Clinical Spectrum of Patients with Pathogenic Variant of STAT3 conferring Gain-of-Function: A Mimic of Autoimmune Lymphoproliferative Syndrome

Autoimmune lymphoproliferative syndrome (ALPS) is a rare genetic disorder caused by defective fas-mediated apoptosis. Patients often present in childhood with lymphoproliferation, splenomegaly and multilineage cytopenias (Price et al. Natural history of autoimmune lymphoproliferative syndrome associated with FAS gene mutations. Blood 2014). Though mutations in the FAS gene account for the majority of cases, an estimated 20% of patients who have no defined genetic cause are classified as ALPS-U (Shah et al. Autoimmune lymphoproliferative syndrome: an update and review of the literature. Current allergy and asthma reports 2014). Heterozygous STAT3 gain-of-function mutations have been reported to encompass a similar clinical phenotype including expansion of signature cells of ALPS; "double negative" TCR-αβ+T lymphocytes (DNTs) accompanied by solid organ autoimmunity and may represent a proportion of ALPS-U cases (Nabhani et al. STAT3 gain-of-function mutations associated with autoimmune lymphoproliferative syndrome like disease deregulate lymphocyte apoptosis and can be targeted by BH3 mimetic compounds. Clinical Immunology 2017).We identified 12 patients from 10 families with STAT3 gain of functiongenetic variants (Table 1). Here we describe the clinical spectrum of disease of this cohort seen in our institution during the last 15 years with features suggestive of ALPS-like disease.There were 8 males and 4 females. Their median age of symptom onset was 3 years (Range...
Source: Blood - Category: Hematology Authors: Tags: 203. Lymphocytes, Lymphocyte Activation, and Immunodeficiency, including HIV and Other Infections: Poster III Source Type: research