Extended reports
Increase of HLA-DRB1*0408 and -DQB1*0301 in HLA-B27 positive
reactive arthritis
a Turku University, Turku, Finland:
Turku Immunology Centre and Department of
Medical Microbiology , b Department of Virology , c Turku
University Central Hospital, Turku, Finland:
Division of Rheumatology, Department of Medicine
, d Tampere
University Hospital, Tampere, Finland: Division
of Rheumatology, Department of Medicine
Correspondence to: Juha Tuokko MD, Department of Medical Microbiology, Turku University, Kiinamyllynkatu 13, FIN-20520, Turku, Finland.
Accepted for publication 21 October
1996
OBJECTIVE
To study HLA class II association in
reactive arthritis.
METHODS
63 patients with reactive arth-ritis 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).
HLA-B*2705 was by far the dominant B27 subtype both in reactive
arthritis patients with the particular DRB1*0408-DQB1*0301 haplotype
and in controls. It was found in 11 out of 12 DR analysed patients, as
well as in 10 out of 11 randomly selected B27 positive controls.
CONCLUSIONS
Although no single class II allele
was found to be increased among patients with reactive arthritis,
HLA-B27, DRB1*0408, and DQB1*0301 might exert a haplotypic effect in
the pathogenesis of reactive arthritis, or they may be markers of a
subset of B27 haplotypes conferring susceptibility.
© 1997 by Annals of the Rheumatic Diseases
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(2000). Immunogenetic differencies between patients with familial and non-familial rheumatoid arthritis. Ann Rheum Dis
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