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

Alkhairy OK1
Perez-Becker R2
Driessen GJ3
Abolhassani H4
van Montfrans J5
Borte S6
Choo S7
Wang N8
Tesselaar K5
Fang M9
Bienemann K10
Boztug K11
Daneva A3
Mechinaud F12
Wiesel T13
Becker C14
Dückers G2
Siepermann K2
van Zelm MC15
Rezaei N16
van der Burg M15
Aghamohammadi A17
Seidel MG18
Niehues T19
Hammarström L20


The clinical and immunologic features of CD27 deficiency remain obscure because only a few patients have been identified to date.


We sought to identify novel mutations in TNFRSF7/CD27 and to provide an overview of clinicalimmunologic, and laboratory phenotypes in patients with CD27 deficiency.


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.


In addition to the previously reported homozygous mutations c.G24A/p.W8X (n = 2) and c.G158A/p.C53Y (n = 8), 4 novel mutationswere 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.


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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