Laboratory of Autoimmunity, The Medical College of Xiamen University, Xiamen University, Xiamen, China.
Genes Immun. 2012 Dec;13(8):641-52. doi: 10.1038/gene.2012.46. Epub 2012 Oct 18.
Protein tyrosine phosphatase non-receptor type 22 (PTPN22) is a strong susceptibility gene shared by many autoimmune diseases. The aim of this study was to explore the mechanisms underlying this relationship. We performed a comprehensive analysis of the association between PTPN22 polymorphism C1858T and autoimmune diseases. The results showed a remarkable pattern; PTPN22 C1858T was strongly associated with type I diabetes, rheumatoid arthritis, immune thrombocytopenia, generalized vitiligo with concomitant autoimmune diseases, idiopathic inflammatory myopathies, Graves' disease, juvenile idiopathic arthritis, myasthenia gravis, systemic lupus erythematosus, anti-neutrophil cytoplasmic antibody-associated vasculitis and Addison's disease. By contrast, PTPN22 C1858T showed a negligible association with systemic sclerosis, celiac disease, multiple sclerosis, psoriasis, ankylosing spondylitis, pemphigus vulgaris, ulcerative colitis, primary sclerosing cholangitis, primary biliary cirrhosis, Crohn's disease and acute anterior uveitis. Further analysis revealed a clear distinction between the two groups of diseases with regard to their targeted tissues: most autoimmune diseases showing an insignificant association with PTPN22 C1858T manifest in skin, the gastrointestinal tract or in immune privileged sites. These results showed that the association of PTPN22 polymorphism with autoimmune diseases depends on the localization of the affected tissue, suggesting a role of targeted organ variation in the disease manifestations.
蛋白酪氨酸磷酸酶非受体型 22（PTPN22）是许多自身免疫性疾病共同的强易感基因。本研究旨在探讨这种关系的机制。我们对 PTPN22 多态性 C1858T 与自身免疫性疾病的相关性进行了全面分析。结果显示出显著的模式；PTPN22 C1858T 与 1 型糖尿病、类风湿关节炎、免疫性血小板减少症、伴有自身免疫性疾病的全身性白癜风、特发性炎症性肌病、格雷夫斯病、幼年特发性关节炎、重症肌无力、系统性红斑狼疮、抗中性粒细胞胞质抗体相关性血管炎和艾迪生病强烈相关。相比之下，PTPN22 C1858T 与系统性硬化症、乳糜泻、多发性硬化症、银屑病、强直性脊柱炎、寻常性天疱疮、溃疡性结肠炎、原发性硬化性胆管炎、原发性胆汁性肝硬化、克罗恩病和急性前葡萄膜炎的相关性可忽略不计。进一步分析显示，两组疾病在靶向组织方面存在明显区别：大多数与 PTPN22 C1858T 相关性不强的自身免疫性疾病表现为皮肤、胃肠道或免疫特权部位的疾病。这些结果表明，PTPN22 多态性与自身免疫性疾病的相关性取决于受累组织的定位，提示靶向器官变化在疾病表现中起作用。
