Phenotype, penetrance, and treatment of 133 cytotoxic T-lymphocyte antigen 4-insufficient subjects
dc.date.accessioned | 2019-06-11T05:54:24Z | |
dc.date.available | 2019-06-11T05:54:24Z | |
dc.date.created | 2018-07-21T16:03:35Z | |
dc.date.issued | 2018 | |
dc.identifier.citation | Schwab, Charlotte Gabrysch, Annemarie Olbrich, Peter Patiño, Virginia Warnatz, Klaus Wolff, Daniel Hoshino, Akihiro Kobayashi, Masao Imai, Kohsuke Takagi, Masatoshi Dybedal, Ingunn Haddock, Jamanda A. Sansom, David M. Lucena, Jose M. Seidl, Maximilian Schmitt-Graeff, Annette Reiser, Veronika Emmerich, Florian Frede, Natalie Bulashevska, Alla Salzer, Ulrich Schubert, Desirée Hayakawa, Seiichi Okada, Satoshi Kanariou, Maria Kucuk, Zeynep Yesim Chapdelaine, Hugo Petruzelkova, Lenka Sumnik, Zdenek Sediva, Anna Slatter, Mary Arkwright, Peter D. Cant, Andrew Lorenz, Hanns-Martin Giese, Thomas Lougaris, Vassilios Plebani, Alessandro Price, Christina Sullivan, Kathleen E. Moutschen, Michel Litzman, Jiří Freiberger, Tomas van de Veerdonk, Frank L. Recher, Mike Albert, Michael H. Hauck, Fabian Seneviratne, Suranjith Pachlopnik Schmid, Jana Kolios, Antonios Unglik, Gary Klemann, Christian Speckmann, Carsten Ehl, Stephan Leichtner, Alan Blumberg, Richard Franke, Andre Snapper, Scott Zeissig, Sebastian Cunningham-Rundles, Charlotte Giulino-Roth, Lisa Elemento, Olivier Dückers, Gregor Niehues, Tim Fronkova, Eva Kanderová, Veronika Platt, Craig D. Chou, Janet Chatila, Talal A. Geha, Raif McDermott, Elizabeth Bunn, Su Kurzai, Monika Schulz, Ansgar Alsina, Laia Casals, Ferran Deyà-Martinez, Angela Hambleton, Sophie Kanegane, Hirokazu Tasken, Kjetil Neth, Olaf Grimbacher, Bodo . Phenotype, penetrance, and treatment of 133 cytotoxic T-lymphocyte antigen 4-insufficient subjects. Journal of Allergy and Clinical Immunology. 2018, 1-15 | |
dc.identifier.uri | http://hdl.handle.net/10852/68293 | |
dc.description.abstract | Objective: We sought to characterize the penetrance, clinical features, and best treatment options in 133 CTLA4 mutation carriers. Methods: Genetics, clinical features, laboratory values, and outcomes of treatment options were assessed in a worldwide cohort of CTLA4 mutation carriers. Results: We identified 133 subjects from 54 unrelated families carrying 45 different heterozygous CTLA4 mutations, including 28 previously undescribed mutations. Ninety mutation carriers were considered affected, suggesting a clinical penetrance of at least 67%; median age of onset was 11 years, and the mortality rate within affected mutation carriers was 16% (n = 15). Main clinical manifestations included hypogammaglobulinemia (84%), lymphoproliferation (73%), autoimmune cytopenia (62%), and respiratory (68%), gastrointestinal (59%), or neurological features (29%). Eight affected mutation carriers had lymphoma, and 3 had gastric cancer. An EBV association was found in 6 patients with malignancies. CTLA4 mutations were associated with lymphopenia and decreased T-, B-, and natural killer (NK) cell counts. Successful targeted therapies included application of CTLA-4 fusion proteins, mechanistic target of rapamycin inhibitors, and hematopoietic stem cell transplantation. EBV reactivation occurred in 2 affected mutation carriers after immunosuppression. Conclusions: Affected mutation carriers with CTLA-4 insufficiency can present in any medical specialty. Family members should be counseled because disease manifestation can occur as late as 50 years of age. EBV- and cytomegalovirus-associated complications must be closely monitored. Treatment interventions should be coordinated in clinical trials. | |
dc.language | EN | |
dc.publisher | American Academy of Allergy, Asthma and Immunology | |
dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 International | |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/4.0/ | |
dc.title | Phenotype, penetrance, and treatment of 133 cytotoxic T-lymphocyte antigen 4-insufficient subjects | |
dc.type | Journal article | |
dc.creator.author | Schwab, Charlotte | |
dc.creator.author | Gabrysch, Annemarie | |
dc.creator.author | Olbrich, Peter | |
dc.creator.author | Patiño, Virginia | |
