Jagiello Peter, Aries Peer, Arning Larissa, Wagenleiter Sonja E N, Csernok Elena, Hellmich Bernhard, Gross Wolfgang L, Epplen Joerg T
Ruhr University, Bochum, Germany.
Arthritis Rheum. 2005 Dec;52(12):4039-43. doi: 10.1002/art.21487.
Analyses of families with multiple autoimmune disorders have revealed a functional polymorphism, 620W, in the intracellular tyrosine phosphatase gene PTPN22 as a predisposing factor for type 1 diabetes, seropositive rheumatoid arthritis, systemic lupus erythematosus, and Hashimoto thyroiditis, and the presence of the PTPN22 protein appears to herald the development of autoantibodies in these disorders. This study therefore examined whether the functionally relevant PTPN22 polymorphism is associated with Wegener's granulomatosis (WG).
A population-based study was performed for the PTPN22 polymorphism in 199 patients with WG and in 399 healthy individuals. The R620W variation was investigated by simple restriction fragment-length polymorphism analysis.
The PTPN22 620W allele frequency was significantly increased in antineutrophil cytoplasmic antibody (ANCA)-positive WG patients compared with healthy controls (P < 0.001). The association was particularly striking in patients with kidney, lung, eye, and peripheral nervous system involvement (i.e., those with generalized WG).
The PTPN22 620W allele appears to be involved in the pathogenesis of WG, and ANCA positivity seems to be the hallmark.
对患有多种自身免疫性疾病的家族进行分析后发现，细胞内酪氨酸磷酸酶基因PTPN22中存在一种功能性多态性620W，它是1型糖尿病、血清学阳性类风湿性关节炎、系统性红斑狼疮和桥本甲状腺炎的易感因素，并且PTPN22蛋白的存在似乎预示着这些疾病中自身抗体的产生。因此，本研究检测了功能相关的PTPN22多态性是否与韦格纳肉芽肿病（WG）相关。
对199例WG患者和399名健康个体进行了PTPN22多态性的基于人群的研究。通过简单的限制性片段长度多态性分析研究R620W变异。
与健康对照相比，抗中性粒细胞胞浆抗体（ANCA）阳性的WG患者中PTPN22 620W等位基因频率显著增加（P < 0.001）。这种关联在有肾脏、肺、眼和周围神经系统受累的患者（即全身性WG患者）中尤为显著。
PTPN22 620W等位基因似乎参与了WG的发病机制，而ANCA阳性似乎是其标志。
