Abstract

Broadly, this proposal examines the pathogenesis, and primarily the immunogenetic aspects, of Juvenile Rheumatoid Arthritis (JRA), the major crippling arthropathy of childhood. An immunogenetic (HLA) influence in this disease has been established; however, the critical predisposing genes and their products are unknown. Present knowledge of autoimmune diseases like JRA suggests that products of HLA genes and T-lymphocyte receptor genes interact with a putative disease-associated antigen to form a trimolecular complex that results in disease expression. The research proposed here is designed to identify the HLA genes and their products (epitopes) critical to formation of this complex in children with early onset pauciarticular types of JRA. HLA associations with this form of JRA are unique among childhood arthropathies. Specifically, HLA genes will be sequenced utilizing the polymerase chain reaction, to facilitate the process. The long-term goals of the project are the development of probes and antibodies that are epitope specific and can be used for future investigational, diagnostic, and perhaps therapeutic purposes.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR039979-02
Application #
3160228
Study Section
General Medicine A Subcommittee 2 (GMA)
Project Start
1989-06-15
Project End
1992-05-31
Budget Start
1990-06-01
Budget End
1991-05-31
Support Year
2
Fiscal Year
1990
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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