Early phenotypic and soluble markers of T cell activity can distinguish sepsis associated HLH from sepsis in children

Abstract

Sepsis associated Hemophagocytic Lymphohistiocytosis (SHLH) is an underrecognized fatal complication of sepsis which requires early diagnosis and aggressive immunosuppressive treatment. However, overlapping clinical symptoms between sepsis and SHLH makes the early diagnosis challenging. Few recent studies have indicated the utility of immune signatures in distinguishing sepsis from HLH due to various underlying triggers. In this cross-sectional study, we evaluated the proportions of T cell subsets, their activation status (% of HLADR+CD38+ or PD1+ T cells) and cytokine profile within 72 hours of diagnosing the children with sepsis. Among the sepsis children, SHLH were identified if ≥4 HLH-2004 criteria are fulfilled. We report a lower CD4:CD8 ratio, and higher percentages of activated (HLADR+CD38+ or PD1+) CD4 T cells in SHLH children than those with sepsis. We also report an increase in the cytokines/chemokines related to T cell activity (IL-2Ra, IFN-g, MIG/CXCL9 and IL-10) in SHLH. ROC analysis revealed a 100% sensitivity and 78% specificity with CD4:CD8 <1.28 and an 87% sensitivity and 93% specificity with PD1+ CD4 Tcells >23.75% supporting the utility of these immune profiles in differentiating sepsis from SHLH early during the disease. Other markers (HLADR+CD38+CD4+T cells, serum levels of IL2Ra, IL-10 and MIG) also showed a specificity of 81-87%. In conclusion, the PD1+/HLADR+CD38+CD4+T cells, CD4:CD8 ratio, IL-2Ra and IL-10 either individually or together are likely to offer a good diagnostic accuracy in early diagnosis of SHLH from sepsis in children.