Extended clinical and immunological phenotype and transplant outcome in CD27 and CD70 deficiency
| العنوان: | Extended clinical and immunological phenotype and transplant outcome in CD27 and CD70 deficiency |
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| المؤلفون: | Emily S.J. Edwards, Safa Baris, Asghar Aghamohammadi, Hubert Kogler, Emma Gostick, Baran Erman, Geetha Rao, Ekrem Unal, Musa Karakukcu, Funda Erol Cipe, Kaan Boztug, Michael Paulussen, Sule Haskologlu, Sevgi Köstel Bal, Renate Krüger, Bénédicte Neven, David Price, Ruy Perez Becker, Joris M. van Montfrans, Stuart G. Tangye, Sylvain Latour, Tim Niehues, Elif Karakoc-Aydiner, Maura Faraci, Fabian Hauck, Dagmar Berghuis, Elisabeth Salzer, Roland Meisel, Theresa Cole, Yu Zhang, Arjan C. Lankester, Raúl Jiménez Heredia, Austen Worth, Ayse Metin, Emma C. Morris, Tooba Momen, Lennart Hammarström, Bethany Pillay, Claudia Gonzaga-Jauregui, Figen Dogu, Andy I. M. Hoepelman, Ebru Yilmaz, Cindy S. Ma, Sharon Choo, Horst von Bernuth, Ahmet Ozen, Dirk Holzinger, Helen C. Su, Nima Rezaei, Pieter L. A. Fraaij, Samaneh Zoghi, Andrew J. Oler, Aditya Gupta, Candan Islamoglu, Marco Gattorno, Sujal Ghosh, Leo Kager, Ebmt, Prasad T. Oommen, Aydan Ikinciogullari, Gregor Dückers, Inci Ilhan, Michael J. Lenardo, Hassan Abolhassani, Serdar Ceylaner, Qiang Pan-Hammarström, Siobhan O. Burns, Kubra Baskin, E. Graham Davies |
| المساهمون: | Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Pediatrics, Virology, Ghosh, 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, İstinye Üniversitesi, Tıp Fakültesi, Dahili Tıp Bilimleri Bölümü, Erol Cipe, Funda |
| المصدر: | Blood Blood, American Society of Hematology, 2020, 136 (23), pp.2638-2655. ⟨10.1182/blood.2020006738⟩ Blood, 136(23), 2638-2655. American Society of Hematology Blood, 136(23), 2638-2655. AMER SOC HEMATOLOGY |
| مصطلحات موضوعية: | Male, Mononucleosis, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Medizin, CHILDREN, Hematopoietic stem cell transplantation, T-CELL, medicine.disease_cause, Biochemistry, 0302 clinical medicine, immune system diseases, hemic and lymphatic diseases, MEMORY B-CELLS, EPSTEIN-BARR-VIRUS, Child, 0303 health sciences, Hematology, Hematopoietic Stem Cell Transplantation, Allografts, 3. Good health, Survival Rate, 030220 oncology & carcinogenesis, Child, Preschool, Female, Adult, medicine.medical_specialty, Adolescent, Immunology, chemical and pharmacologic phenomena, IMMUNITY, Disease-Free Survival, 03 medical and health sciences, Immune system, EBV, Internal medicine, medicine, Humans, 030304 developmental biology, Retrospective Studies, Hemophagocytic lymphohistiocytosis, business.industry, Genetic Diseases, Inborn, Immunologic Deficiency Syndromes, Infant, STEM-CELL TRANSPLANTATION, Cell Biology, Immune dysregulation, COMBINED IMMUNODEFICIENCY, medicine.disease, REFERENCE VALUES, Lymphoma, Tumor Necrosis Factor Receptor Superfamily, Member 7, business, CD8, GENERATION, CD27 Ligand |
| الوصف: | 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 ∼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 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. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1528-0020 0006-4971 |
| DOI: | 10.1182/blood.2020006738 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b3b38b201b619a092e6fa61f30bc2995Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....b3b38b201b619a092e6fa61f30bc2995 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15280020 00064971 |
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| DOI: | 10.1182/blood.2020006738 |