Article (Scientific journals)
Increased risk for malignancies in 131 affected CTLA4 mutation carriers
Egg, D.; Schwab, C.; Gabrysch, A. et al.
2018In Frontiers in Immunology, 9 (SEP)
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Keywords :
Cancer predisposition; CMV; Combined immunodeficiency; CTLA4; EBV; Malignancy; Primary immunodeficiency
Abstract :
[en] 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. © 2018 Egg, Schwab, Gabrysch, Arkwright, Cheesman, Giulino-Roth, Neth, Snapper, Okada, Moutschen, Delvenne, Pecher, Wolff, Kim, Seneviratne, Kim, Kang, Ojaimi, McLean, Warnatz, Seidl and Grimbacher.
Disciplines :
Immunology & infectious disease
Author, co-author :
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, P. D.;  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 and Health Sciences, Hiroshima, Japan
Moutschen, Michel  ;  Université de Liège - ULiège > Département des sciences cliniques > GIGA-R:Immunopath. - Maladies infect. et médec. inter. gén.
Delvenne, Philippe ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Anatomie et cytologie pathologiques
Pecher, A.-C.;  Department of Internal Medicine II, University Hospital Tübingen, Tübingen, Germany
Wolff, D.;  Department of Internal Medicine III, University Hospital Regensburg, Regensburg, Germany
Kim, Y.-J.;  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, K.-M.;  Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
Kang, J.-M.;  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
More authors (12 more) Less
Language :
English
Title :
Increased risk for malignancies in 131 affected CTLA4 mutation carriers
Publication date :
2018
Journal title :
Frontiers in Immunology
eISSN :
1664-3224
Publisher :
Frontiers Media S.A.
Volume :
9
Issue :
SEP
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 25 February 2019

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