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 NR-SLE 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.
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