کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
3351541 1216432 2012 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
The -346T polymorphism of the SH2D1A gene is a risk factor for development of autoimmunity/lymphoproliferation in males with defective Fas function
کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری ایمنی شناسی و میکروب شناسی ایمونولوژی
پیش نمایش صفحه اول مقاله
The -346T polymorphism of the SH2D1A gene is a risk factor for development of autoimmunity/lymphoproliferation in males with defective Fas function
چکیده انگلیسی

Inherited defects decreasing function of the Fas death receptor cause autoimmune lymphoproliferative syndrome (ALPS) and its variant Dianzani autoimmune lymphoproliferative disease (DALD). Since a deleterious mutation of the SH2D1A gene protects MRLlpr/lpr mice from ALPS development, we investigated the role of SH2D1A, located in the X chromosome, in 51 patients with ALPS or DALD by mutational screening of coding and regulative sequences. Allelic frequency of the -346C>T polymorphism was different in male patients and controls (-346T: 61% vs 36%, p = 0.01), with similar frequencies in ALPS and DALD. By contrast, no differences were found among females or between the controls and patients with multiple sclerosis (229 males, 157 females). Further analyses showed that -346C was a methylation site in CD8+ T and natural killer cells, and SH2D1A expression was higher in -346T than in -346C males. Finally, in vitro–activated T cells from -346T males produced lower amounts of interferon-γ than those from -346C males. These data suggest that -346T is a predisposing factor for ALPS and DALD in males possibly because of its effect on SAP expression influencing the T-cell response.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Human Immunology - Volume 73, Issue 5, May 2012, Pages 585–592
نویسندگان
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