Increase of HLA-DRB1*0408 and -DQB1*0301 in HLA-B27 positive reactive arthritis

Abstract

Objective-To study HLA class II association in reactive arthritis. Methods-63 patients with reactive arthritis and 46 with rheumatoid arthritis were included in the study. HLA-DR alleles were determined by using a sequence specific PCR method. Oligonucleotide hybridisation was used for definition of DRB1*04 subtypes and DQB1 alleles. HLA-B27 was determined 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-DRB1*04 positive. When haplotypes were inferred according to the known associations between DRB1 and DQB1 alleles, the frequency of DRB1*04-DQB1*0301 haplotype was found to be 13% (12/92) in HLA-B27 positive reactive arthritis patients, in contrast to 0% in HLA-B27 negative reactive arthritis (P = 0.04) and 1% in random controls (P = 0.0009). However, this combination 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-DRB1*0408 subtype was found in 8/24 (33%) of the HLA-DRB1*04 alleles in patients with reactive arthritis, accounting for most DQB1*0301 haplotypes, but only in 5/55 (9%) of the DRB1*04 alleles in random controls (P = 0.017). All reactive arthritis patients with this subtype were positive for HLA-B27. DRB1*04-DQB1*0302 haplotype was increased in patients with rheumatoid arthritis (28/92, 30%) compared with reactive arthritis (12/126, 10%) or with the controls (12/100, 12%; P = 0.003).

Immunogenetic differencies between patients with familial and non-familial rheumatoid arthritis

“…In addition to the HLA-DR4 subtypes *0401, *0404 and *0408 the subtype *0405 belongs to those so called RA risk alleles. It, however, is very rare in the healthy Finnish population42 and we could not find any DRB1*0405 positive persons either in the familial or the non-familial group. The increased frequency of DR4 in familial RA patients was also reflected in the higher amount of so called SE in them.…”

“…There were only four (3.1%) patients in the familial and eight (3.7%) patients in the non-familial group with that allele combination. HLA-DRB1*0401 and *0404 are the two common subtypes in our population42 and these known RA associated HLA-DR4 subtypes were found in equal frequencies in both our familial and non-familial RA groups, the subtype *0401 was more frequent than *0404 in both study groups. McDonagh and coworkers found a relatively high prevalence of DRB1*0408 (16.7%) in their familial RA patients (no non-familial patients) and suggested the possibility that the DRB1*0408 allele may have a more important role in familial RA 43.…”

“…We have earlier described this HLA-B27 positive haplotype in reactive arthritis42 and RA44 where we suggested that it might explain the increased frequency of B27 reported in Finnish RA patients. In this study the frequency of B27 among non-familial patients was similar to that reported for Finnish controls45 46 and we could not confirm its higher frequency in RA patients; in familial cases it was only marginally increased (19.4 v 14.4%; NS).…”

Mucous membrane pemphigoid: HLA-DQB1*0301 is associated with all clinical sites of involvement and may be linked to antibasement membrane IgG production

“…35 DQB1*0301 has also been reported in association with the closely related disorder BP, in which circulating autoantibodies target similar BMZ antigens. 16,36 Sarcoidosis has been associated with DQB1*0301-bearing haplotypes, 37 reactive arthritis with HLA-B27/ DRB1*0408/DQB1*0301, 38 alopecia areata with DRB1*1104 and DQB1*0301 39 and lichen sclerosus with DR4/DQ7. 40 In conclusion, our study confirms that the majority of patients with MMP share a common genetic predisposition.…”

Cytochrome P450 1A1 and manganese superoxide dismutase genes polymorphisms in reactive arthritis

“…Tuokko et al also showed an increased TNFc1 frequency in patients with reactive arthritis independently of HLA-B27 [5]. TNFc1 might also be a new susceptibility marker for reactive arthritis.…”