Longitudinal changes in serum soluble C5b-9 levels following immunomodulatory therapy for multisystem inflammatory syndrome in children.

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) is a postinfectious hyperinflammatory condition that can follow a sudden acute respiratory syndrome coronavirus 2 infection. Although several inflammatory markers are used to guide its clinical management, biomarkers that reflect immunomodulatory therapy responses remain limited. PURPOSE: Evaluate intrapatient changes in serum soluble membrane attack complex/C5b-9 levels before and after immunomodulatory therapy in children with MIS-C. METHODS: In this longitudinal observational study, paired serum samples from 100 children diagnosed with MIS-C across 3 tertiary care centers in India were analyzed for soluble C5b-9 (sC5b-9) concentrations before the initiation of immunomodulatory therapy and at clinical recovery. Intrapatient changes were evaluated using paired nonparametric statistical methods. Clinical phenotypes at presentation were documented and explored in relation to baseline sC5b-9 levels. RESULTS: Serum sC5b-9 concentrations significantly declined following immunomodulatory therapy across the cohort (P<0.0001). Elevated pretherapy sC5b-9 levels were observed in patients presenting with shock, multiorgan dysfunction, or cardiac involvement. Although most patients exhibited reduced sC5b-9 levels following therapy, the magnitude of the change varied among individuals, with a subset showing persistently elevated levels at discharge. CONCLUSION: Serum sC5b-9 levels decreased after immunomodulatory therapy in children with MIS-C, suggesting its potential utility as a longitudinal marker of treatment response. The interpretation of absolute concentrations is limited by the serum-based sampling methodology; however, consistent intrapatient trends support further investigations using optimized complement sampling protocols.