HLA-DQ beta 3.1 allele is a determinant of susceptibility to DR4-associated rheumatoid arthritis.

Abstract:

:Rheumatoid arthritis is associated with HLA-DR4 in several ethnic groups. Since DR4 haplotypes encode a diverse array of class II molecules, it is of interest to characterize the nature of the primary association. We have examined molecular polymorphisms of HLA class II gene products expressed by normals and rheumatoid arthritis patients using monoclonal antibodies and two-dimensional electrophoresis. Most homozygous DR4 rheumatoid arthritis patients express DR beta 1 molecules associated with Dw4 or Dw14 mixed lymphocyte culture determinants. In Caucasoids, two DR4-linked DQw3-associated beta-chain alleles are defined by two-dimensional electrophoresis. These variants, designated DQ beta 3.1 and 3.2, are associated with the serologic determinants DQw7 and DQw8, respectively. A panel of 40 DR4-positive normals was also examined for nucleotide sequence polymorphisms associated with DQB3.1 and 3.2 genes using the polymerase chain reaction and specific oligonucleotide probes. At the DQ beta level the rheumatoid arthritis panel was distinguished by enrichment for the DQ beta 3.1 allele with 100% of patients positive for DQw7. Results presented here suggest that specific DQ beta alleles may modify the effect of HLA-DR4 beta 1 alleles in conferring susceptibility to rheumatoid arthritis in a phenotype-specific fashion.

journal_name

Hum Immunol

journal_title

Human immunology

authors

Lanchbury JS,Sakkas LI,Marsh SG,Bodmer JG,Welsh KI,Panayi GS

doi

10.1016/0198-8859(89)90033-5

subject

Has Abstract

pub_date

1989-09-01 00:00:00

pages

59-71

issue

1

eissn

0198-8859

issn

1879-1166

pii

0198-8859(89)90033-5

journal_volume

26

pub_type

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