Evaluation of patients applying with autoimmune lymphoproliferative syndrome or similar symptoms through in vitro apoptosis test

Diseases of immune dysregulation is a subgroup of primary immunodeficiencies (PID) which may present with autoimmunity, benign and/or malignant lymphoproliferation, allergic diseases and autoinflammation. Autoimmune lymphoproliferative syndrome (ALPS or Canale-Smith Syndrome) is one of the diseases of immune dysregulation and characterized by chronic lymphoproliferation (lymphadenopathy, splenomegaly), immune cytopenias and increased risk of lymphoma. Defect in apoptosis is an important mechanism in the pathogenesis of the disease. The aim of this study is, to evaluate patients with findings of ALPS with in vitro apoptosis test. The study group consists of 20 patients who applied to Department of Pediatric Immunology between the time period of February 2022 and January 2023. Patients who had multiple autoimmune diseases, splenomegaly and/or lymphadenopathy lasting more than six months that cannot be explained by infection or malignancy, or patients with high vitamin B12 levels or a DNT ratio more than 2.5% were included in the study group. The median age of the patients is 11 years and 70% of them are male. The patients presented with autoimmunity (75%), lymphoproliferation (60%), infection (35%) and allergy (10%). When the patients were reviewed using ALPS diagnostic criteria, eleven were identified as having probable ALPS and nine as having ALPS-like disease. In vitro apoptosis test was evaluated in peripheral blood lymphocyte cells taken from patients and healthy control group. The test was found to be abnormal in two patients, one with homozygous FAS gene mutation, one with homozygous Caspase 8 gene mutation. In vitro apoptosis test was normal in four of the six patients with mutations causing ALPS and ALPS-like disease. The normal results of the in vitro apoptosis test in patients with a genetic diagnosis of ALPS highlight the limits of this test and emphasize the need for additional research and genetic analysis for the disease's definitive diagnosis. Keywords: autoimmune lymphoproliferative syndrome, ALPS, in vitro apoptosis Supporting Institution: Hacettepe University Scientific Research Projects (Project Number 20043)