A distinct HLA-DRw8 haplotype characterizes patients with juvenile rheumatoid arthritis |
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Authors: | Catherine Van Kerckhove Hector Melin-Aldana Maruja S. Elma Lorie Luyrink Patricia Donnelly Janalee Taylor Walter P. Maksymowych Daniel J. Lovell Edmund Choi David N. Glass |
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Affiliation: | (1) Children's Hospital Medical Center and the Departments of Pediatrics, University of Cincinnati School of Medicine, 45229 Cincinnati, OH, USA;(2) Molecular Genetics, Biochemistry, and Microbiology, University of Cincinnati School of Medicine, 45229 Cincinnati, OH, USA;(3) Present address: Dana Farber Cancer Institute, Laboratory of Immunochemistry, 02115 Boston, MA, USA;(4) Children's Hospital Medical Center, Elland and Bethesda Avenues, 45229-2899 Cincinnati, OH, USA |
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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 onefifth 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, 2 = 48.8, P < 10–4) than was the serologically defined presence of HLA-DRw8 (RR = 8, 2 = 39, P < 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.The nucleotide sequence data reported in this paper have been submitted to the GenBank nucleotide sequence database and have been assigned the accession number M34308. |
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