| Autor: |
Fuchs, Sebastian, Rensing-Ehl, Anne, Speckmann, Carsten, Bengsch, Bertram, Schmitt-Graeff, Annette, Bondzio, Ilka, Maul-Pavicic, Andrea, Bass, Thilo, Vraetz, Thomas, Strahm, Brigitte, Ankermann, Tobias, Benson, Melina, Caliebe, Almuth, Fölster-Holst, Regina, Kaiser, Petra, Thimme, Robert, Schamel, Wolfgang W., Schwarz, Klaus, Feske, Stefan, Ehl, Stephan |
| Jazyk: |
angličtina |
| Rok vydání: |
2011 |
| Předmět: |
|
| Popis: |
Stromal interaction molecule 1 (STIM1)4 deficiency is a rare genetic disorder of store-operated Calcium entry (SOCE), 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 2 patients with a homozygous R429C point mutation in STIM1 completely abolishing SOCE 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 antigens 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. Forkhead box protein 3 (FOXP3) positive regulatory T cells (Treg) 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 regulatory T cell function, impairment of other immune cell populations probably contributes more to the pathogenesis of immunodeficiency and autoimmunity in STIM1 deficiency than previously appreciated. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
|
