Title |
Increased Risk for Malignancies in 131 Affected CTLA4 Mutation Carriers
|
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Published in |
Frontiers in immunology, September 2018
|
DOI | 10.3389/fimmu.2018.02012 |
Pubmed ID | |
Authors |
David Egg, Charlotte Schwab, Annemarie Gabrysch, Peter D. Arkwright, Edmund Cheesman, Lisa Giulino-Roth, Olaf Neth, Scott Snapper, Satoshi Okada, Michel Moutschen, Philippe Delvenne, Ann-Christin Pecher, Daniel Wolff, Yae-Jean Kim, Suranjith Seneviratne, Kyoung-Mee Kim, Ji-Man Kang, Samar Ojaimi, Catriona McLean, Klaus Warnatz, Maximilian Seidl, Bodo Grimbacher |
Abstract |
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. |
X Demographics
Geographical breakdown
Country | Count | As % |
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France | 1 | 20% |
United States | 1 | 20% |
Malaysia | 1 | 20% |
Switzerland | 1 | 20% |
Unknown | 1 | 20% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 4 | 80% |
Scientists | 1 | 20% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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Unknown | 93 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Researcher | 19 | 20% |
Other | 9 | 10% |
Student > Doctoral Student | 7 | 8% |
Student > Ph. D. Student | 7 | 8% |
Student > Bachelor | 5 | 5% |
Other | 14 | 15% |
Unknown | 32 | 34% |
Readers by discipline | Count | As % |
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Medicine and Dentistry | 29 | 31% |
Immunology and Microbiology | 13 | 14% |
Biochemistry, Genetics and Molecular Biology | 9 | 10% |
Pharmacology, Toxicology and Pharmaceutical Science | 3 | 3% |
Nursing and Health Professions | 2 | 2% |
Other | 4 | 4% |
Unknown | 33 | 35% |