Anti-complement factor H autoantibodies may be protective in lupus nephritis
Anti-complement factor H autoantibodies may be protective in lupus nephritis
复制标题
抗补体 H 因子自身抗体可能对狼疮性肾炎具有保护作用
DOI：
10.1016/j.cca.2020.05.005
复制
发表时间：
2020-09-01
影响因子：
5
通讯作者：
Zhao, Ming-Hui
中科院分区：
文献类型：
--
作者：
Li, Lin-Lin;Tan, Ying;Zhao, Ming-Hui
背景资料：方法：收集120例活动性狼疮性肾炎患者作为发现队列，60例活动性狼疮性肾炎患者作为验证队列，34例无肾损害的系统性红斑狼疮（NR-SLE）患者作为疾病对照，30例健康献血员作为正常对照。ELISA法检测CFH自身抗体及IgG亚类，Western blot法检测CFH抗原表位。用亲和层析柱纯化抗CFH自身抗体，并通过C3 b结合试验和体外辅因子活性试验进一步研究抗CFH自身抗体对CFH生物学功能的干扰。狼疮性肾炎患者抗CFH自身抗体的检出率明显高于健康对照组（8.3%（10/120）vs. 0%（0/30），P = 0.017），发现组和验证组之间无显著差异（8.3%（10/120）vs. 11.7%（7/60），P = 0.268）或发现组和NRSLE组（8.3%（10/120）vs. 11.8%（4/34），P = 0.231）。CFH亚类主要为IgG 2（7/10），主要抗原表位位于CFH的中部（8/10）和N端（7/10）。具有抗CFH自身抗体的患者急性肾损伤的发生率显著降低（0%（0/10）vs. 40.0%（4/10），P = 0.025），血清肌酐水平较低（0.76（0.40，1.06）vs. 1.43（0.46，11.15），mg/dL，P = 0.023），血红蛋白水平较高（113.8 ± 24.63 vs. 90.0 ± 22.53，g/L，P = 0.037）。一项功能研究表明，从狼疮肾炎患者中纯化的抗CFH自身抗体可以提高CFH和C3 b之间的结合，并在体外增强CFH的辅因子activity.Conclusions：抗CFH自身抗体在狼疮肾炎患者中检测到约10%的多表位和IgG 2亚类占优势的患者。抗CFH自身抗体阳性患者的肾损害较轻，纯化的自身抗体在体外可增强CFH的C3 b结合和CFI辅因子活性，提示其对狼疮性肾炎具有保护作用。
Background: This study aimed to investigate the role of anti-CFH autoantibodies in lupus nephritis based on a well-defined cohort.Methods: One hundred twenty patients with biopsy-proven active lupus nephritis were collected as the discovery cohort, sixty patients served as the validation cohort, thirty-four patients with SLE without renal involvement (NR-SLE) were as disease controls, and thirty healthy donors were also included. The anti-CFH autoantibodies and IgG subclasses were detected by ELISA, and epitopes were evaluated by western blot. Anti-CFH autoantibodies were purified by affinity chromatography column, and the interference on the biofunctions of CFH was further studied by the C3b binding assay and cofactor activity assay in vitro.Results: The prevalence of anti-CFH autoantibodies in lupus nephritis was significantly higher than that in healthy controls (8.3% (10/120) vs. 0% (0/30), P = 0.017), and no significant difference was found between the discovery and the validation group (8.3% (10/120) vs. 11.7% (7/60), P = 0.268) or the discovery and the NRSLE group (8.3% (10/120) vs. 11.8% (4/34), P = 0.231). The subclass was mainly IgG2 (7/10), and major epitopes were in the middle (8/10 in SCRs 11-14) and N-terminal (7/10 in SCRs 1-4) regions of CFH. Patients with anti-CFH autoantibodies had a significantly lower prevalence of acute kidney injury (0% (0/10) vs. 40.0%(4/10), P = 0.025), lower serum creatinine levels (0.76 (0.40, 1.06) vs. 1.43 (0.46, 11.15), mg/dL, P = 0.023), and higher hemoglobin levels (113.8 +/- 24.63 vs. 90.0 +/- 22.53, g/L, P = 0.037) than those who were negative after further stratified analysis. A functional study showed that anti-CFH autoantibodies purified from patients with lupus nephritis could improve the binding between CFH and C3b, and also enhance the cofactor activity of CFH in vitro.Conclusions: Anti-CFH autoantibodies were detected in patients with lupus nephritis in approximately 10% of patients with polyepitopes and IgG2 subclass predominance. Patients with anti-CFH autoantibodies presented with milder renal damage, and the purified autoantibodies could enhance the C3b binding and CFI cofactor activity of CFH in vitro, which suggested a protective role in the lupus nephritis.