Pauciarticular juvenile rheumatoid arthritis Type I (Pauci I JRA) is a relatively common inflammatory disease of childhood which, like a large number of """"""""autoimmune"""""""" diseases, is associated with certain HLA Class II specificities. A number of investigators has demonstrated the association of this form of JRA with the HLA determinants DR5, 6, and/or 8, although the basis of this association is not understood. A growing body of information has advanced our understanding of the complexity of genetic haplotypes represented by each serologically-defined HLA determinant. For example, we have previously shown that the specificity HLA-DR4 actually encompasses at least 5 different expressed polypeptides encoded by the DR locus genes; the closely-linked specificity HLA-DQw3 likewise contains at least 3 electrophoretically distinct proteins and a larger number of restriction fragment length polymorphisms (RFLP), indicating broad nucleotide variation. Similar complexity of the Pauci I JRA-associated specifications HLA-DR5, 6, and 8 is emerging. We hypothesize that a common structural basis exists among the HLA Class II specificities associated with Pauci I JRA. The objectives of this study are to identify certain serologic and structural polymorphisms within these disease-associated haplotypes which may account for their correlation with disease; to determine whether the presence of more than one HLA- encoded element increases disease risk, and, if so, whether this represents gene complementation; and to investigate the possible predictive value of certain structural polymorphisms to particular clinical manifestations, such as the presence of uveitis.

Project Start
1987-07-01
Project End
1992-06-30
Budget Start
1989-07-01
Budget End
1990-06-30
Support Year
3
Fiscal Year
1989
Total Cost
Indirect Cost
Name
Benaroya Research Institute at Virginia Mason
Department
Type
DUNS #
City
Seattle
State
WA
Country
United States
Zip Code
98101
Nepom, B S; Malhotra, U; Schwarz, D A et al. (1991) HLA and T cell receptor polymorphisms in pauciarticular-onset juvenile rheumatoid arthritis. Arthritis Rheum 34:1260-7
Nepom, B S; Schwarz, D A; Johnston, J V et al. (1989) HLA-DQ alpha polymorphisms: oligonucleotide probes characterize the contribution of first and second domains to electrophoretic variants. Hum Immunol 25:257-67
Begovich, A B; Bugawan, T L; Nepom, B S et al. (1989) A specific HLA-DP beta allele is associated with pauciarticular juvenile rheumatoid arthritis but not adult rheumatoid arthritis. Proc Natl Acad Sci U S A 86:9489-93