CD27 deficiency is associated with combined immunodeficiency and persistent symptomatic EBV viremia

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• 作者：Joris M. van Montfrans ; MD ; PhD^a ; ^{j.vanmontfrans@umcutrecht.nl} ; Andy I.M. Hoepelman ; MD ; PhD^b ; Sigrid Otto ; BSc^c ; Marielle van Gijn ; PhD^c ; Lisette van de Corput ; PhD^d ; Roel A. de Weger ; PhD^e ; Linda Monaco-Shawver ; BSc^f ; Pinaki P. Banerjee ; PhD^f ; Elisabeth A.M. Sanders ; MD ; PhD^a ; Cornelia M. Jol– ; van der Zijde ; PhD^g ; Michael R. Betts ; PhD^h ; Jordan S. Orange ; MD ; PhD^f ; Andries C. Bloem ; PhD^d ; Kiki Tesselaar ; PhD^d
• 关键词：EBV ; viremia ; hypogammaglobulinemia ; CD27 ; immunodeficiency ; T cell ; B cell ; natural killer cell ; phenotype
• 刊名：Journal of Allergy and Clinical Immunology
• 出版年：2012
• 出版时间：March, 2012
• 年：2012
• 卷：129
• 期：3
• 页码：787-793.e6
• 全文大小：1372 K

文摘

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Background

CD27 is a lymphocyte costimulatory molecule that regulates T-cell, natural killer (NK) cell, B-cell, and plasma cell function, survival, and differentiation. On the basis of its function and expression pattern, we considered CD27 a candidate gene in patients with hypogammaglobulinemia.

Objective

We sought to describe the clinical and immunologic phenotypes of patients with genetic CD27 deficiency.

Methods

A molecular and extended immunologic analysis was performed on 2 patients lacking CD27 expression.

Results

We identified 2 brothers with a homozygous mutation in CD27 leading to absence of CD27 expression. Both patients had persistent symptomatic EBV viremia. The index patient was hypogammaglobulinemic, and immunoglobulin replacement therapy was initiated. His brother had aplastic anemia in the course of his EBV infection and died from fulminant gram-positive bacterial sepsis. Immunologically, lack of CD27 expression was associated with impaired T cell-dependent B-cell responses and T-cell dysfunction.

Conclusion

Our findings identify a role for CD27 in human subjects and suggest that this deficiency can explain particular cases of persistent symptomatic EBV viremia with hypogammaglobulinemia and impaired T cell-dependent antibody generation.