Role of serum complement C3 in blood–brain barrier injury and prognosis of anti-NMDAR encephalitis

BACKGROUND: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a rare autoimmune disease, with some patients experiencing poor clinical outcomes. Complement activation may contribute to disease progression, but its clinical significance remains unclear. This study investigated the correlation between serum complement C3 with blood–brain barrier (BBB) injury and prognosis in anti-NMDAR encephalitis. METHODS: This retrospective study enrolled 82 patients diagnosed with anti-NMDAR encephalitis at the Tianjin Huanhu Hospital. Spearman correlation analysis was used to assess the relationship between serum C3 level, disease severity, and BBB injury marker albumin quotient (Q-Alb). Binary logistic regression analysis and Cox proportional hazards models were used to investigate independent impact of serum C3 on disease prognosis and relapse. Sensitivity, interaction, and stratification analyses were performed to further verify the reliability of the results. Receiver operating characteristic curves were used to assess diagnostic value of serum C3 level for disease prognosis and relapse. RESULTS: The median follow-up time of this study was 37.70 (24.23–55.72) months. Serum C3 level significantly positively correlated with the initial modified Rankin scale (mRS) scores (r = 0.327, P = 0.003) and Q-Alb (r = 0.307, P = 0.005). Mediation analysis showed that BBB injury mediated the effect of serum C3 on disease severity (P < 0.05). Multivariate logistic regression analysis showed that serum C3 was an independent risk factor for poor prognosis (odds ratio = 1.60, 95% confidence interval [CI] = 1.08–2.39, P = 0.020). Multivariate Cox analysis showed that serum C3 (hazard ratio [HR] = 1.32, 95% CI = 1.04–1.66, P = 0.023) and Q-Alb (HR = 1.14, 95% CI = 1.03–1.26, P = 0.009) were significant predictors of relapse. CONCLUSION: BBB injury mediated the effect of serum C3 on disease severity in patients with anti-NMDAR encephalitis. Serum C3 was an independent risk factor for poor prognosis and disease relapse.