title: Antiviral and regulatory T cell immunity in a patient with stromal interaction molecule 1 deficiency.
abstract: Stromal interaction molecule 1 (STIM1) deficiency is a rare genetic disorder of store-operated calcium entry, associated with a complex syndrome including immunodeficiency and immune dysregulation. The link from the molecular defect to these clinical manifestations is incompletely understood. We report two patients with a homozygous R429C point mutation in STIM1 completely abolishing store-operated calcium entry in T cells. Immunological analysis of one patient revealed that despite the expected defect of T cell proliferation and cytokine production in vitro, significant antiviral T cell populations were generated in vivo. These T cells proliferated in response to viral Ags and showed normal antiviral cytotoxicity. However, antiviral immunity was insufficient to prevent chronic CMV and EBV infections with a possible contribution of impaired NK cell function and a lack of NKT cells. Furthermore, autoimmune cytopenia, eczema, and intermittent diarrhea suggested impaired immune regulation. FOXP3-positive regulatory T (Treg) cells were present but showed an abnormal phenotype. The suppressive function of STIM1-deficient Treg cells in vitro, however, was normal. Given these partial defects in cytotoxic and Treg cell function, impairment of other immune cell populations probably contributes more to the pathogenesis of immunodeficiency and autoimmunity in STIM1 deficiency than previously appreciated.
authors.affiliation: Centre of Chronic Immunodeficiency, University of Freiburg, Freiburg 79106, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Fuchs
authors.forename: Anne
authors.initials: A
authors.lastname: Rensing-Ehl
authors.forename: Carsten
authors.initials: C
authors.lastname: Speckmann
authors.forename: Bertram
authors.initials: B
authors.lastname: Bengsch
authors.forename: Annette
authors.initials: A
authors.lastname: Schmitt-Graeff
authors.forename: Ilka
authors.initials: I
authors.lastname: Bondzio
authors.forename: Andrea
authors.initials: A
authors.lastname: Maul-Pavicic
authors.forename: Thilo
authors.initials: T
authors.lastname: Bass
authors.forename: Thomas
authors.initials: T
authors.lastname: Vraetz
authors.forename: Brigitte
authors.initials: B
authors.lastname: Strahm
authors.forename: Tobias
authors.initials: T
authors.lastname: Ankermann
authors.forename: Melina
authors.initials: M
authors.lastname: Benson
authors.forename: Almuth
authors.initials: A
authors.lastname: Caliebe
authors.forename: Regina
authors.initials: R
authors.lastname: Fölster-Holst
authors.forename: Petra
authors.initials: P
authors.lastname: Kaiser
authors.forename: Robert
authors.initials: R
authors.lastname: Thimme
authors.forename: Wolfgang W
authors.initials: WW
authors.lastname: Schamel
authors.forename: Klaus
authors.initials: K
authors.lastname: Schwarz
authors.forename: Stefan
authors.initials: S
authors.lastname: Feske
authors.forename: Stephan
authors.initials: S
authors.lastname: Ehl
mesh_terms: D006801:Humans; D007109:Immunity / Q000235:genetics*; D007153:Immunologic Deficiency Syndromes / Q000209:etiology; D008565:Membrane Proteins / Q000172:deficiency* / Q000235:genetics; D009363:Neoplasm Proteins / Q000172:deficiency* / Q000235:genetics; D017354:Point Mutation; D000071737:Stromal Interaction Molecule 1; D013602:T-Lymphocytes, Cytotoxic / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000473:pathology; D014780:Viruses / Q000276:immunology
chemical_list: D008565:Membrane Proteins; D009363:Neoplasm Proteins; C103530:STIM1 protein, human; D000071737:Stromal Interaction Molecule 1