HLA-DRB1, TAP2/TAP1, and HLA-DPB1 haplotypes in Finnish juvenile idiopathic arthritis: more complexity within the MHC

Abstract

This study further defines genetic susceptibility to JIA in the region centromeric to HLA-DRB1. DNA from 234 Finnish JIA nuclear families and 639 elderly Finnish control individuals was genotyped for five functional SNPs within the TAP2 and TAP1 loci (B200 kb centromeric of HLA-DRB1). Subsets of the controls (186) and patients (145) that had been previously typed for HLA-DRB1 were also genotyped by sequence for the HLA-DPB1 locus. Case/control and transmission disequilibrium test (TDT) methods revealed an association with the DPB1*030101 allele for JIA (OR 2.3, 95% CI 1.5-3.5). Notably, a detailed haplotypic analysis of the TAP2/TAP1 loci and their interaction with the HLA-DPB1*030101 and DRB1*08 and *11 alleles showed a variety of over-represented and under-represented TAP2/TAP1 haplotypes not evident in the single marker analysis. The strongest effect was observed in the polyarticular RF negative JIA subgroup for the 2-2-1-2-1 TAP2/TAP1 haplotype (TAP2B and TAP1A alleles) which showed an independent effect from both DRB1*08 and *11 (Po0.000003) and DPB1*030101 (P ¼ 0.02). We have provided evidence that the extended haplotypes (including HLA-DRB1, TAP2/TAP1, and HLA-DPB1) of pauciarticular and polyarticular RF negative disease are distinct. This observation may have implications for functional etiological differences between the pauciarticular and polyarticular JIA patients.

Classical HLA-DRB1 and DPB1 alleles account for HLA associations with primary biliary cirrhosis

“…These results are also consistent with findings in some, but not other, autoimmune diseases in which an independent effect of DPB1 has been reported. These include juvenile idiopathic arthritis 17 , type 1 diabetes 18 , multiple sclerosis 16, 19 and particular autoantibodies in systemic lupus erythematosus 20 .…”

Complexo Principal de Histocompatibilidade: sua participação na patogênese das doenças reumáticas auto-imunes

“…Estudos realizados com noruegueses e poloneses sugeriram a associação da AIJ com o alelo HLA-DRB1*08 (36) . Em finlandeses, essa associação ocorreu com os alelos HLA-DRB1*0801 e -DQB1*0402 (37) e em norteamericanos, com o -DPB1*030101 (38) . Na Colômbia, os alelos HLA-DRB1*1501 e -DRB1*1402 são encontrados menos freqüentemente em pacientes mestiços com AIJ (39) .…”