Renal Division, Department of Medicine; Institute of Nephrology, Key Laboratory of Renal Disease, Ministry of Health of China; Key Laboratory of CKD Prevention and Treatment, Ministry of Education of China, Peking University First Hospital, Beijing, China.
Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China.
Clin Rheumatol. 2017 Sep;36(9):2087-2094. doi: 10.1007/s10067-017-3692-8. Epub 2017 May 26.
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 E (P4) and E (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.
在相当数量的新月体性肾小球肾炎患者中，同时检测到抗肾小球基底膜 (GBM) 抗体和抗中性粒细胞胞质抗体 (ANCA)。 假定 ANCA 是初始事件，但机制尚不清楚。 在本研究中，我们研究了血清中针对 Goodpasture 自身抗原线性表位的抗体，旨在揭示这两种自身抗体共存的机制。 纳入了 31 名 ANCA 相关性血管炎患者。 合成了跨越 Goodpasture 自身抗原全长序列的 24 个重叠线性肽段。 通过 ELISA 检测血清中针对线性肽段的抗体，并进一步分析其与临床特征的相关性。 在 31 名 ANCA 相关性血管炎患者中，有 25 名（80.6%）血清中存在针对 Goodpasture 自身抗原的线性肽段抗体。 这些抗体可在 50%的肾功能正常（Scr≤133μmol/L）、70%的中度肾功能不全（133μmol/L＜Scr≤600μmol/L）和 94%的肾衰竭（Scr＞600μmol/L）患者中检测到（P=0.032）。 检测到的最高频率的线性肽段是 P4（51.6%）、P14（54.8%）和 P24（54.8%），它们包含了构成 E（P4）和 E（P14）的构象表位的序列，这些表位被抗 GBM 抗体所识别。 抗 P4 抗体的水平与肾小球中新月体的百分比呈正相关（r=0.764，P=0.027）。 抗 P24 抗体阳性的患者在诊断时肾功能不全的发生率明显更高（88.2% vs. 42.9%，P=0.018）。 ANCA 相关性血管炎患者血清中可检测到针对 Goodpasture 自身抗原线性表位的抗体，这些抗体可能介导针对 Goodpasture 自身抗原构象表位的抗体的产生，即抗 GBM 抗体。
