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      Chronic periaortitis and HLA-DRB1*03: another clue to an autoimmune origin.

      Arthritis and Rheumatism
      Adolescent, Adult, Aged, Autoimmune Diseases, genetics, immunology, Child, Cohort Studies, Female, Genetic Predisposition to Disease, Genotype, HLA-A Antigens, HLA-B Antigens, HLA-DR Antigens, HLA-DRB1 Chains, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide, Retroperitoneal Fibrosis

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          Abstract

          Patients with chronic periaortitis (CP) often show clinical and laboratory findings of a systemic autoimmune disorder. The aim of the present study was to investigate the role of the HLA system in CP. Low-resolution genotyping for HLA-A, HLA-B, and HLA-DRB1 loci and genotyping of TNFA(-238)A/G and TNFA(-308)A/G single nucleotide polymorphisms were performed in 35 consecutive patients with CP and 350 healthy controls. The HLA-DRB1*03 allele frequency was strikingly higher in patients with CP than in controls (24.28% versus 9.14%; chi(2) = 15.50, P = 0.000084, corrected P [P(corr)] = 0.0012, odds ratio [OR] 3.187, 95% confidence interval [95% CI] 1.74-5.83); the HLA-B*08 allele frequency was also higher in patients than in controls (17.14% versus 6.28%; chi(2)=11.12, P = 0.0008, P(corr) = 0.0269, OR 3.085, 95% CI 1.54-6.16). The A*01 allele frequency was significantly different (P = 0.0463), but the statistical significance was lost after correction for multiple testing (P(corr) = 0.5088). TNFA(-238)A allele and TNFA(-308)A allele frequencies were not significantly different (P = 0.512 and P = 0.445, respectively). Comparison of the main clinical and laboratory findings suggestive of a systemic autoimmune disease (e.g., acute-phase reactants, constitutional symptoms, other autoimmune diseases associated with CP) between the HLA-DRB1*03-positive and the HLA-DRB1*03-negative patients showed that the former group had significantly higher levels of C-reactive protein (P = 0.045) at disease onset, although this difference was not statistically significant after correction for multiple tests (P(corr) = 0.369). The HLA system plays a role in susceptibility to CP. The strong association between CP and HLA-DRB1*03, an allele linked to a wide range of autoimmune conditions, further supports the view that CP may represent a clinical manifestation of an autoimmune disease.

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