{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T01:03:08Z","timestamp":1792458188535,"version":"4.5.0"},"reference-count":58,"publisher":"American Society of Hematology","issue":"23","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,12,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Biallelic mutations in the genes encoding CD27 or its ligand CD70 underlie inborn errors of immunity (IEIs) characterized predominantly by Epstein-Barr virus (EBV)-associated immune dysregulation, such as chronic viremia, severe infectious mononucleosis, hemophagocytic lymphohistiocytosis (HLH), lymphoproliferation, and malignancy. A comprehensive understanding of the natural history, immune characteristics, and transplant outcomes has remained elusive. Here, in a multi-institutional global collaboration, we collected the clinical information of 49 patients from 29 families (CD27, n = 33; CD70, n = 16), including 24 previously unreported individuals and identified a total of 16 distinct mutations in CD27, and 8 in CD70, respectively. The majority of patients (90%) were EBV+ at diagnosis, but only \u223c30% presented with infectious mononucleosis. Lymphoproliferation and lymphoma were the main clinical manifestations (70% and 43%, respectively), and 9 of the CD27-deficient patients developed HLH. Twenty-one patients (43%) developed autoinflammatory features including uveitis, arthritis, and periodic fever. Detailed immunological characterization revealed aberrant generation of memory B and T cells, including a paucity of EBV-specific T cells, and impaired effector function of CD8+ T cells, thereby providing mechanistic insight into cellular defects underpinning the clinical features of disrupted CD27\/CD70 signaling. Nineteen patients underwent allogeneic hematopoietic stem cell transplantation (HSCT) prior to adulthood predominantly because of lymphoma, with 95% survival without disease recurrence. Our data highlight the marked predisposition to lymphoma of both CD27- and CD70-deficient patients. The excellent outcome after HSCT supports the timely implementation of this treatment modality particularly in patients presenting with malignant transformation to lymphoma.<\/jats:p>","DOI":"10.1182\/blood.2020006738","type":"journal-article","created":{"date-parts":[[2020,6,30]],"date-time":"2020-06-30T20:45:01Z","timestamp":1593549901000},"page":"2638-2655","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":100,"title":["Extended clinical and immunological phenotype and transplant outcome in CD27 and CD70 deficiency"],"prefix":"10.1182","volume":"136","author":[{"given":"Sujal","family":"Ghosh","sequence":"first","affiliation":[{"name":"Department of Pediatric Oncology, Hematology and Clinical Immunology, Medical Faculty, Center of Child and Adolescent Health, Heinrich-Heine-University, D\u00fcsseldorf, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3718-5323","authenticated-orcid":false,"given":"Sevgi","family":"K\u00f6stel Bal","sequence":"additional","affiliation":[{"name":"Ludwig Boltzmann Institute for Rare and Undiagnosed Diseases, Vienna, Austria;"},{"name":"St. Anna Children\u2019s Cancer Research Institute (CCRI), Vienna, Austria;"},{"name":"CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0240-4370","authenticated-orcid":false,"given":"Emily S. J.","family":"Edwards","sequence":"additional","affiliation":[{"name":"Garvan Institute of Medical Research, Darlinghurst, NSW, Australia;"},{"name":"St. Vincent\u2019s Clinical School, UNSW Sydney, Randwick, NSW, Australia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bethany","family":"Pillay","sequence":"additional","affiliation":[{"name":"Garvan Institute of Medical Research, Darlinghurst, NSW, Australia;"},{"name":"St. Vincent\u2019s Clinical School, UNSW Sydney, Randwick, NSW, Australia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ra\u00fal","family":"Jim\u00e9nez Heredia","sequence":"additional","affiliation":[{"name":"Ludwig Boltzmann Institute for Rare and Undiagnosed Diseases, Vienna, Austria;"},{"name":"St. Anna Children\u2019s Cancer Research Institute (CCRI), Vienna, Austria;"},{"name":"CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9718-7507","authenticated-orcid":false,"given":"Funda","family":"Erol Cipe","sequence":"additional","affiliation":[{"name":"Department of Pediatric Allergy and Immunology, Istinye University, Istanbul, Turkey;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geetha","family":"Rao","sequence":"additional","affiliation":[{"name":"Garvan Institute of Medical