Polymorphism in a T-cell receptor variable gene is associated with susceptibility to a juvenile rheumatoid arthritis subset.
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 less than 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.
Maksymowych
W P
WP
Department of Pediatrics, College of Medicine, University of Cincinnati, OH 45229.
Gabriel
C A
CA
Luyrink
L
L
Melin-Aldana
H
H
Elma
M
M
Giannini
E H
EH
Lovell
D J
DJ
Van Kerckhove
C
C
Leiden
J
J
Choi
E
E
D001171:Arthritis, Juvenile / Q000235:genetics*; D001426:Bacterial Proteins; D001483:Base Sequence; D002897:Chromosomes, Human, Pair 7; D015252:Deoxyribonucleases, Type II Site-Specific / Q000378:metabolism; D006683:HLA-DQ Antigens / Q000235:genetics*; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D008969:Molecular Sequence Data; D012150:Polymorphism, Restriction Fragment Length; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*; D044465:White People / Q000235:genetics
D001426:Bacterial Proteins; D006683:HLA-DQ Antigens; D007135:Immunoglobulin Variable Region; D016693:Receptors, Antigen, T-Cell, alpha-beta; C024404:BglII endonuclease; D015252:Deoxyribonucleases, Type II Site-Specific