Serum epitope-specific anti-recoverin autoantibodies as biomarkers for lupus retinopathy

Lupus retinopathy (LR) is a sight-threatening complication of systemic lupus erythematosus (SLE), yet disease-specific serologic biomarkers are lacking. Previous studies have shown that anti-recoverin (RCV) antibodies act as a biomarker of cancer-associated retinopathy and serum level of anti-RCV antibodies was elevated in SLE patients with fundus abnormalities. This study screened three candidate epitopes of RCV protein and evaluated anti-RCV epitope-specific autoantibodies as candidate serological markers for LR. The epitopes of RCV protein were predicted by DNAStar software and cross-checked by BepiPred-2.0 and ABCpred. Serum autoantibodies against RCV and three linear epitopes (RCV55–70, RCV139–154, RCV155–170) was determined by ELISA in SLE patients with LR (n = 48), without LR (non-LR, n = 48), and healthy controls (HC, n = 44). Statistical analyses included the Kruskal–Wallis with Dunn’s post-hoc tests, Mann-Whitney U test, Student’s t test, Chi-Square or Fisher’s exact tests, correlation analysis, logistic regression, and ROC analysis. Epitope-specific anti-RCV antibodies were significantly higher in LR than in non-LR SLE and HC (all p < 0.05). Anti-RCV139–154 demonstrated the highest diagnostic performance for identifying LR from SLE, with an AUC of 0.808 (95% CI: 0.721–0.895), a sensitivity of 54.2% and a specificity of 93.8%, outperforming full-length anti-RCV. Furthermore, anti-RCV139–154 levels positively correlated with SLE disease activity (SLEDAI, r = 0.430, p < 0.001), anti-dsDNA titers, and IgG levels, and inversely correlated with C3 and C4 levels (p < 0.001). Notably, anti-RCV139–154 levels were preferentially elevated in microvasculopathic LR and declined after treatment. Epitope-specific anti-RCV antibodies, especially anti-RCV139–154, may serve as novel biomarkers for early identification of LR in SLE patients.