C3 as a predictive and prognostic biomarker in adult hemophagocytic lymphohistiocytosis: a large cohort study in China

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory syndrome. Complement component 3 (C3), a central effector molecule in 3 separate complement pathways, has been linked to inflammatory diseases. Hence, we aimed to investigate the clinical significance of C3 in adult HLH. In this retrospective cohort study, patients meeting ≥5 of 8 HLH-2004 criteria were classified as the HLH group (n = 627), whereas those meeting 1 to 4 criteria were the partial HLH group (n = 588). C3 was significantly lower in the HLH group than the partial HLH group (P < .0001), and low C3 was an independent factor predicting progression from partial HLH to HLH (odds ratio, 3.94; P < .001). Low C3 was associated with more severe cytopenia, coagulation abnormalities, and liver dysfunction. Additionally, patients with low C3 had poorer overall survival (P = .00099), and low C3 was an independent risk factor for early death in HLH (hazard ratio, 1.64; P = .019). Most patients with HLH had normal C3 before HLH onset, followed by a decline after HLH development (P < .0001). Moreover, survivors showed an increase in C3 (P = .0003), whereas nonsurvivors exhibited a decrease in C3 (P = .90). In conclusion, our study identified C3 as a valuable predictive and prognostic biomarker in adult HLH. Monitoring the dynamic changes in C3 levels may reflect therapeutic response and guide timely clinical interventions.