Immunedysregulation of severe fever with thrombocytopenia syndrome patients complicated by hemophagocytic lymphohistiocytosis

We aimed to explore the immunological and clinical characteristics of severe fever with thrombocytopenia syndrome (SFTS) patients complicated with hemophagocytic lymphohistiocytosis (HLH), and to investigate the impact of HLH on disease severity and prognosis. We performed a comprehensive evaluation of laboratory indicators and immunological profiles in 233 SFTS patients. The subsets, activity and cytotoxicity of various immune cells were detected by flow cytometry. Patients with HLH showed reduced blood cell counts and elevated liver enzymes and inflammatory markers, suggesting severe inflammation and organ damage. Immune profiling revealed a decrease in CD3+, CD4+ and CD8+ T cell counts, particularly in those with concurrent HLH. Exhaustion markers on T cells were notably increased and proliferation marker Ki67 was upregulated in T cells, while diminished in NK cells. A decrease in perforin expression among CD8+ T cells suggested dysregulated cytotoxic mechanism. SFTS patients with HLH showed higher SFTSV RNA levels. Multivariate analysis identified HLH and high SFTSV RNA levels as independent predictors of mortality. This study provides the landscape of clinical and immunological characterization of SFTS patients complicated by HLH, revealing concurrent HLH as a critical determinant of disease severity and prognosis.