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Increased Risk for Malignancies in 131 Affected CTLA4 Mutation Carriers

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 imm...

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Autores principales: 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, Seidl, Maximilian, Grimbacher, Bodo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6140401/
https://www.ncbi.nlm.nih.gov/pubmed/30250467
http://dx.doi.org/10.3389/fimmu.2018.02012
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author 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
Seidl, Maximilian
Grimbacher, Bodo
author_facet 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
Seidl, Maximilian
Grimbacher, Bodo
author_sort Egg, David
collection PubMed
description 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.
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spelling pubmed-61404012018-09-24 Increased Risk for Malignancies in 131 Affected CTLA4 Mutation Carriers 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 Seidl, Maximilian Grimbacher, Bodo Front Immunol Immunology 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. Frontiers Media S.A. 2018-09-10 /pmc/articles/PMC6140401/ /pubmed/30250467 http://dx.doi.org/10.3389/fimmu.2018.02012 Text en Copyright © 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. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
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
Seidl, Maximilian
Grimbacher, Bodo
Increased Risk for Malignancies in 131 Affected CTLA4 Mutation Carriers
title Increased Risk for Malignancies in 131 Affected CTLA4 Mutation Carriers
title_full Increased Risk for Malignancies in 131 Affected CTLA4 Mutation Carriers
title_fullStr Increased Risk for Malignancies in 131 Affected CTLA4 Mutation Carriers
title_full_unstemmed Increased Risk for Malignancies in 131 Affected CTLA4 Mutation Carriers
title_short Increased Risk for Malignancies in 131 Affected CTLA4 Mutation Carriers
title_sort increased risk for malignancies in 131 affected ctla4 mutation carriers
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6140401/
https://www.ncbi.nlm.nih.gov/pubmed/30250467
http://dx.doi.org/10.3389/fimmu.2018.02012
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