Objective: To investigate the role of HLA-DRB1 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 DRB1 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 DRB1 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 DRB1 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.