title: Munc13-4 deficiency with CD5 downregulation on activated CD8+ T cells.
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.
authors.affiliation: Department of Pediatrics, School of Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Japan.
authors.forename: Taizo
authors.initials: T
authors.lastname: Wada
authors.forename: Takahiro
authors.initials: T
authors.lastname: Yasumi
authors.forename: Tomoko
authors.initials: T
authors.lastname: Toma
authors.forename: Masayuki
authors.initials: M
authors.lastname: Hori
authors.forename: Sayaka
authors.initials: S
authors.lastname: Maeda
authors.forename: Katsutsugu
authors.initials: K
authors.lastname: Umeda
authors.forename: Toshio
authors.initials: T
authors.lastname: Heike
authors.forename: Souichi
authors.initials: S
authors.lastname: Adachi
authors.forename: Ikuya
authors.initials: I
authors.lastname: Usami
authors.forename: Akihiro
authors.initials: A
authors.lastname: Yachie
mesh_terms: D018956:CD5 Antigens / Q000502:physiology*; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology*; D015536:Down-Regulation; D006801:Humans; D007223:Infant; D008213:Lymphocyte Activation; D051359:Lymphohistiocytosis, Hemophagocytic / Q000209:etiology*; D008297:Male; D008565:Membrane Proteins / Q000172:deficiency*
chemical_list: D018956:CD5 Antigens; D008565:Membrane Proteins; C507969:UNC13D protein, human
keywords: CD5; CD8+ T cells; Munc13-4; UNC13D; familial hemophagocytic lymphohistiocytosis