Novel mutations in TNFRSF7/CD27: Clinical, immunologic, and genetic characterization of human CD27 deficiency
Alkhairy, Omar K.; Perez-Becker, Ruy; Driessen, Gertjan J.; Abolhassani, Hassan; van Montfrans, JM; Borte, Stephan; Choo, Sharon; Wang, Ning; Tesselaar, Kiki; Fang, Mingyan; Bienemann, Kirsten; Boztug, Kaan; Daneva, Ana; Mechinaud, Francoise; Wiesel, Thomas; Becker, Christian; Duckers, Gregor; Siepermann, Kathrin; van Zelm, Menno C.; Rezaei, Nima; van der Burg, Mirjam; Aghamohammadi, Asghar; Seidel, Markus G.; Niehues, Tim; Hammarstrom, Lennart
(2015) Journal of Allergy and Clinical Immunology, volume 136, issue 3, pp. 703 - +
(Article)
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
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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 solubleCD27 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.
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Keywords: CD27 deficiency, EBV-induced lymphoproliferation, Hodgkin lymphoma, hypogammaglobulinemia, hemophagocytic lymphohistiocytosis, EPSTEIN-BARR-VIRUS, COMMON VARIABLE IMMUNODEFICIENCY, NATURAL-KILLER-CELLS, T-CELLS, LYMPHOPROLIFERATIVE DISORDER, CD27-CD70 INTERACTIONS, READ ALIGNMENT, EBV INFECTION, SCID MICE, NK CELLS, Journal Article, Research Support, Non-U.S. Gov't
ISSN: 0091-6749
Publisher: Mosby Inc.
(Peer reviewed)