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<p>Life-threatening organ dysfunction due to a dysregulated host response to infection defines sepsis, and uncontrolled T-cell activation results in Hemophagocytic lymphohistiocytosis (HLH). Sepsis and HLH share numerous overlapping clinical and laboratory features. To differentiate between sepsis and HLH, we conducted a cross-sectional study on the steroid-naïve adult population (&gt; 16 years) using peripheral blood flow cytometric immunophenotyping. We compared T-cell surface activation markers, viz. HLA-DR and CD38, on CD4 and CD8 T cells among patients with sepsis, HLH and healthy controls. The percentage of CD8⁺CD38⁺ and CD8⁺CD38⁺HLA-DR⁺ T-cell subsets differ significantly between sepsis and HLH. A cut-off of &gt; 46.8% for CD8⁺CD38⁺ and &gt; 14.7% for CD8⁺CD38⁺HLA-DR⁺ achieves a sensitivity of 100%, with specificities of 96.7% and 93.3%, respectively. T-cell surface activation markers show promise in differentiating sepsis from HLH in adults. Larger, multicentric, longitudinal studies are required to validate these results and define their prognostic significance.</p>

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Navigating the Gray Zone: Differentiating Sepsis and Secondary HLH in Adults Using T Cell Activation Markers

  • 期刊论文

  • 发表日期：

    2025年11月7日

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  • Shilpi Saxena,
  • Manisha Madkaikar,
  • Fnu Shweta,
  • Reetika Malik Yadav,
  • Umair A. Bargir,
  • Maya Gupta,
  • Harleen Kaur,
  • Saleem Amjad Mirza,
  • Parikshit Sanyal,
  • Purushotham Godavarthy,
  • Kamal Deep Joshi

摘要

Life-threatening organ dysfunction due to a dysregulated host response to infection defines sepsis, and uncontrolled T-cell activation results in Hemophagocytic lymphohistiocytosis (HLH). Sepsis and HLH share numerous overlapping clinical and laboratory features. To differentiate between sepsis and HLH, we conducted a cross-sectional study on the steroid-naïve adult population (> 16 years) using peripheral blood flow cytometric immunophenotyping. We compared T-cell surface activation markers, viz. HLA-DR and CD38, on CD4 and CD8 T cells among patients with sepsis, HLH and healthy controls. The percentage of CD8⁺CD38⁺ and CD8⁺CD38⁺HLA-DR⁺ T-cell subsets differ significantly between sepsis and HLH. A cut-off of > 46.8% for CD8⁺CD38⁺ and > 14.7% for CD8⁺CD38⁺HLA-DR⁺ achieves a sensitivity of 100%, with specificities of 96.7% and 93.3%, respectively. T-cell surface activation markers show promise in differentiating sepsis from HLH in adults. Larger, multicentric, longitudinal studies are required to validate these results and define their prognostic significance.