Immune deficiencies, infection, and systemic immune disorders
CD27 deficiency is associated with combined immunodeficiency and persistent symptomatic EBV viremia

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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.

Section snippets

Methods

Evaluation of blood, bone marrow biopsy specimens, vaccination responses, and medical records were carried out after written informed consent was obtained in accordance with local medical ethics committee guidelines.

Patient identification and genetic diagnosis

Lymphocyte subset analysis was performed in a patient with a confirmed but unexplained diagnosis of CVID and persistent symptomatic EBV viremia. In this patient no CD27+ T or memory B cells were detected, despite the presence of normal percentages of naive (CD45RA+) T cells and switched IgG+ and IgA+ B cells (subpopulations normally expressing CD27). Immunohistochemistry (results not shown) and extended flow cytometric analysis with additional anti-CD27 mAbs and a recombinant ligand (CD70)

Discussion

We describe 2 cases of CD27 deficiency that presented with persistent symptomatic EBV viremia after primary infection with EBV at a young age. In the one case in which more detailed immunologic evaluation was possible, the immunologic phenotype shared similarities with that of CVID in that there was hypogammaglobulinemia and partially impaired specific antibody function. Overall, our findings demonstrate that CD27 deficiency might be associated with a distinct immunologic phenotype, one of

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    Supported by National Institutes of Health grants NIH AI-067946 (J.S.O.) and NIH RO1 AI076066 (M.R.B.).

    Disclosure of potential conflict of interest: J. S. Orange receives research support from the National Institutes of Health. The rest of the authors declare that they have no relevant conflicts of interest.

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