Publication:
Extended clinical and immunological phenotype and transplant outcome in CD27 and CD70 deficiency

Simple item page
dc.contributor.authorÖZEN, AHMET OĞUZHAN
dc.contributor.authorsGhosh, Sujal; Bal, Sevgi Koestel; Edwards, Emily S. J.; Pillay, Bethany; Heredia, Raul Jimenez; Cipe, Funda Erol; Rao, Geetha; Salzer, Elisabeth; Zoghi, Samaneh; Abolhassani, Hassan; Momen, Tooba; Gostick, Emma; Price, David A.; Zhang, Yu; Oler, Andrew J.; Gonzaga-Jauregui, Claudia; Erman, Baran; Metin, Ayse; Ilhan, Inci; Haskologlu, Sule; Islamoglu, Candan; Baskin, Kubra; Ceylaner, Serdar; Yilmaz, Ebru; Unal, Ekrem; Karakukcu, Musa; Berghuis, Dagmar; Cole, Theresa; Gupta, Aditya K.; Hauck, Fabian; Kogler, Hubert; Hoepelman, Andy I. M.; Baris, Safa; Karakoc-Aydiner, Elif; Ozen, Ahmet; Kager, Leo; Holzinger, Dirk; Paulussen, Michael; Krueger, Renate; Meisel, Roland; Oommen, Prasad T.; Morris, Emma; Neven, Benedicte; Worth, Austen; van Montfrans, Joris; Fraaij, Pieter L. A.; Choo, Sharon; Dogu, Figen; Davies, E. Graham; Burns, Siobhan; Duckers, Gregor; Becker, Ruy Perez; von Bernuth, Horst; Latour, Sylvain; Faraci, Maura; Gattorno, Marco; Su, Helen C.; Pan-Hammarstroem, Qiang; Hammarstroem, Lennart; Lenardo, Michael J.; Ma, Cindy S.; Niehues, Tim; Aghamohammadi, Asghar; Rezaei, Nima; Ikinciogullari, Aydan; Tangye, Stuart G.; Lankester, Arjan C.; Boztug, Kaan
dc.date.accessioned2022-03-14T09:30:37Z
dc.date.available2022-03-14T09:30:37Z
dc.date.issued2020-12-03
dc.description.abstractBiallelic 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 EBV1 at diagnosis, but only similar to 30% 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 CD81 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.
dc.identifier.doi10.1182/blood.2020006738
dc.identifier.eissn1528-0020
dc.identifier.issn0006-4971
dc.identifier.pubmed32603431
dc.identifier.urihttps://hdl.handle.net/11424/243206
dc.identifier.wosWOS:000599645500010
dc.language.isoeng
dc.publisherAMER SOC HEMATOLOGY
dc.relation.ispartofBLOOD
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectEPSTEIN-BARR-VIRUS
dc.subjectSTEM-CELL TRANSPLANTATION
dc.subjectMEMORY B-CELLS
dc.subjectT-CELL
dc.subjectCOMBINED IMMUNODEFICIENCY
dc.subjectREFERENCE VALUES
dc.subjectEBV
dc.subjectGENERATION
dc.subjectIMMUNITY
dc.subjectCHILDREN
dc.titleExtended clinical and immunological phenotype and transplant outcome in CD27 and CD70 deficiency
dc.typearticle
dspace.entity.typePublication
local.avesis.id580d47d7-034f-4590-a10d-8da7832cf07b
local.import.packageSS16
local.indexed.atWOS
local.indexed.atPUBMED
local.journal.numberofpages18
local.journal.quartileQ1
oaire.citation.endPage2655
oaire.citation.issue23
oaire.citation.startPage2638
oaire.citation.titleBLOOD
oaire.citation.volume136
relation.isAuthorOfPublication3e9c297b-e636-4836-8f61-dc9c8b7c29cf
relation.isAuthorOfPublication.latestForDiscovery3e9c297b-e636-4836-8f61-dc9c8b7c29cf

Files

Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
Ghosh et al. - 2020 - Extended clinical and immunological phenotype and .pdf
Size:
1.37 MB
Format:
Adobe Portable Document Format
Download

Collections

Research Outputs