Article Text

Download PDFPDF
Polymorphism of immunoglobulin enhancer element HS1,2A: allele *2 associates with systemic sclerosis. Comparison with HLA-DR and DQ allele frequency
  1. D Frezza1,
  2. V Giambra1,
  3. B Tolusso4,
  4. M De Santis4,
  5. S Bosello4,
  6. S Vettori2,
  7. G Triolo3,
  8. G Valentini2,
  9. G Ferraccioli4
  1. 1Department of Biology “Enrico Calef”, University of Tor Vergata, Rome
  2. 2Division of Rheumatology, II University of Naples-Naples
  3. 3Rheumatology Unit-University of Palermo
  4. 4Division of Rheumatology, School of Medicine Catholic University of the Sacred Heart, Rome, Italy
  1. Correspondence to:
    D Frezza
    Associate Professor of Genetics, University of Tor Vergata; frezza{at}; to G F Ferraccioli, MD, Professor, Director Division of Rheumatology, UCSC- Catholic University of Rome, 00168 Rome, Italy; gf.ferraccioli{at}


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

Methods: A total of 116 patients with SSc were classified as diffuse (dSSc) or limited (lSSc), and as carriers of antitopoisomerase I (anti-Scl70) or anticentromere (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 analysed according to the genotypes.

Results: The analysis of genotypes for the four alleles of the HS1,2A enhancer showed an increased frequency of allele *2 in the SSc cohort highly significant versus 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 with the control group (15%). The differences of allelic frequencies among dSSc versus lSSc or ACA+ versus anti-Scl70+ patients were not significant, although highly significant when comparing each subgroup with 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 there was an increased risk of having SSc in carriers of allele *2, suggesting an intriguing function of this polymorphism for B-cell regulation.

  • CI, confidence interval
  • DLCO, diffusion capacity for carbon monoxide
  • FVC, forced vital capacity
  • HRCT, high resolution computed tomography
  • OR, odds ratio
  • PCR, polymerase chain reaction

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.


  • Published Online First 28 March 2007