Activating PIK3CD mutations impair human cytotoxic lymphocyte differentiation and function, and EBV immunity
Germline gain-of function (GOF) mutations in PIK3CD, encoding the catalytic p110Î´ subunit of phosphatidylinositol-3 kinase, result in hyperactivation of the PI3K-AKT-mTOR pathway and underlie a novel inborn error of immunity. Affected individuals exhibit perturbed humoral and cellular immunity, manifesting as recurrent infections, autoimmunity, hepatosplenomegaly, uncontrolled EBV and/or CMV infection, and an increased incidence of B-cell lymphoproliferation and/or lymphoma. Mechanisms underlying disease pathogenesis remain unknown.
|Authors||Edwards ESJ, Bier J, Cole TS, Wong M, Hsu P, Berglund LJ, Boztug K, Lau A, Gostick E, Price DA, O'Sullivan M, Meyts I, Choo S, Gray P, Holland SM, Deenick EK, Uzel G, Tangye SG|
|Responsible Garvan Author|
|Publisher Name||JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY|
|URL link to publisher's version||https://www.ncbi.nlm.nih.gov/pubmed/29800648|