CD38high/HLA-DR+CD8+ T lymphocytes display pathogen-specific expansion regardless of hemophagocytic lymphohistiocytosis

Eur J Immunol. 2024 Nov;54(11):e2451140. doi: 10.1002/eji.202451140. Epub 2024 Sep 3.

Abstract

The characteristic expansion of T CD38high/HLA-DR+CD8+ lymphocytes observed in hemophagocytic lymphohistiocytosis (HLH) and macrophage activation syndrome (MAS) proved able to distinguish HLH/MAS from sepsis and systemic juvenile idiopathic arthritis. However, the performance of this marker in differentiating HLH/MAS from other pediatric febrile conditions with similar clinical onset and yet entirely different treatments remains unexplored. CD38high/HLA-DR+CD8+ frequencies measured in the peripheral fresh blood of pediatric patients attended for suspicion of HLH/MAS were retrospectively recorded and clinical characteristics were retrieved. CD38high/HLA-DR+CD8+ frequencies in HLH/MAS patients (15 patients; median: 22.0%, IQR: 11.0-49.0%) were compared with those who presented febrile conditions other-than-HLH (28 patients; median: 13.0%, IQR: 3.9-28.7%; p = 0.24). HLH and non-HLH patients were subsequently regrouped based on the presence of an identified infection (22 patients; median: 27.0%, IQR: 15.2-72.1%) and compared with those without infections (21 patients; median: 7.6%, IQR: 3.7-24.3%; p = 0.0035). CD38high/HLA-DR+CD8+ percentages were significantly higher only in the infection group compared with the noninfection one, with a patent pathogen-specific expansion in Epstein-Barr virus primoinfection and visceral leishmaniasis regardless of the presence of HLH. CD38high/HLA-DR+CD8+ frequencies do not appear as an HLH-specific marker as they naturally expand in other clinical situations that are common in childhood and may mimic HLH initial presentation.

Keywords: CD38high/HLA‐DR+CD8+ lymphocytes; Hemophagocytic lymphohistiocytosis; Macrophage activation syndrome.

MeSH terms

  • ADP-ribosyl Cyclase 1* / immunology
  • ADP-ribosyl Cyclase 1* / metabolism
  • Adolescent
  • Arthritis, Juvenile / immunology
  • CD8-Positive T-Lymphocytes* / immunology
  • Child
  • Child, Preschool
  • Female
  • HLA-DR Antigens* / immunology
  • Herpesvirus 4, Human / immunology
  • Humans
  • Infant
  • Lymphohistiocytosis, Hemophagocytic* / diagnosis
  • Lymphohistiocytosis, Hemophagocytic* / immunology
  • Macrophage Activation Syndrome / diagnosis
  • Macrophage Activation Syndrome / immunology
  • Male
  • Membrane Glycoproteins / immunology
  • Retrospective Studies

Substances

  • ADP-ribosyl Cyclase 1
  • HLA-DR Antigens
  • CD38 protein, human
  • Membrane Glycoproteins