title: Interleukin-2-inducible T-cell kinase (ITK) deficiency - clinical and molecular aspects.
abstract: In patients with underlying immunodeficiency, Epstein-Barr virus (EBV) may lead to severe immune dysregulation manifesting as fatal mononucleosis, lymphoma, lymphoproliferative disease (LPD), lymphomatoid granulomatosis, hemophagocytic lymphohistiocytosis (HLH) and dysgammaglobulinemia. Several newly discovered primary immunodeficiencies (STK4, CD27, MAGT1, CORO1A) have been described in recent years; our group and collaborators were able to reveal the pathogenicity of mutations in the Interleukin-2-inducible T-cell Kinase (ITK) in a cohort of nine patients with most patients presenting with massive EBV B-cell lymphoproliferation. This review summarizes the clinical and immunological findings in these patients. Moreover, we describe the functional consequences of the mutations and draw comparisons with the extensively investigated function of ITK in vitro and in the murine model.
authors.affiliation: Department of Pediatric Oncology, Hematology and Clinical Immunology, Medical Faculty, Center of Child and Adolescent Health, Heinrich-Heine-University, Moorenstraße 5, 40225, Duesseldorf, Germany.
authors.forename: Sujal
authors.initials: S
authors.lastname: Ghosh
authors.forename: Kirsten
authors.initials: K
authors.lastname: Bienemann
authors.forename: Kaan
authors.initials: K
authors.lastname: Boztug
authors.forename: Arndt
authors.initials: A
authors.lastname: Borkhardt
mesh_terms: D017668:Age of Onset; D000818:Animals; D001402:B-Lymphocytes / Q000201:enzymology / Q000473:pathology; D004195:Disease Models, Animal; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism*; D008232:Lymphoproliferative Disorders / Q000201:enzymology* / Q000235:genetics; D011505:Protein-Tyrosine Kinases / Q000172:deficiency* / Q000235:genetics*; D013601:T-Lymphocytes / Q000201:enzymology* / Q000473:pathology
chemical_list: D007376:Interleukin-2; D011505:Protein-Tyrosine Kinases