Novel mutations in TNFRSF7/CD27: Clinical, immunologic, and genetic characterization of human CD27 deficiency

Omar K. Alkhairy, Ruy Perez-Becker, Gertjan J. Driessen, Hassan Abolhassani, Joris Van Montfrans, Stephan Borte, Sharon Choo, Ning Wang, Kiki Tesselaar, Mingyan Fang, Kirsten Bienemann, Kaan Boztug, Ana Daneva, Francoise Mechinaud, Thomas Wiesel, Christian Becker, Gregor Dückers, Kathrin Siepermann, Menno C. Van Zelm, Nima RezaeiMirjam Van Der Burg, Asghar Aghamohammadi, Markus G. Seidel, Tim Niehues, Lennart Hammarström

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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.

Original languageEnglish
Pages (from-to)703-712.e10
Number of pages20
JournalJournal of Allergy and Clinical Immunology
Issue number3
Publication statusPublished - 1 Sep 2015
Externally publishedYes


  • CD27 deficiency
  • EBV-induced lymphoproliferation
  • hemophagocytic lymphohistiocytosis
  • Hodgkin lymphoma
  • hypogammaglobulinemia

Cite this

Alkhairy, O. K., Perez-Becker, R., Driessen, G. J., Abolhassani, H., Van Montfrans, J., Borte, S., Choo, S., Wang, N., Tesselaar, K., Fang, M., Bienemann, K., Boztug, K., Daneva, A., Mechinaud, F., Wiesel, T., Becker, C., Dückers, G., Siepermann, K., Van Zelm, M. C., ... Hammarström, L. (2015). Novel mutations in TNFRSF7/CD27: Clinical, immunologic, and genetic characterization of human CD27 deficiency. Journal of Allergy and Clinical Immunology, 136(3), 703-712.e10.