Details

Autor(en) / Beteiligte

• Somekh, Ido
• Thian, Marini
• Medgyesi, David
• Gülez, Nesrin
• Magg, Thomas
• Gallón Duque, Alejandro
• Stauber, Tali
• Lev, Atar
• Genel, Ferah
• Unal, Ekrem
• Simon, Amos J.
• Lee, Yu Nee
• Kalinichenko, Artem
• Dmytrus, Jasmin
• Kraakman, Michael J.
• Schiby, Ginette
• Rohlfs, Meino
• Jacobson, Jeffrey M.
• Özer, Erdener
• Akcal, Ömer
• Conca, Raffaele
• Patiroglu, Türkan
• Karakukcu, Musa
• Ozcan, Alper
• Shahin, Tala
• Appella, Eliana
• Tatematsu, Megumi
• Martinez-Jaramillo, Catalina
• Chinn, Ivan K.
• Orange, Jordan S.
• Trujillo-Vargas, Claudia Milena
• Franco, José Luis
• Hauck, Fabian
• Somech, Raz
• Klein, Christoph
• Boztug, Kaan

Titel

CD137 deficiency causes immune dysregulation with predisposition to lymphomagenesis

Ist Teil von

• Blood, 2019-10, Vol.134 (18), p.1510-1516

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2019

Link zum Volltext

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• 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. •CD137 deficiency is a novel inborn error of immunity with immune dysregulation and EBV-associated lymphomagenesis.•Our study highlights the key role of CD137 for immune homeostasis with relevance to immunodeficiency and cancer immunotherapy. [Display omitted]