Role of HLA-DR-DR and DR-DQ associations in the expression of extraarticular manifestations and rheumatoid factor in rheumatoid arthritis

Objective. To investigate the role of HLA-DRB I genotypes and HLA-DRB1*0401-DQB1*03 haplotypes in the expression of extraarticular manifestations and rheumatoid factor (RF) in rheumatoid arthritis (RA). Methods. 189 patients with RA were classified according to the presence of vasculitis and seropositivity for RF. IgM RF were determined by at least 2 of the following methods standard latex agglutination, the Waaler-Rose test, and nephelometry. HLA genotyping was performed by reverse dot blot hybridization for DRBI alleles and the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method for DQB1 alleles. Results. The QKRAA susceptibility sequence, which characterizes the HLA-DRB1*0401 allele, was observed in 71.5% of the 21 patients with vasculitis and 57.6% of the 158 RF positive patients. The influence of a 2nd allele within the major histocompatibility complex was observed but the allele differed according to the clinical features examined. Higher risk for vasculitis was observed in patients who carried 2 DRB I susceptibility alleles, one characterized by the QKRAA sequence and the other by the QRRAA sequence (OR = 3). Conversely. the higher risk for IgM RF positivity was observed in patients who carried the QKRAA sequence of the DRB alleles with the DQB1*0301 alleles of the DQ region (OR = 4.7). Conclusion. Our data suggest that a distinct immunogenetic association is involved in the extraarticular manifestations of RA and in the expression of RF.