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

作者：Beretta Lorenzo^*; Rueda Blanca; Marchini Maurizio; Santaniello Alessandro; Simeon Carmen P; Fonollosa Vicente; Caronni Monica; Rios Fernandez Raquel; Carreira Patricia; Rodriguez Rodriguez Luis; Moreno Antonia; Lopez Nevot Miguel A; Escalera Ana; Gonzalez Escribano Maria F; Martin Javier; Scorza Raffaella

来源：Rheumatology, 2012, 51(1): 52-59.

DOI：10.1093/rheumatology/ker335

• systemic sclerosis
• HLA
• genetics
• epidemiology

Objective. To determine the role of Class II HLAs in SSc patients from Italy and Spain and in SSc patients of Caucasian ancestry. %26lt;br%26gt;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. %26lt;br%26gt;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 over-represented in Italian [odds ratio (OR) = 2.069, 95% asymptotic CIs (CI(95)) 1.486, 2.881; P%26lt;0.001] and in Spanish patients (OR = 6.707, CI(95) 3.974, 11.319; P%26lt;0.001) as well as in anti-topo-positive patients: Italy (OR = 2.642, CI(95) 1.78, 3.924; P%26lt;0.001) and Spain (OR = 20.625, CI(95) 11.536, 36.876; P%26lt;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%26lt;0.001) or topo I antibodies (OR = 0.5, CI(95) 0.384, 0.651; P%26lt;0.001). %26lt;br%26gt;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.

• 出版日期2012-1