CD137 deficiency causes immune dysregulation with predisposition to lymphomagenesis.

Autor:	Somekh I; Dr. von Hauner Children's Hospital, University Hospital, Ludwig Maximilian University of Munich, Munich, Germany.; Department of Pediatric Hematology Oncology, Schneider Children's Medical Center of Israel, Petah Tikva, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel., Thian M; St. Anna Children's Cancer Research Institute (CCRI), Vienna, Austria.; Ludwig Boltzmann Institute for Rare and Undiagnosed Diseases, Vienna, Austria.; CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.; Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria., Medgyesi D; Ludwig Boltzmann Institute for Rare and Undiagnosed Diseases, Vienna, Austria.; CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria., Gülez N; Division of Pediatric Immunology and Allergy, S.B.Ü. Dr. Behçet Uz Children's Education And Research Hospital, Izmir, Turkey., Magg T; Dr. von Hauner Children's Hospital, University Hospital, Ludwig Maximilian University of Munich, Munich, Germany., Gallón Duque A; Dr. von Hauner Children's Hospital, University Hospital, Ludwig Maximilian University of Munich, Munich, Germany.; Group of Primary Immunodeficiencies, School of Medicine, University of Antioquia (UdeA), Medellín, Colombia., Stauber T; Pediatric Department A and Immunology Service, Jeffrey Modell Foundation Center, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel HaShomer, Sackler Faculty of Medicine, Tel Aviv University, Israel.; The Wohl Institute for Translational Medicine, Sheba Medical Center, Tel HaShomer, Israel., Lev A; Pediatric Department A and Immunology Service, Jeffrey Modell Foundation Center, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel HaShomer, Sackler Faculty of Medicine, Tel Aviv University, Israel.; The Wohl Institute for Translational Medicine, Sheba Medical Center, Tel HaShomer, Israel., Genel F; Division of Pediatric Immunology and Allergy, S.B.Ü. Dr. Behçet Uz Children's Education And Research Hospital, Izmir, Turkey., Unal E; Department of Pediatrics, Division of Pediatric Hematology Oncology and HSCT Unit, Erciyes University, Faculty of Medicine, Melikgazi, Kayseri, Turkey.; Molecular Biology and Genetic Department, Gevher Nesibe Genom and Stem Cell Institution, Genome and Stem Cell Center (GENKOK), Erciyes University, Melikgazi, Kayseri, Turkey., Simon AJ; Pediatric Department A and Immunology Service, Jeffrey Modell Foundation Center, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel HaShomer, Sackler Faculty of Medicine, Tel Aviv University, Israel.; The Wohl Institute for Translational Medicine, Sheba Medical Center, Tel HaShomer, Israel.; Haematology Laboratory., Lee YN; Pediatric Department A and Immunology Service, Jeffrey Modell Foundation Center, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel HaShomer, Sackler Faculty of Medicine, Tel Aviv University, Israel.; The Wohl Institute for Translational Medicine, Sheba Medical Center, Tel HaShomer, Israel., Kalinichenko A; St. Anna Children's Cancer Research Institute (CCRI), Vienna, Austria.; Ludwig Boltzmann Institute for Rare and Undiagnosed Diseases, Vienna, Austria.; CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria., Dmytrus J; St. Anna Children's Cancer Research Institute (CCRI), Vienna, Austria.; Ludwig Boltzmann Institute for Rare and Undiagnosed Diseases, Vienna, Austria.; CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria., Kraakman MJ; St. Anna Children's Cancer Research Institute (CCRI), Vienna, Austria.; Ludwig Boltzmann Institute for Rare and Undiagnosed Diseases, Vienna, Austria.; CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria., Schiby G; Department of Pathology, and., Rohlfs M; Dr. von Hauner Children's Hospital, University Hospital, Ludwig Maximilian University of Munich, Munich, Germany., Jacobson JM; Radiology Department, Sheba Medical Center, Tel HaShomer, Sackler Faculty of Medicine, Tel Aviv University, Israel., Özer E; Department of Pathology, School of Medicine, Dokuz Eylul University, Izmir, Turkey., Akcal Ö; Division of Pediatric Immunology and Allergy, S.B.Ü. Dr. Behçet Uz Children's Education And Research Hospital, Izmir, Turkey., Conca R; Dr. von Hauner Children's Hospital, University Hospital, Ludwig Maximilian University of Munich, Munich, Germany., Patiroglu T; Department of Pediatrics, Division of Pediatric Hematology Oncology and HSCT Unit, Erciyes University, Faculty of Medicine, Melikgazi, Kayseri, Turkey., Karakukcu M; Department of Pediatrics, Division of Pediatric Hematology Oncology and HSCT Unit, Erciyes University, Faculty of Medicine, Melikgazi, Kayseri, Turkey., Ozcan A; Department of Pediatrics, Division of Pediatric Hematology Oncology and HSCT Unit, Erciyes University, Faculty of Medicine, Melikgazi, Kayseri, Turkey., Shahin T; St. Anna Children's Cancer Research Institute (CCRI), Vienna, Austria.; Ludwig Boltzmann Institute for Rare and Undiagnosed Diseases, Vienna, Austria.; CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria., Appella E; Dr. von Hauner Children's Hospital, University Hospital, Ludwig Maximilian University of Munich, Munich, Germany.; Ricardo Gutiérrez Children's Hospital, Buenos Aires, Argentina., Tatematsu M; Dr. von Hauner Children's Hospital, University Hospital, Ludwig Maximilian University of Munich, Munich, Germany., Martinez-Jaramillo C; Group of Primary Immunodeficiencies, School of Medicine, University of Antioquia (UdeA), Medellín, Colombia., Chinn IK; Center for Human Immunobiology, Texas Children's Hospital, Houston, TX.; Department of Pediatrics, Baylor College of Medicine, Houston, TX., Orange JS; Center for Human Immunobiology, Texas Children's Hospital, Houston, TX.; Department of Pediatrics, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY; and., Trujillo-Vargas CM; Group of Primary Immunodeficiencies, School of Medicine, University of Antioquia (UdeA), Medellín, Colombia., Franco JL; Group of Primary Immunodeficiencies, School of Medicine, University of Antioquia (UdeA), Medellín, Colombia., Hauck F; Dr. von Hauner Children's Hospital, University Hospital, Ludwig Maximilian University of Munich, Munich, Germany., Somech R; Pediatric Department A and Immunology Service, Jeffrey Modell Foundation Center, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel HaShomer, Sackler Faculty of Medicine, Tel Aviv University, Israel.; The Wohl Institute for Translational Medicine, Sheba Medical Center, Tel HaShomer, Israel., Klein C; Dr. von Hauner Children's Hospital, University Hospital, Ludwig Maximilian University of Munich, Munich, Germany., Boztug K; St. Anna Children's Cancer Research Institute (CCRI), Vienna, Austria.; Ludwig Boltzmann Institute for Rare and Undiagnosed Diseases, Vienna, Austria.; CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.; Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria.; Department of Pediatrics and Adolescent Medicine, St. Anna Children's Hospital, Medical University of Vienna, Vienna, Austria.
Jazyk:	angličtina
Zdroj:	Blood [Blood] 2019 Oct 31; Vol. 134 (18), pp. 1510-1516.
DOI:	10.1182/blood.2019000644
Abstrakt:	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. (© 2019 by The American Society of Hematology.)
Databáze:	MEDLINE
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