Ghosh, S;
Köstel Bal, S;
Edwards, ESJ;
Pillay, B;
Jimenez-Heredia, R;
Rao, G;
Erol Cipe, F;
... Boztug, K; + view all
(2020)
Extended clinical and immunological phenotype and transplant outcome in CD27 and CD70 deficiency.
Blood
, 136
(23)
pp. 2638-2655.
10.1182/blood.2020006738.
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Morris_Extended clinical and immunological phenotype and transplant outcome in CD27 and CD70 deficiency_AAM.pdf - Accepted Version Download (2MB) | Preview |
Abstract
Biallelic mutations in the genes encoding CD27 or its ligand CD70 underlie inborn errors of immunity characterized predominantly by 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 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 (90%) of patients were EBV+ at diagnosis, but only ~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 (43%) patients 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.
| Type: | Article |
|---|---|
| Title: | Extended clinical and immunological phenotype and transplant outcome in CD27 and CD70 deficiency |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1182/blood.2020006738 |
| Publisher version: | https://doi.org/10.1182/blood.2020006738 |
| Language: | English |
| Additional information: | antigens, cd27, transplantation, infectious mononucleosis, lymphoma, hematopoietic stem cell transplantation, cancer, phenotype, signs and symptoms, allogeneic hematopoietic stem cell transplant, arthritis |
| Keywords: | antigens, cd27, transplantation, infectious mononucleosis, lymphoma, hematopoietic stem cell transplantation, cancer, phenotype, signs and symptoms, allogeneic hematopoietic stem cell transplant, arthritis |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10106268 |
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