Objective. To further characterize the HLA gene products that play an impor
tant role in the pathogenesis of rheumatoid arthritis (RA).
Methods. One hundred thirty-four haplotypes from 67 Finnish RA patients and
77 control haplotypes were analyzed for HLA-DRB1 loci, associated alleles
of the HLA-DQB1 locus, alleles of the type 2 transporter-associated antigen
processing (TAP2) genes, and HLA-B27. In addition, a panel of microsatelli
te markers within the HLA class I and class III regions was studied.
Results. The frequency of HLA-DRB1*04 in the haplotypes of RA patients was
found to be 34% (45 of 134) compared with 14% (10 of 72) in control haploty
pes (P = 0.004). The frequency of HLA-DRB1*13 was decreased in RA haplotype
s (4%, or 5 of 134) in contrast to control haplotypes (24%, or 17 of 72) (P
= 0.000031). The decrease in DRB1*13 was not secondary to the increase in
DRB1*04, since it was also found among DRB1*04-negative haplotypes (P < 0.0
01). The DRB1*13-associated DQB1*0604 allele was similarly decreased in RA
haplotypes (P = 0.025). The TAP2I allele of I/J dimorphism was increased in
RA patients (85%, or 114 of 134) as compared with controls (69%, or 49 of
71) (P = 0.011). Of the tumor necrosis factor (TNF) microsatellite alleles,
TNFa6 and TNFb5 were found to be increased in RA haplotypes (for a6 27% ve
rsus 5% in controls [P = 0.00043], and for b5 43% versus 26% in controls [P
= 0.037]).
Conclusion. Both protection-associated and susceptibility-associated allele
s can be found among HLA class II genes, and the results suggest that loci
outside DR/DQ may contribute to the pathogenesis of RA.