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

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:129

Article

van Montfrans, Joris M.^1,2  Hoepelman, Andy I. M.³  Otto, Sigrid⁴  van Gijn, Marielle⁴  van de Corput, Lisette⁵  de Weger, Roel A.⁶  Monaco-Shawver, Linda⁷  Banerjee, Pinaki P.⁷  Sanders, Elisabeth A. M.^1,2  Jol-van der Zijde, Cornelia M.⁸  Betts, Michael R.⁹  Orange, Jordan S.⁷  Bloem, Andries C.⁵  Tesselaar, Kiki⁵ 

[1] Univ Med Ctr Utrecht, Dept Pediat Immunol, Wilhelmina Childrens Hosp, Utrecht, Netherlands

[2] Univ Med Ctr Utrecht, Dept Infect Dis, Wilhelmina Childrens Hosp, Utrecht, Netherlands

[3] Univ Med Ctr Utrecht, Dept Internal Med & Infect Dis, Utrecht, Netherlands

[4] Univ Med Ctr Utrecht, Dept Med Genet, Utrecht, Netherlands

[5] Univ Med Ctr Utrecht, Dept Immunol, Utrecht, Netherlands

[6] Univ Med Ctr Utrecht, Dept Pathol, Utrecht, Netherlands

[7] Childrens Hosp Philadelphia, Res Inst, Philadelphia, PA USA

[8] Leiden Univ, Dept Pediat, Med Ctr, NL-2300 RA Leiden, Netherlands

[9] Univ Penn, Dept Microbiol, Philadelphia, PA 19104 USA

关键词: EBV;    viremia;    hypogammaglobulinemia;    CD27;    immunodeficiency;    T cell;    B cell;    natural killer cell;    phenotype;   

DOI  :  10.1016/j.jaci.2011.11.013

来源: Elsevier

【 摘 要 】

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. (J Allergy Clin Immunol 2012;129:787-93.)

【 授权许可】

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