Munc13-4 deficiency with CD5 downregulation on activated CD8+ T cells

Pediatr Int. 2014 Aug;56(4):605-8. doi: 10.1111/ped.12290.

Abstract

Familial hemophagocytic lymphohistiocytosis (FHL) is characterized by uncontrolled activation of T cells and macrophages and hypercytokinemia. We have recently described a significant increase in a subpopulation of CD8(+) T cells with downregulation of CD5 during the acute phase of FHL type2 (FHL2; perforin deficiency), which declines after successful treatment, with a concomitant reduction in serum cytokine level. This unusual subset of CD8(+) T cells, however, has not been characterized in patients with other subtypes of FHL. Herein, we describe a patient with FHL3 (Munc13-4 deficiency) carrying compound heterozygous mutations in the UNC13D gene. He had high serum levels of pro-inflammatory cytokines and significantly increased activated CD8(+) T cells with downregulation of CD5 during the acute phase, similar to that found in FHL2. This immunophenotypic feature may serve as a useful marker of immune dysregulation in FHL3 in addition to FHL2.

Keywords: CD5; CD8+ T cells; Munc13-4; UNC13D; familial hemophagocytic lymphohistiocytosis.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD5 Antigens / physiology*
  • CD8-Positive T-Lymphocytes / physiology*
  • Down-Regulation*
  • Humans
  • Infant
  • Lymphocyte Activation
  • Lymphohistiocytosis, Hemophagocytic / etiology*
  • Male
  • Membrane Proteins / deficiency*

Substances

  • CD5 Antigens
  • Membrane Proteins
  • UNC13D protein, human

Supplementary concepts

  • Hemophagocytic lymphohistiocytosis, familial, 3