
Antibodies against linear
epitopes on Goodpasture
autoantigen could be detected in sera of patients with
ANCA-associated vasculitis, which might mediate the production of
antibodies towards the conformational
epitopes on Goodpasture
autoantigen, namely, the
anti-GBM antibodies.