Abstract

Pauci JRA is the commonest chronic inflammatory arthritis of childhood. The etiology is unknown, well documented but unusually complex HLA gene associations indicate a genetic component in pathogenesis. This proposal tests the hypothesis that HLA interacts with antigen or superantigen to activate specific receptors (TCR) as part of a trimolecular complex. Accordingly, patterns of TCR expression will be sought in affected joints, the specificity for pauci JRA, will be established by comparison with other types of JRA. The laboratory methods to be used include PCR in a semi-quantitative manner and DNA sequencing. Essential to the project is the availability of a large cohort of comprehensive HLA-type patients with pauci JRA in the Children's Hospital Medical Center, as well as synovial fluid and synovial lining obtained during the management of their disease. In establishing roles for TCRs in JRA, these studies will enhance our understanding of the immunopathology of the disease. The knowledge generated by the proposal will have the potential to result in disease- specific therapeutic options, for example the use of TCR-specific monoclonal antibodies to treat the disease, part of the longterm goals of the study.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR039979-07
Application #
2006184
Study Section
General Medicine A Subcommittee 2 (GMA)
Project Start
1989-06-15
Project End
1998-08-31
Budget Start
1996-12-01
Budget End
1998-08-31
Support Year
7
Fiscal Year
1997
Total Cost
Indirect Cost

  Institution

Name
Cincinnati Children's Hospital Medical Center
Department
Type
DUNS #
071284913
City
Cincinnati
State
OH
Country
United States
Zip Code
45229

  Publications

Barnes, M G; Aronow, B J; Luyrink, L K et al. (2004) Gene expression in juvenile arthritis and spondyloarthropathy: pro-angiogenic ELR+ chemokine genes relate to course of arthritis. Rheumatology (Oxford) 43:973-9
Scola, Michael P; Thompson, Susan D; Brunner, Hermine I et al. (2002) Interferon-gamma:interleukin 4 ratios and associated type 1 cytokine expression in juvenile rheumatoid arthritis synovial tissue. J Rheumatol 29:369-78
Prahalad, S; Kingsbury, D J; Griffin, T A et al. (2001) Polymorphism in the MHC-encoded LMP7 gene: association with JRA without functional significance for immunoproteasome assembly. J Rheumatol 28:2320-5
Thompson, S D; Luyrink, L K; Graham, T B et al. (2001) Chemokine receptor CCR4 on CD4+ T cells in juvenile rheumatoid arthritis synovial fluid defines a subset of cells with increased IL-4:IFN-gamma mRNA ratios. J Immunol 166:6899-906
Scola, M P; Imagawa, T; Boivin, G P et al. (2001) Expression of angiogenic factors in juvenile rheumatoid arthritis: correlation with revascularization of human synovium engrafted into SCID mice. Arthritis Rheum 44:794-801
Prahalad, S; Ryan, M H; Shear, E S et al. (2000) Juvenile rheumatoid arthritis: linkage to HLA demonstrated by allele sharing in affected sibpairs. Arthritis Rheum 43:2335-8
Glass, D N; Giannini, E H (1999) Juvenile rheumatoid arthritis as a complex genetic trait. Arthritis Rheum 42:2261-8
Murray, K J; Moroldo, M B; Donnelly, P et al. (1999) Age-specific effects of juvenile rheumatoid arthritis-associated HLA alleles. Arthritis Rheum 42:1843-53
Thompson, S D; Murray, K J; Grom, A A et al. (1998) Comparative sequence analysis of the human T cell receptor beta chain in juvenile rheumatoid arthritis and juvenile spondylarthropathies: evidence for antigenic selection of T cells in the synovium. Arthritis Rheum 41:482-97
Murray, K J; Grom, A A; Thompson, S D et al. (1998) Contrasting cytokine profiles in the synovium of different forms of juvenile rheumatoid arthritis and juvenile spondyloarthropathy: prominence of interleukin 4 in restricted disease. J Rheumatol 25:1388-98

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