Limits...
A functional variant of PTPN22 confers risk for Vogt-Koyanagi-Harada syndrome but not for ankylosing spondylitis.

Zhang Q, Qi J, Hou S, Du L, Yu H, Cao Q, Zhou Y, Liao D, Kijlstra A, Yang P - PLoS ONE (2014)

Bottom Line: 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 (Pc = 0.009, Pc = 0.015 and Pc = 0.048 respectively).No significant association was observed concerning T cell activation and rs2488457 genotype.

View Article: PubMed Central - PubMed

Affiliation: The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology and Chongqing Eye Institute, Chongqing, P. R. China.

ABSTRACT

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 (PBonferroni correction (Pc) = 3.47×10(-7), OR = 1.54; Pc = 3.83×10(-8), OR = 1.40; Pc = 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 (Pc = 0.009, Pc = 0.015 and Pc = 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.

Show MeSH

Related in: MedlinePlus

The influence of rs2488457 on the activation of CD4+ T cells.(A) The frequency of CD4+CD44+CD69+ T cells from normal controls carrying different genotypes of rs2488457 (CC = 9, CG = 18, GG = 4). (B) The frequency of CD4+CD44+CD25+ T cells from normal controls carrying different genotypes of rs2488457 (CC = 9, CG = 18, GG = 4). Data are represented as the mean.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4016172&req=5

pone-0096943-g004: The influence of rs2488457 on the activation of CD4+ T cells.(A) The frequency of CD4+CD44+CD69+ T cells from normal controls carrying different genotypes of rs2488457 (CC = 9, CG = 18, GG = 4). (B) The frequency of CD4+CD44+CD25+ T cells from normal controls carrying different genotypes of rs2488457 (CC = 9, CG = 18, GG = 4). Data are represented as the mean.

Mentions: Previous studies showed that PTPN22 knockout mice accumulate activated T cells. To investigate the role of rs2488457 on T cell activation, we examined the early and late activation markers of CD4+ T cells in carriers of the different genotypes of rs2488457. PBMCs used for the detection of T cell activation were obtained from 31 unrelated genotyped healthy individuals (CC = 9, CG = 18, GG = 4). No significant association was observed concerning the frequencies of CD4+CD44+CD69+ and CD4+CD44+CD25+ T cells in the different genotypes of rs2488457 (Figure 4).


A functional variant of PTPN22 confers risk for Vogt-Koyanagi-Harada syndrome but not for ankylosing spondylitis.

Zhang Q, Qi J, Hou S, Du L, Yu H, Cao Q, Zhou Y, Liao D, Kijlstra A, Yang P - PLoS ONE (2014)

The influence of rs2488457 on the activation of CD4+ T cells.(A) The frequency of CD4+CD44+CD69+ T cells from normal controls carrying different genotypes of rs2488457 (CC = 9, CG = 18, GG = 4). (B) The frequency of CD4+CD44+CD25+ T cells from normal controls carrying different genotypes of rs2488457 (CC = 9, CG = 18, GG = 4). Data are represented as the mean.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4016172&req=5

pone-0096943-g004: The influence of rs2488457 on the activation of CD4+ T cells.(A) The frequency of CD4+CD44+CD69+ T cells from normal controls carrying different genotypes of rs2488457 (CC = 9, CG = 18, GG = 4). (B) The frequency of CD4+CD44+CD25+ T cells from normal controls carrying different genotypes of rs2488457 (CC = 9, CG = 18, GG = 4). Data are represented as the mean.
Mentions: Previous studies showed that PTPN22 knockout mice accumulate activated T cells. To investigate the role of rs2488457 on T cell activation, we examined the early and late activation markers of CD4+ T cells in carriers of the different genotypes of rs2488457. PBMCs used for the detection of T cell activation were obtained from 31 unrelated genotyped healthy individuals (CC = 9, CG = 18, GG = 4). No significant association was observed concerning the frequencies of CD4+CD44+CD69+ and CD4+CD44+CD25+ T cells in the different genotypes of rs2488457 (Figure 4).

Bottom Line: 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 (Pc = 0.009, Pc = 0.015 and Pc = 0.048 respectively).No significant association was observed concerning T cell activation and rs2488457 genotype.

View Article: PubMed Central - PubMed

Affiliation: The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology and Chongqing Eye Institute, Chongqing, P. R. China.

ABSTRACT

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 (PBonferroni correction (Pc) = 3.47×10(-7), OR = 1.54; Pc = 3.83×10(-8), OR = 1.40; Pc = 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 (Pc = 0.009, Pc = 0.015 and Pc = 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.

Show MeSH
Related in: MedlinePlus