Research, Darlinghurst, NSW, Australia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth","family":"Salzer","sequence":"additional","affiliation":[{"name":"Ludwig Boltzmann Institute for Rare and Undiagnosed Diseases, Vienna, Austria;"},{"name":"St. Anna Children\u2019s Cancer Research Institute (CCRI), Vienna, Austria;"},{"name":"CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria;"},{"name":"St. Anna Children\u2019s Hospital, Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9015-4446","authenticated-orcid":false,"given":"Samaneh","family":"Zoghi","sequence":"additional","affiliation":[{"name":"Ludwig Boltzmann Institute for Rare and Undiagnosed Diseases, Vienna, Austria;"},{"name":"St. Anna Children\u2019s Cancer Research Institute (CCRI), Vienna, Austria;"},{"name":"CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria;"},{"name":"Research Center for Immunodeficiencies, Children\u2019s Medical Center, Tehran University of Medical Sciences, Tehran, Iran;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4838-0407","authenticated-orcid":false,"given":"Hassan","family":"Abolhassani","sequence":"additional","affiliation":[{"name":"Research Center for Immunodeficiencies, Children\u2019s Medical 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A.","family":"Price","sequence":"additional","affiliation":[{"name":"Division of Infection and Immunity, School of Medicine, Cardiff University, Cardiff, United Kingdom;"},{"name":"Vaccine Research Center,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Immunology and Microbiology, Division of Intramural Research,"},{"name":"Clinical Genomics Program, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6310-0434","authenticated-orcid":false,"given":"Andrew J.","family":"Oler","sequence":"additional","affiliation":[{"name":"Clinical Genomics Program, and"},{"name":"Bioinformatics and Computational Biosciences Branch, Office of Cyber Infrastructure and Computational Biology, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health, Bethesda, MD;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4667-3679","authenticated-orcid":false,"given":"Claudia","family":"Gonzaga-Jauregui","sequence":"additional","affiliation":[{"name":"Regeneron Genetics Center, Tarrytown, NY;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9398-8465","authenticated-orcid":false,"given":"Baran","family":"Erman","sequence":"additional","affiliation":[{"name":"Institute of Child Health, Hacettepe University, Ankara, Turkey;"},{"name":"Can Sucak Research Laboratory for Translational Immunology, Center for Genomics and Rare Diseases, Hacettepe University, Ankara, Turkey;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0731-5799","authenticated-orcid":false,"given":"Ayse","family":"Metin","sequence":"additional","affiliation":[{"name":"Division of Pediatric Allergy and Immunology, University of Health 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Turkey;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kubra","family":"Baskin","sequence":"additional","affiliation":[{"name":"Department of Pediatric Allergy and Immunology, School of Medicine, Ankara University, Ankara, Turkey;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2786-1911","authenticated-orcid":false,"given":"Serdar","family":"Ceylaner","sequence":"additional","affiliation":[{"name":"Intergen Genetic Diagnosis and Research Center, Ankara, Turkey;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4802-0986","authenticated-orcid":false,"given":"Ebru","family":"Yilmaz","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Pediatric Hematology & Oncology & Molecular Biology and Genetic Department, Erciyes University, Kayseri, Turkey;"},{"name":"Gevher Nesibe Genom and Stem Cell Institution, GENKOK Genome and Stem Cell Center, Erciyes University, Kayseri, Turkey;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2691-4826","authenticated-orcid":false,"given":"Ekrem","family":"Unal","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Pediatric Hematology & Oncology & Molecular Biology and Genetic Department, Erciyes University, Kayseri, Turkey;"},{"name":"Gevher Nesibe Genom and Stem Cell Institution, GENKOK Genome and Stem Cell Center, Erciyes University, Kayseri, Turkey;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2015-3541","authenticated-orcid":false,"given":"Musa","family":"Karakukcu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Pediatric Hematology & Oncology & Molecular Biology and Genetic Department, Erciyes University, Kayseri, Turkey;"},{"name":"Gevher Nesibe Genom and Stem Cell Institution, GENKOK Genome and Stem Cell Center, 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