INCREASE OF HLA-DRB1-ASTERISK-0408 AND HLA-DQB1-ASTERISK-0301 IN HLA-B27 POSITIVE REACTIVE ARTHRITIS

Objective-To study HLA class II association in reactive arthritis. Met hods-63 patients with reactive arthritis and 46 with rheumatoid arthri tis were included in the study. HLA-DR alleles were determined by usin g a sequence specific PCR method. Oligonucleotide hybridisation was us ed for definition of DRB104 subtypes and DQB1 alleles. HLA-B27 was de termined by standard microcytotoxity test or by PCR. HLA-B27 subtyping was made by sequencing. Results-46 (73%) of 63 patients with reactive arthritis were HLA-B27 positive and 24 (38%) were HLA-DRB104 positiv e. When haplotypes were inferred according to the known associations b etween DRB1 and DQB1 alleles, the frequency of DRB104-DQB1*0301 haplo type was found to be 13% (12/92) in HLA-B27 positive reactive arthriti s patients, in contrast to 0% in HLA-B27 negative reactive arthritis ( P = 0.04) and 1% in random controls (P = 0.0009). However, this combin ation was also found in 5% of 84 HLA-B27 positive control haplotypes, showing a linkage disequilibrium between B27 and this particular class II haplotype. HLA-DRB10408 subtype was found in 8/24 (33%) of the HL A-DRB104 alleles in patients with reactive arthritis, accounting for most DQB10301 haplotypes, but only in 5/55 (9%) of the DRB1*04 allele s in random controls (P = 0.017). All reactive arthritis patients with this subtype were positive for HLA-B27. DRB104-DQB1*0302 haplotype w as increased in patients with rheumatoid arthritis (28/92, 30%) compar ed with reactive arthritis (12/126, 10%) or with the controls (12/100, 12%; P = 0.003). HLA-B2705 was by far the dominant B27 subtype both in reactive arthritis patients with the particular DRB10408-DQB1*0301 haplotype and in controls. It was found in 11 out of 12 DR analysed p atients, as well as in 10 out of 11 randomly selected B27 positive con trols. Conclusions-Although no single class II allele was found to be increased among patients with reactive arthritis, HLA-B27, DRB10408, and DQB10301 might exert a haplotypic effect in the pathogenesis of r eactive arthritis, or they may be markers of a subset of B27 haplotype s conferring susceptibility.