Comprehensive evaluation of immune dysregulation and altered cytotoxic markers in secondary hemophagocytic lymphohistiocytosis (sHLH)

Abstract

Abstract Background Host immune dysfunction plays a crucial role in the onset, progression, and outcome of hemophagocytic lymphohistiocytosis (HLH). This study aimed to comprehensively evaluate the peripheral immune profiles in patients with newly diagnosed secondary hemophagocytic lymphohistiocytosis (sHLH), and explore their predictive value for patient prognosis. Methods A total of 77 patients with sHLH were enrolled in this study, with 31 of them experiencing mortality. Flow cytometry was used to assess the percentages, absolute numbers, and phenotypes of lymphocyte subsets. Simultaneously, cytokine levels and routine laboratory indicators were also collected. Results In patients with sHLH, the percentages of CD3 + T cells, CD4 + T cells, and NK cells were found to be decreased, while the percentages of CD8 + T cells and B cells were increased compared to healthy controls. Similarly, when compared to disease controls (DCs), the percentages of CD3 + T cells and CD4 + T cells were decreased, while the percentages of NK cells were increased. Furthermore, the absolute numbers of lymphocyte subsets were significantly impaired in sHLH patients. Specifically, a notable decreased in EMRA CD8 + T cells were observed. Additionally, there was a significant increase in the proportion of plasma cells within the B cell population. We further investigated the prognostic value of immune indicators in sHLH. Kaplan-Meier survival analysis revealed that lower levels of CD3 + T cells, higher levels of APTT and IL-6 were associated with a poor prognosis in sHLH patients. Conclusions The lymphocyte subsets in the sHLH group exhibited dysregulation, with significant impairments observed in the absolute numbers of various lymphocyte subsets. Notably, CD3 + T cells and IL-6 were identified as critical markers for predicting prognosis and identifying potential treatment targets in HLH.