dc.creator.author | Warnatz, Klaus | |
dc.creator.author | Wolff, Daniel | |
dc.creator.author | Hoshino, Akihiro | |
dc.creator.author | Kobayashi, Masao | |
dc.creator.author | Imai, Kohsuke | |
dc.creator.author | Takagi, Masatoshi | |
dc.creator.author | Dybedal, Ingunn | |
dc.creator.author | Haddock, Jamanda A. | |
dc.creator.author | Sansom, David M. | |
dc.creator.author | Lucena, Jose M. | |
dc.creator.author | Seidl, Maximilian | |
dc.creator.author | Schmitt-Graeff, Annette | |
dc.creator.author | Reiser, Veronika | |
dc.creator.author | Emmerich, Florian | |
dc.creator.author | Frede, Natalie | |
dc.creator.author | Bulashevska, Alla | |
dc.creator.author | Salzer, Ulrich | |
dc.creator.author | Schubert, Desirée | |
dc.creator.author | Hayakawa, Seiichi | |
dc.creator.author | Okada, Satoshi | |
dc.creator.author | Kanariou, Maria | |
dc.creator.author | Kucuk, Zeynep Yesim | |
dc.creator.author | Chapdelaine, Hugo | |
dc.creator.author | Petruzelkova, Lenka | |
dc.creator.author | Sumnik, Zdenek | |
dc.creator.author | Sediva, Anna | |
dc.creator.author | Slatter, Mary | |
dc.creator.author | Arkwright, Peter D. | |
dc.creator.author | Cant, Andrew | |
dc.creator.author | Lorenz, Hanns-Martin | |
dc.creator.author | Giese, Thomas | |
dc.creator.author | Lougaris, Vassilios | |
dc.creator.author | Plebani, Alessandro | |
dc.creator.author | Price, Christina | |
dc.creator.author | Sullivan, Kathleen E. | |
dc.creator.author | Moutschen, Michel | |
dc.creator.author | Litzman, Jiří | |
dc.creator.author | Freiberger, Tomas | |
dc.creator.author | van de Veerdonk, Frank L. | |
dc.creator.author | Recher, Mike | |
dc.creator.author | Albert, Michael H. | |
dc.creator.author | Hauck, Fabian | |
dc.creator.author | Seneviratne, Suranjith | |
dc.creator.author | Pachlopnik Schmid, Jana | |
dc.creator.author | Kolios, Antonios | |
dc.creator.author | Unglik, Gary | |
dc.creator.author | Klemann, Christian | |
dc.creator.author | Speckmann, Carsten | |
dc.creator.author | Ehl, Stephan | |
dc.creator.author | Leichtner, Alan | |
dc.creator.author | Blumberg, Richard | |
dc.creator.author | Franke, Andre | |
dc.creator.author | Snapper, Scott | |
dc.creator.author | Zeissig, Sebastian | |
dc.creator.author | Cunningham-Rundles, Charlotte | |
dc.creator.author | Giulino-Roth, Lisa | |
dc.creator.author | Elemento, Olivier | |
dc.creator.author | Dückers, Gregor | |
dc.creator.author | Niehues, Tim | |
dc.creator.author | Fronkova, Eva | |
dc.creator.author | Kanderová, Veronika | |
dc.creator.author | Platt, Craig D. | |
dc.creator.author | Chou, Janet | |
dc.creator.author | Chatila, Talal A. | |
dc.creator.author | Geha, Raif | |
dc.creator.author | McDermott, Elizabeth | |
dc.creator.author | Bunn, Su | |
dc.creator.author | Kurzai, Monika | |
dc.creator.author | Schulz, Ansgar | |
dc.creator.author | Alsina, Laia | |
dc.creator.author | Casals, Ferran | |
dc.creator.author | Deyà-Martinez, Angela | |
dc.creator.author | Hambleton, Sophie | |
dc.creator.author | Kanegane, Hirokazu | |
dc.creator.author | Tasken, Kjetil | |
dc.creator.author | Neth, Olaf | |
dc.creator.author | Grimbacher, Bodo | |
cristin.unitcode | 185,57,0,0 | |
cristin.unitname | Norsk Senter for Molekylærmedisin | |
cristin.ispublished | true | |
cristin.fulltext | postprint | |
cristin.qualitycode | 2 | |
dc.identifier.cristin | 1598195 | |
dc.identifier.bibliographiccitation | info:ofi/fmt:kev:mtx:ctx&ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Journal of Allergy and Clinical Immunology&rft.volume=&rft.spage=1&rft.date=2018 | |
dc.identifier.jtitle | Journal of Allergy and Clinical Immunology | |
dc.identifier.startpage | 1 | |
dc.identifier.endpage | 15 | |
dc.identifier.doi | http://dx.doi.org/10.1016/j.jaci.2018.02.055 | |
dc.identifier.urn | URN:NBN:no-71447 | |
dc.type.document | Tidsskriftartikkel | |
dc.type.peerreviewed | Peer reviewed | |
dc.source.issn | 0091-6749 | |
dc.identifier.fulltext | Fulltext https://www.duo.uio.no/bitstream/handle/10852/68293/2/Manuscript_unmarked.pdf | |
dc.type.version | AcceptedVersion | |
dc.relation.project | NFR/144182 |
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