A Functional Variant of PTPN22 Confers Risk for Vogt-Koyanagi-Harada Syndrome but Not for Ankylosing Spondylitis

BACKGROUND: Protein tyrosine phosphatase non-receptor 22 (PTPN22) is a key negative regulator of T lymphocytes and has emerged as an important candidate susceptibility factor for a number of immune-related diseases. This study aimed to examine the predisposition of PTPN22 SNPs to Vogt-Koyanagi-Harada (VKH) syndrome and acute anterior uveitis (AAU) associated with ankylosing spondylitis (AS). METHODS: A total of 1005 VKH syndrome, 302 AAU(+)AS(+) patients and 2010 normal controls among the Chinese Han population were enrolled in the study. Genotyping, PTPN22 expression, cell proliferation, cytokine production and cell activation were examined by PCR-RFLP, Real-time PCR, CCK8, ELISA and Flow cytometry. RESULTS: The results showed significantly increased frequencies of the rs2488457 CC genotype and C allele but a decreased frequency of the GG genotype in VKH syndrome patients (P(Bonferroni correction) (P(c)) = 3.47×10(−7), OR = 1.54; P(c) = 3.83×10(−8), OR = 1.40; P(c) = 6.35×10(−4), OR = 0.62; respectively). No significant association of the tested SNPs with AAU(+)AS(+) patients was observed. Functional studies showed a decreased PTPN22 expression, impaired cell proliferation and lower production of IL-10 in rs2488457 CC cases compared to GG cases (P(c) = 0.009, P(c) = 0.015 and P(c) = 0.048 respectively). No significant association was observed concerning T cell activation and rs2488457 genotype. CONCLUSIONS: The study showed that a functional variant of PTPN22 confers risk for VKH syndrome but not for AAU(+)AS(+) in a Chinese Han population, which may be due to a modulation of the PTPN22 expression, PBMC proliferation and IL-10 production.