Polymorphism in a T-cell receptor variable gene is associated with susceptibility to a juvenile rheumatoid arthritis subset |
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Authors: | Walter P Maksymowych Christos A Gabriel Lorie Luyrink Hector Melin-Aldana Maruja Elma Edward H Giannini Daniel J Lovell Catherine Van Kerckhove Jeffrey Leiden Edmund Choi David N Glass |
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Institution: | (1) Department of Pediatrics, College of Medicine, University of Cincinnati, 45229, OH, USA;(2) Department of Molecular Genetics, Biochemistry and Microbiology, College of Medicine, University of Cincinnati, 45229, OH, USA;(3) Departments of Internal Medicine and Microbiology/Immunology, Howard Hughes Medical Institute, University of Michigan Medical Center, Ann Arbor, MI, USA;(4) Special Treatment Center for Juvenile Arthritis, Children's Hospital Medical Center, Elland and Bethesda Avenues, Pav 1–129, 45229-2899 Cincinnati, OH, USA |
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Abstract: | This report demonstrates a T-cell receptor (Tcr) restriction fragment length polymorphism, defined by a Tcrb-V6.1 gene probe and Bgl II restriction enzyme, to be absolutely correlated with allelic variation in the coding sequence of a Tcrb-V6.1 gene. A pair of non-conservative amino acid substitutions distinguish the Tcrb-V6.1 allelic variants. An association of this Tcrb-V6.1 gene allelic variant with one form of juvenile rheumatoid arthritis (JRA) was established in a cohort of 126 patients. The association was observed in patients possessing the HLA-DQA1*0101 gene. Among HLA-DQA*0101 individuals, 19 of 26 patients (73.1%) carried one particular Tcrb-V6.1 gene allele as opposed to 11 of 33 controls (33%; p<0.005). Haplotypes carrying this HLA gene have previously been shown to confer increased risk for progression of arthritis in JRA. This demonstration of a disease-associated Tcrb-V gene allelic variant has not, to our knowledge, been previously reported and supports the contribution of polymorphism in the Tcr variable region genomic repertoire to human autoimmune disease.The nucleotide sequence data reported in this paper have been submitted to the GenBank nucleotide sequence database and have been assigned the accession numbers M67511 for V6.1A and M67512 for V6.1B. |
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