Increased Risk for Malignancies in 131 Affected CTLA4 Mutation Carriers.

Autor:	Egg D; Faculty of Medicine, Center for Chronic Immunodeficiency, Medical Center of the University Hospital, University of Freiburg, Freiburg, Germany., Schwab C; Faculty of Medicine, Center for Chronic Immunodeficiency, Medical Center of the University Hospital, University of Freiburg, Freiburg, Germany., Gabrysch A; Faculty of Medicine, Center for Chronic Immunodeficiency, Medical Center of the University Hospital, University of Freiburg, Freiburg, Germany., Arkwright PD; Royal Manchester Children's Hospital, University of Manchester, Manchester, United Kingdom., Cheesman E; Royal Manchester Children's Hospital, University of Manchester, Manchester, United Kingdom., Giulino-Roth L; Division of Pediatric Hematology/Oncology, Department of Pediatrics, Weill Cornell Medicine, New York, NY, United States., Neth O; Seccion de Infectologia e Inmunopatologia, Unidad de Pediatria, Hospital Virgen del Rocio/Instituto de Biomedicina de Sevilla, Sevilla, Spain., Snapper S; Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Children's Hospital Boston, Boston, MA, United States., Okada S; Department of Pediatrics, Hiroshima University Graduate School of Biomedical & Health Sciences, Hiroshima, Japan., Moutschen M; Department of Infectious Diseases and General Internal Medicine, University Hospital of Liege, Liege, Belgium., Delvenne P; Department of Infectious Diseases and General Internal Medicine, University Hospital of Liege, Liege, Belgium., Pecher AC; Department of Internal Medicine II, University Hospital Tübingen, Tübingen, Germany., Wolff D; Department of Internal Medicine III, University Hospital Regensburg, Regensburg, Germany., Kim YJ; Division of Infectious Diseases and Immunodeficiency, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea., Seneviratne S; Institute of Immunity and Transplantation, Royal Free Hospital, University College London, London, United Kingdom., Kim KM; Department of Pathology & Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea., Kang JM; National Cancer Center, Goyang, South Korea., Ojaimi S; Department of Paediatrics, Monash University, Clayton, VIC, Australia., McLean C; Alfred Health, Prahran, VIC, Australia., Warnatz K; Faculty of Medicine, Center for Chronic Immunodeficiency, Medical Center of the University Hospital, University of Freiburg, Freiburg, Germany., Seidl M; Faculty of Medicine, Center for Chronic Immunodeficiency, Medical Center of the University Hospital, University of Freiburg, Freiburg, Germany., Grimbacher B; Faculty of Medicine, Center for Chronic Immunodeficiency, Medical Center of the University Hospital, University of Freiburg, Freiburg, Germany.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2018 Sep 10; Vol. 9, pp. 2012. Date of Electronic Publication: 2018 Sep 10 (Print Publication: 2018).
DOI:	10.3389/fimmu.2018.02012
Abstrakt:	Background: Cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) is a negative immune regulator on the surface of T cells. In humans, heterozygous germline mutations in CTLA4 can cause an immune dysregulation syndrome. The phenotype comprises a broad spectrum of autoinflammatory, autoimmune, and immunodeficient features. An increased frequency of malignancies in primary immunodeficiencies is known, but their incidence in CTLA-4 insufficiency is unknown. Methods: Clinical manifestations and details of the clinical history were assessed in a worldwide cohort of 184 CTLA4 mutation carriers. Whenever a malignancy was reported, a malignancy-specific questionnaire was filled. Results: Among the 184 CTLA4 mutation carriers, 131 were considered affected, indicating a penetrance of 71.2%. We documented 17 malignancies, which amounts to a cancer prevalence of 12.9% in affected CTLA4 mutation carriers. There were ten lymphomas, five gastric cancers, one multiple myeloma, and one metastatic melanoma. Seven lymphomas and three gastric cancers were EBV-associated. Conclusion: Our findings demonstrate an elevated cancer risk for patients with CTLA-4 insufficiency. As more than half of the cancers were EBV-associated, the failure to control oncogenic viruses seems to be part of the CTLA-4-insufficient phenotype. Hence, lymphoproliferation and EBV viral load in blood should be carefully monitored, especially when immunosuppressing affected CTLA4 mutation carriers.
Databáze:	MEDLINE
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