title: Analysis of Class II human leucocyte antigens in Italian and Spanish systemic sclerosis.
abstract: 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.
authors.affiliation: Referral Center for Systemic Autoimmune Diseases, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico and University of Milan, Via Pace 9, 20122 Milan, Italy. lorberimm@hotmail.com
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Beretta
authors.forename: Blanca
authors.initials: B
authors.lastname: Rueda
authors.forename: Maurizio
authors.initials: M
authors.lastname: Marchini
authors.forename: Alessandro
authors.initials: A
authors.lastname: Santaniello
authors.forename: Carmen P
authors.initials: CP
authors.lastname: Simeón
authors.forename: Vicente
authors.initials: V
authors.lastname: Fonollosa
authors.forename: Monica
authors.initials: M
authors.lastname: Caronni
authors.forename: Raquel
authors.initials: R
authors.lastname: Rios-Fernandez
authors.forename: Patricia
authors.initials: P
authors.lastname: Carreira
authors.forename: Luis
authors.initials: L
authors.lastname: Rodriguez-Rodriguez
authors.forename: Antonia
authors.initials: A
authors.lastname: Moreno
authors.forename: Miguel A
authors.initials: MA
authors.lastname: López-Nevot
authors.forename: Ana
authors.initials: A
authors.lastname: Escalera
authors.forename: Maria F
authors.initials: MF
authors.lastname: González-Escribano
authors.forename: Javier
authors.initials: J
authors.lastname: Martin
authors.forename: Raffaella
authors.initials: R
authors.lastname: Scorza
mesh_terms: D001323:Autoantibodies / Q000032:analysis; D016022:Case-Control Studies; D020022:Genetic Predisposition to Disease; D006681:HLA-D Antigens / Q000235:genetics*; D059848:HLA-DQ alpha-Chains / Q000235:genetics; D059866:HLA-DQ beta-Chains / Q000235:genetics; D059811:HLA-DRB1 Chains / Q000235:genetics; D006650:Histocompatibility Testing / Q000379:methods; D006801:Humans; D007558:Italy / Q000453:epidemiology; D012595:Scleroderma, Systemic / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology; D013030:Spain / Q000453:epidemiology
chemical_list: D001323:Autoantibodies; D006681:HLA-D Antigens; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; C069050:HLA-DQA1 antigen; C069051:HLA-DQB1 antigen; D059811:HLA-DRB1 Chains
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