Observational studyMedical science monitor : international medical journal of experimental and clinical research2025
Perforin Expression and Natural Killer-Cell Proportion as Biomarkers in Secondary Hemophagocytic Lymphohistiocytosis.
Observational study in Medical science monitor : international medical journal of experimental and clinical research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
BACKGROUND Secondary hemophagocytic lymphohistiocytosis (sHLH) is a life-threatening hyperinflammatory syndrome. The immunopathology of cytotoxic lymphocytes in sHLH is complex and differs from primary HLH. This study aimed to characterize the distribution and perforin expression of key cytotoxic lymphocyte subsets in sHLH and assess their clinical and longitudinal significance. MATERIAL AND METHODS In this single-center observational study, peripheral blood from 19 patients with newly diagnosed sHLH and 10 healthy controls was analyzed using multi-color flow cytometry. Proportions of NK cells, CD8⁺ T cells, and CD56⁺ T cells, along with intracellular perforin expression, were quantified. Six patients were re-assessed after achieving complete response. RESULTS Compared with controls, sHLH patients showed a significantly lower proportion of NK cells, while the percentage of perforin-expressing CD56⁺ T cells was significantly increased. Among sHLH subtypes, NK-cell proportion was significantly lower in lymphoma-associated HLH than in non-lymphoma cases. Longitudinally, CD8⁺ T-cell proportion decreased significantly in patients in remission. NK-cell proportion correlated positively with fibrinogen, a key diagnostic and disease activity marker. Perforin expression in CD56⁺ T cells correlated negatively with alanine aminotransferase, while perforin in CD8⁺ T cells correlated positively with soluble interleukin-2 receptor. CONCLUSIONS sHLH exhibits a distinct immunological profile characterized by reduced NK-cell proportion and increased perforin expression in CD56⁺ T cells, diverging from the primary HLH model. These findings suggest that monitoring cytotoxic lymphocyte dynamics may be valuable for assessing disease activity and treatment response in sHLH, although further validation in larger cohorts is warranted.
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