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PTPN22 R620W polymorphism and ANCA disease risk in white populations: a metaanalysis.

ABSTRACT: No clear consensus has been reached on the PTPN22 R620W polymorphism and anti-neutrophil cytoplasmic antibody (ANCA) disease, especially when stratified by ANCA specificity and disease phenotypes.A metaanalysis was conducted on the PTPN22 R620W polymorphism across 4 studies in 1399 white patients with ANCA disease and 9934 normal control subjects.Overall, metaanalysis showed a statistically significant association between the A allele and ANCA disease in all subjects (OR 1.44, 95% CI 1.26-1.64, p < 0.00001), and stratification by disease category indicated the A allele was associated with granulomatosis with polyangiitis (Wegener's; GPA; OR 1.72, 95% CI 1.35-2.20, p < 0.0001) and microscopic polyangiitis (MPA; OR 1.53, 95% CI 1.08-2.15, p = 0.02) as compared to controls. However, when stratified by ANCA specificity, the association of the A allele was statistically evident among those with proteinase 3 (PR3) ANCA disease (OR 1.74, 95% CI 1.25-2.430, p = 0.001), with the same trend but not statistically associated with myeloperoxidase ANCA disease (OR 1.94, 95% CI 0.64-5.85, p = 0.24). The marked associations were also demonstrated between this allele with lung (OR 1.69, 95% CI 1.21-2.36, p = 0.002), ENT (OR 2.03, 95% CI 1.45-2.84, p < 0.0001), skin (OR 2.55, 95% CI 1.69-3.84, p < 0.0001), and peripheral neuropathy involvement (OR 2.12, 95% CI 1.39-3.22, p = 0.0005).The PTPN22 620W allele confers susceptibility to the occurrence and development of ANCA disease in whites, with specific evidence among subsets with GPA, MPA, and PR3 ANCA.

SUBMITTER: Cao Y

PROVIDER: S-EPMC4314360 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature

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PTPN22 R620W polymorphism and ANCA disease risk in white populations: a metaanalysis.

Cao Yali Y Liu Kuo K Tian Zhigang Z Hogan Susan L SL Yang Jiajin J Poulton Caroline J CJ Falk Ronald J RJ Li Wenge W

The Journal of rheumatology 20141201 2

<h4>Objective</h4>No clear consensus has been reached on the PTPN22 R620W polymorphism and anti-neutrophil cytoplasmic antibody (ANCA) disease, especially when stratified by ANCA specificity and disease phenotypes.<h4>Methods</h4>A metaanalysis was conducted on the PTPN22 R620W polymorphism across 4 studies in 1399 white patients with ANCA disease and 9934 normal control subjects.<h4>Results</h4>Overall, metaanalysis showed a statistically significant association between the A allele and ANCA di ...[more]

PMID: 25448792

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Project description:ObjectivesInfluenza infection is a significant cause of respiratory morbidity among pregnant women. Seasonal influenza vaccination engages innate immune receptors to promote protective immunity. A coding polymorphism (R620W) in PTPN22 imparts elevated risk for human infection and autoimmune disease, predisposes to diminished innate immune responses, and associates with reduced immunization responses. We sought to quantify the effects of PTPN22-R620W on humoral and cell-mediated immune responses to the inactivated influenza vaccine among healthy pregnant women.Study designImmune responses were measured in healthy pregnant R620W carrier (n = 17) and non-carrier (n = 33) women receiving the 2013 quadrivalent inactivated influenza vaccine (Fluzone). Hemagglutination inhibition assays were performed to quantify neutralizing antibodies; functional influenza-reactive CD4 T cells were quantified by flow cytometry, and influenza-specific CD8 T cells were enumerated with MHC Class I tetramers. Antibody seroconversion data were evaluated by Chi-square analysis, and the Mann-Whitney or Wilcoxon signed-rank tests were applied to T cell response data.ResultsPTPN22 R620W carrier (n = 17) and non-carrier (n = 33) groups did not differ in age, parity, BMI, gestational age at time of vaccine, or history of prior influenza vaccination. After Fluzone exposure, 51.5% of non-carriers met criteria for antibody seroconversion to H1N1 influenza, compared with 23.5% of R620W carriers (p = 0.06). Influenza-reactive CD4 T cells showed modest increase at days 9-15 after vaccination in both R620W carriers and non-carriers (p = 0.02 and p = 0.04, respectively). However, there was no difference in overall response between the two groups (p = 0.6). The vaccine did not result in significant induction of influenza-specific CD8 T cells in either group.ConclusionsThere was no significant difference among healthy pregnant R620W carriers and non-carriers in H1N1 antibody seroconversion rates after influenza vaccination. Studies of larger cohorts will be needed to define the effect of PTPN22 risk allele carriage on antibody and T cell responses to influenza vaccination during pregnancy.

Dataset Information

PTPN22 R620W polymorphism and ANCA disease risk in white populations: a metaanalysis.

Publications

PTPN22 R620W polymorphism and ANCA disease risk in white populations: a metaanalysis.

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