| Literature DB >> 31501153 |
Ido Somekh1,2, Marini Thian3,4,5,6, David Medgyesi4,5, Nesrin Gülez7, Thomas Magg1, Alejandro Gallón Duque1,8, Tali Stauber9,10, Atar Lev9,10, Ferah Genel7, Ekrem Unal11,12, Amos J Simon9,10,13, Yu Nee Lee9,10, Artem Kalinichenko3,4,5, Jasmin Dmytrus3,4,5, Michael J Kraakman3,4,5, Ginette Schiby14, Meino Rohlfs1, Jeffrey M Jacobson15, Erdener Özer16, Ömer Akcal7, Raffaele Conca1, Türkan Patiroglu11, Musa Karakukcu11, Alper Ozcan11, Tala Shahin3,4,5, Eliana Appella1,17, Megumi Tatematsu1, Catalina Martinez-Jaramillo8, Ivan K Chinn18,19, Jordan S Orange18,20, Claudia Milena Trujillo-Vargas8, José Luis Franco8, Fabian Hauck1, Raz Somech9,10, Christoph Klein1, Kaan Boztug3,4,5,6,21.
Abstract
Dysregulated immune responses are essential underlying causes of a plethora of pathologies including cancer, autoimmunity, and immunodeficiency. We here investigated 4 patients from unrelated families presenting with immunodeficiency, autoimmunity, and malignancy. We identified 4 distinct homozygous mutations in TNFRSF9 encoding the tumor necrosis factor receptor superfamily member CD137/4-1BB, leading to reduced, or loss of, protein expression. Lymphocytic responses crucial for immune surveillance, including activation, proliferation, and differentiation, were impaired. Genetic reconstitution of CD137 reversed these defects. CD137 deficiency is a novel inborn error of human immunity characterized by lymphocytic defects with early-onset Epstein-Barr virus (EBV)-associated lymphoma. Our findings elucidate a functional role and relevance of CD137 in human immune homeostasis and antitumor responses.Entities:
Mesh：
Substances：
Year: 2019 PMID： 31501153 PMCID： PMC6839947 DOI： 10.1182/blood.2019000644
Source DB: PubMed Journal: Blood ISSN： 0006-4971 Impact factor: 22.113