Sporadic inclusion body myositis: HLA-DRB1 allele interactions influence disease risk and clinical phenotype.

Susceptibility to sIBM is strongly associated with the HLA-DRB103 allele and the 8.1 MHC ancestral haplotype (HLA-A1, B8, DRB103) but little is known about the effects of allelic interactions at the DRB1 locus or disease-modifying effects of HLA alleles. HLA-A, B and DRB1 genotyping was performed in 80 Australian sIBM cases and the frequencies of different alleles and allele combinations were compared with those in a group of 190 healthy controls. Genotype-phenotype correlations were also investigated. Amongst carriers of the HLA-DRB103 allele, DRB103/01 heterozygotes were over-represented in the sIBM group (p<0.003) while. DRB103/04 heterozygotes were under-represented (p<0.008). The mean age-at-onset (AAO) was 6.5 years earlier in DRB103/01 heterozygotes who also had more severe quadriceps muscle weakness than the rest of the cohort. The findings indicate that interactions between the HLA-DRB103 allele and other alleles at the DRB1 locus can influence disease susceptibility and the clinical phenotype in sIBM.