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Novel Mutations in Tnfrsf7/Cd27: Clinical, Immunologic, and Genetic Characterization of Human Cd27 Deficiency Publisher Pubmed



Alkhairy OK1, 2 ; Perezbecker R3 ; Driessen GJ5 ; Abolhassani H1, 6 ; Van Montfrans J8 ; Borte S1, 9 ; Choo S10 ; Wang N1 ; Tesselaar K8 ; Fang M11 ; Bienemann K12 ; Boztug K13 ; Daneva A5 ; Mechinaud F15 Show All Authors
Authors
  1. Alkhairy OK1, 2
  2. Perezbecker R3
  3. Driessen GJ5
  4. Abolhassani H1, 6
  5. Van Montfrans J8
  6. Borte S1, 9
  7. Choo S10
  8. Wang N1
  9. Tesselaar K8
  10. Fang M11
  11. Bienemann K12
  12. Boztug K13
  13. Daneva A5
  14. Mechinaud F15
  15. Wiesel T16
  16. Becker C4
  17. Duckers G3
  18. Siepermann K3
  19. Van Zelm MC17
  20. Rezaei N6, 7
  21. Van Der Burg M17
  22. Aghamohammadi A6
  23. Seidel MG14, 18
  24. Niehues T3
  25. Hammarstrom L1
Show Affiliations
Authors Affiliations
  1. 1. Division of Clinical Immunology, Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden
  2. 2. Department of Pathology and Laboratory Medicine, King Abdulaziz Medical City, Riyadh, Saudi Arabia
  3. 3. Centre for Child and Adolescent Health, HELIOS Clinic Krefeld, Krefeld, Germany
  4. 4. Institute for Hygiene and Laboratory Medicine, HELIOS Clinic Krefeld, Krefeld, Germany
  5. 5. Erasmus MC, Department of Pediatrics, Subdepartment of Pediatric Infectious Disease and Immunology, Rotterdam, Netherlands
  6. 6. Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran
  7. 7. Department of Immunology, School of Medicine, And Molecular Immunology Research Center, Tehran University of Medical Sciences, Tehran, Iran
  8. 8. Departments of Pediatric Immunology and Infectious Diseases, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, Netherlands
  9. 9. Translational Centre for Regenerative Medicine (TRM), University of Leipzig, Leipzig, Germany
  10. 10. Department of Allergy and Immunology, Royal Children's Hospital, Melbourne, Australia
  11. 11. BGI-Shenzhen, Beishan Industrial Zone, Yantian District, Shenzhen, China
  12. 12. Pediatric Oncology, Hematology and Clinical Immunology, Medical Faculty, Heinrich Heine University, Dusseldorf, Germany
  13. 13. CeMM Research Center of Molecular Medicine, Austrian Academy of Sciences, Division of Neonatal Medicine and Intensive Care, Department of Pediatrics and Adolescent Medicine, Medical University Vienna, Vienna, Austria
  14. 14. St Anna Children's Hospital, Division of Pediatric Hematology-Oncology, Department of Pediatrics and Adolescent Medicine, Medical University Vienna, Vienna, Austria
  15. 15. Children's Cancer Centre, Royal Children's Hospital, Melbourne, Australia
  16. 16. Children's Hospital, Vestische Youth Hospital, University of Witten/Herdecke, Datteln, Germany
  17. 17. Erasmus MC, Department of Immunology, Rotterdam, Netherlands
  18. 18. Division of Pediatric Hematology Oncology, Department of Pediatrics and Adolescent Medicine, Medical University of Graz, Graz, Austria

Source: Journal of Allergy and Clinical Immunology Published:2015


Abstract

Background The clinical and immunologic features of CD27 deficiency remain obscure because only a few patients have been identified to date. Objective We sought to identify novel mutations in TNFRSF7/CD27 and to provide an overview of clinical, immunologic, and laboratory phenotypes in patients with CD27 deficiency. Methods Review of the medical records and molecular, genetic, and flow cytometric analyses of the patients and family members were performed. Treatment outcomes of previously described patients were followed up. Results In addition to the previously reported homozygous mutations c.G24A/p.W8X (n = 2) and c.G158A/p.C53Y (n = 8), 4 novel mutations were identified: homozygous missense c.G287A/p.C96Y (n = 4), homozygous missense c.C232T/p.R78W (n = 1), heterozygous nonsense c.C30A/p.C10X (n = 1), and compound heterozygous c.C319T/p.R107C-c.G24A/p.W8X (n = 1). EBV-associated lymphoproliferative disease/hemophagocytic lymphohistiocytosis, Hodgkin lymphoma, uveitis, and recurrent infections were the predominant clinical features. Expression of cell-surface and soluble CD27 was significantly reduced in patients and heterozygous family members. Immunoglobulin substitution therapy was administered in 5 of the newly diagnosed cases. Conclusion CD27 deficiency is potentially fatal and should be excluded in all cases of severe EBV infections to minimize diagnostic delay. Flow cytometric immunophenotyping offers a reliable initial test for CD27 deficiency. Determining the precise role of CD27 in immunity against EBV might provide a framework for new therapeutic concepts. © 2015 American Academy of Allergy, Asthma & Immunology.
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