Juvenile rheumatoid arthritis (JRA) is a family of illnesses characterized by chronic inflammation and hyperplasia of the synovial linings of joints. Its causes are unknown, and responses to treatment are often poor and associated with significant morbidity. Current theories of JRA pathogenesis have focused entirely on the role of T cells and adaptive immunity, failing to account for well-described abnormalities that implicate innate immunity in the disease process. We postulate that JRA pathogenesis involves complex interactions between innate and adaptive immunity. Traditional scientific approaches that focus narrowly and in depth on specific aspects of inflammation or immunity cannot grasp the complex pathogenesis at a single glance. DNA microarrays offer an ideal method for investigating these molecular interactions. Our preliminary experiments using DNA microarrays examined gene expression in peripheral blood buffy coat preparations from three children with polyarticular-onset JRA (poly-JRA). Our preliminary results indicate that the number of differentially expressed genes (compared to healthy age-matched controls) is 25-50 from an array of 2,400 genes. We now propose to continue to use buffy coat leukocyte preparations as the first step in identifying genes differentially expressed in additional children with active poly-JRA (Year 1). Once strong candidate genes have been identified, we will verify their expression and identify cellular localization in a single step using purified cell fractions (monocytes, granulocytes, and lymphocytes) and reverse transcriptase polymerase chain reaction (Year 2). We expect these pilot studies will provide the foundation for novel insights into the intersecting roles on innate and adaptive immunity in polyarticular JRA. Furthermore, these studies are likely to provide the basis for the elucidation of important prognostic markers and targets of novel therapies.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21AR048378-01A1
Application #
6560748
Study Section
Special Emphasis Panel (ZAR1-RJB-A (O1))
Program Officer
Serrate-Sztein, Susana
Project Start
2002-09-23
Project End
2004-05-31
Budget Start
2002-09-23
Budget End
2003-05-31
Support Year
1
Fiscal Year
2002
Total Cost
$73,250
Indirect Cost
Name
University of Oklahoma Health Sciences Center
Department
Pediatrics
Type
Schools of Medicine
DUNS #
937727907
City
Oklahoma City
State
OK
Country
United States
Zip Code
73117
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Jarvis, James N; Petty, Howard R; Tang, Yuhong et al. (2006) Evidence for chronic, peripheral activation of neutrophils in polyarticular juvenile rheumatoid arthritis. Arthritis Res Ther 8:R154
Jarvis, James N (2006) Gene expression arrays in juvenile rheumatoid arthritis: will the blind men finally see the elephant? Curr Probl Pediatr Adolesc Health Care 36:91-6
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Wright, Harlan; Alex, Philip; Nguyen, Thuan et al. (2005) Multiplex cytokine profiling of initial therapeutic response in patients with chronic hepatitis C virus infection. Dig Dis Sci 50:1793-803
Jarvis, James N; Centola, Michael (2005) Gene-expression profiling: time for clinical application? Lancet 365:199-200
Jarvis, James N (2005) Gene expression profiling in pediatric rheumatic disease: what have we learned? What can we learn? Curr Opin Rheumatol 17:606-11

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