Analysis of class II human leucocyte antigens in Italian and Spanish systemic sclerosis

Lorenzo Beretta, Blanca Rueda, Maurizio Marchini, Alessandro Santaniello, Carmen P. Simeón, Vicente Fonollosa, Monica Caronni, Raquel Rios-fernandez, Patricia Carreira, Luis Rodriguez-rodriguez, Antonia Moreno, Miguel A. López-nevot, Ana Escalera, Maria F. González-escribano, Javier Martin, Raffaella Scorza

Research output: Contribution to journalArticlepeer-review


Objective: To determine the role of Class II HLAs in SSc patients from Italy and Spain and in SSc patients of Caucasian ancestry. Methods: Nine hundred and forty-four SSc patients (Italy 392 patients; Spain 452 patients) and 1320 ethnically matched healthy controls (Italy 398 patients; Spain 922 patients) were genotyped up to the fourth digit by PCR with sequence-specific oligonucleotides for HLA-DRB1, DQA1 and DQB1 loci. Patients included 390 ACA-positive and 254 anti-topo I-positive subjects. Associations between SSc or SSc-specific antibodies and HLA alleles or HLA haplotypes were sought via the chi-square test after 10 000-fold permutation testing. A meta-analysis including this study cohort and other Caucasoids samples was also conducted. Results: In both the cohorts, the strongest association was observed between the HLA-DRB1*1104 allele and SSc or anti-topo I antibodies. The HLA-DRB1*1104 -DQA1*0501 -DQB1*0301 haplotype was overrepresented in Italian [odds ratio (OR) = 2.069, 95% asymptotic CIs (CI 95) 1.486, 2.881; P <0.001] and in Spanish patients (OR = 6.707, CI 95 3.974, 11.319; P <0.001) as well as in anti-topo-positive patients: Italy (OR = 2.642, CI 95 1.78, 3.924; P <0.001) and Spain (OR = 20.625, CI 95 11.536, 36.876; P <0.001). In both the populations we also identified an additional risk allele (HLA-DQB1*03) and a protective allele (HLA-DQB1*0501) in anti-topo-positive patients. The meta-analysis showed different statistically significant associations, the most interesting being the differential association between HLA-DRB1*01 alleles and ACAs (OR = 1.724, CI 95 1.482, 2.005; P <0.001) or topo I antibodies (OR = 0.5, CI 95 0.384, 0.651; P <0.001). Conclusions: We describe multiple robust associations between SSc and HLA Class II antigens in Caucasoids that may help to understand the genetic architecture of SSc.

Original languageEnglish
Article numberker335
Pages (from-to)52-59
Number of pages8
Issue number1
Publication statusPublished - Jan 2012


  • Epidemiology
  • Genetics
  • HLA
  • Systemic sclerosis

ASJC Scopus subject areas

  • Rheumatology
  • Pharmacology (medical)


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