| Autor: |
Egg, David, Schwab, Charlotte, Gabrysch, Annemarie, Arkwright, Peter D., Cheesman, Edmund, Giulino-Roth, Lisa, Neth, Olaf, Snapper, Scott, Okada, Satoshi, Moutschen, Michel, Delvenne, Philippe, Pecher, Ann-Christin, Wolff, Daniel, Kim, Yae-Jean, Seneviratne, Suranjith, Kim, Kyoung-Mee, Kang, Ji-Man, Ojaimi, Samar, McLean, Catriona, Warnatz, Klaus |
| Předmět: |
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| Zdroj: |
Frontiers in Immunology; 9/10/2018, pN.PAG-N.PAG, 12p |
| 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. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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