title: A distinct HLA-DRw8 haplotype characterizes patients with juvenile rheumatoid arthritis.
abstract: We studied the first domain of the HLA-DRB1, HLA-DQA1, and HLA-DQB1 loci of 67 HLA-DRw8-positive Caucasians including 43 with early-onset pauciarticular juvenile rheumatoid arthritis (EOPA-JRA, alternatively known as early-onset pauciarticular juvenile chronic arthritis). Serology, restriction fragment length polymorphism (RFLP), and polymerase chain reaction (PCR) oligotyping revealed that 62, including all the EOPA-JRA patients, carried the HLA-DRB1*0801, DQA1*0401, DQB1*0402 genotype. Approximately one-fifth of the controls carried atypical HLA-DRB1, HLA-DQA1, and/or HLA-DQB1 loci on their HLA-DRw8 haplotype confirmed by family studies. DNA sequences of HLA-DRB1, DQA1, and DQB1 alleles in patients and controls were identical to those previously reported. Disease association studies in 113 EOPA-JRA patients and 207 controls unselected for HLA-DRw8 revealed that the HLA-DRB1*0801, DQA1*0401, DQB1*0402 genotype was associated with a higher relative risk (RR) for disease (RR = 12.8, chi 2 = 48.8, P less than 10(-4)) than was the serologically defined presence of HLA-DRw8 (RR = 8, chi 2 = 39, P less than 10(-4)). Further analysis suggested that the DQ genes on HLA-DRw8 haplotypes are as likely as the DR genes to contribute to the pathogenesis of EOPA-JRA. This study increases to five the number of HLA-DR/DQ haplotypes identified in HLA-DRw8 Caucasians.
authors.affiliation: Children's Hospital Medical Center, Cincinnati, OH.
authors.forename: C
authors.initials: C
authors.lastname: Van Kerckhove
authors.forename: H
authors.initials: H
authors.lastname: Melin-Aldana
authors.forename: M S
authors.initials: MS
authors.lastname: Elma
authors.forename: L
authors.initials: L
authors.lastname: Luyrink
authors.forename: P
authors.initials: P
authors.lastname: Donnelly
authors.forename: J
authors.initials: J
authors.lastname: Taylor
authors.forename: W P
authors.initials: WP
authors.lastname: Maksymowych
authors.forename: D J
authors.initials: DJ
authors.lastname: Lovell
authors.forename: E
authors.initials: E
authors.lastname: Choi
authors.forename: D N
authors.initials: DN
authors.lastname: Glass
mesh_terms: D001171:Arthritis, Juvenile / Q000235:genetics* / Q000276:immunology; D001483:Base Sequence; D005500:Follow-Up Studies; D005838:Genotype; D006683:HLA-DQ Antigens / Q000235:genetics; D006684:HLA-DR Antigens / Q000235:genetics; D059810:HLA-DR Serological Subtypes; D006239:Haplotypes; D006801:Humans; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D044465:White People
chemical_list: D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens; D059810:HLA-DR Serological Subtypes; C041559:HLA-DR8 antigen