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.
Department of Pediatrics, College of Medicine, University of Cincinnati, OH 45229.
W P
WP
Maksymowych
C A
CA
Gabriel
L
L
Luyrink
H
H
Melin-Aldana
M
M
Elma
E H
EH
Giannini
D J
DJ
Lovell
C
C
Van Kerckhove
J
J
Leiden
E
E
Choi
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