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Polymorphism of immunoglobulin (Ig) enhancer element HS1,2A: allele *2 associates with Systemic Sclerosis. Comparison with HLA-DR and DQ alleles frequency.
  1. D Frezza
  1. Department of Biology, Italy
    1. V Giambra
    1. Department of Biology, Italy
      1. B Tolusso
      1. Division of Rheumatology-School of Medicine, Catholic University of Sacred Heart, Rome, Italy
        1. M De Santis
        1. Division of Rheumatology-School of Medicine, Catholic University of Sacred Heart, Rome, Italy
          1. S Bosello
          1. Division of Rheumatology-School of Medicine, Catholic University of Sacred Heart, Rome, Italy
            1. S Vettori
            1. Division Of Rheumatology, II University of Naples, Naples, Italy
              1. G Triolo
              1. Rheumatology Unit, University of Palermo, Palermo, Italy
                1. G Valentini
                1. Division Of Rheumatology, II University of Naples, Naples, Italy
                  1. G Ferraccioli (gf.ferraccioli{at}rm.unicatt.it)
                  1. Division of Rheumatology-School of Medicine, Catholic University of Sacred Heart, Rome, Italy

                    Abstract

                    Objective: To investigate the relationship of the polymorphic enhancer HS1,2 central to the 3¡¯ enhancer complex regulatory region (IgH3¡¯ EC) of the Ig heavy chain genes with Systemic sclerosis (SSc) disease and compare it to HLA-DR and DQ associations.

                    Methods: 116 SSc patients were classified as diffuse (dSSc) or limited SSc (lSSc), and as carriers of anti-topoisomerase I (anti-Scl70) or anti-centromere (ACA) antibodies. Allele and genotype frequencies were assessed in the population as a whole and in the two major subsets, dSSc and lSSc. The concentration of peripheral blood immunoglobulin levels was also determined and analyzed according to the genotypes.

                    Results: The analysis of genotypes for the four alleles of the HS1,2A enhancer showed an increased frequency of the allele *2 in the SSc cohort highly significant vs controls (57% vs 40%, p<0.0001). Considering the autoantibody pattern, we found that the frequency of the 2/2 genotype was increased in ACA+ patients (42%) and anti-Scl70+ patients (31%) compared to the control group (15%). The differences of allelic frequencies among dSSc vs lSSc or ACA+ vs anti-Scl70+ patients were not significant, although highly significant when comparing each sub-group to the control group. HLA-DRB1*11 and DQB1*03 associated with SSc. No association was seen between HS1,2A enhancer polymorphism and HLA alleles.

                    Conclusions: These data confirm the hypothesis of an increased risk of having SSc in carriers of the allele *2, suggesting an intriguing function of this polymorphism for the B cell regulation.

                    • HS1, 2 enhancer element
                    • Ig regulatory region
                    • polymorphism
                    • systemic sclerosis

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