Abstract

The hypothesis of this work is that the expression and regulation of IgG rheumatoid factor (RF) autoantibodies rather than IgM RF is important for the pathogenesis of rheumatoid arthritis (RA). The goal of this project is to identify and characterize genes involved in the production of these autoantibodies and to determine thr molecular basis of RF reactivity. Identification of pathogenic RF in RA is critical for the design of new and more specific therapies for the treatment of RA. 1. To isolate monoclonal IgG RF-producing cells from RA synovium. 2. To clone and sequence the genes expressed in IgG RF autoantibodies and compare them to those previously described for IgM RF. 3. To determine the contribution of heavy and light chains to RF reactivity and identify individual amino acids responsible for RF binding reactivity. 4. To determine if the expression of these RF autoantibodies is related to RA disease activity by measuring RF gene expression in peripheral blood lymphocytes (PBL) and in lymphocytes from the synovium of rheumatoid arthritis patients and normal individuals.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Comprehensive Center (P60)
Project #
5P60AR036834-09
Application #
2079162
Study Section
Arthritis and Musculoskeletal and Skin Diseases Special Grants Review Committee (AMS)
Project Start
1987-07-15
Project End
1997-08-31
Budget Start
1995-09-01
Budget End
1996-08-31
Support Year
9
Fiscal Year
1995
Total Cost
Indirect Cost

  Institution

Name
University of California Los Angeles
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
119132785
City
Los Angeles
State
CA
Country
United States
Zip Code
90095

  Publications

Jawaheer, Damini; Maranian, Paul; Park, Grace et al. (2010) Disease progression and treatment responses in a prospective DMARD-naive seropositive early rheumatoid arthritis cohort: does gender matter? J Rheumatol 37:2475-85
Ranganath, Veena K; Yoon, Jeonglim; Khanna, Dinesh et al. (2007) Comparison of composite measures of disease activity in an early seropositive rheumatoid arthritis cohort. Ann Rheum Dis 66:1633-40
Kahn, Katherine L; MacLean, Catherine H; Liu, Honghu et al. (2007) The complexity of care for patients with rheumatoid arthritis: metrics for better understanding chronic disease care. Med Care 45:55-65
Kahn, K L; Maclean, C H; Wong, A L et al. (2007) Assessment of American College of Rheumatology quality criteria for rheumatoid arthritis in a pre-quality criteria patient cohort. Arthritis Rheum 57:707-15
Kahn, K L; MacLean, C H; Liu, H et al. (2006) Application of explicit process of care measurement to rheumatoid arthritis: Moving from evidence to practice. Arthritis Rheum 55:884-91
La Cava, Antonio; Ebling, Fanny M; Hahn, Bevra H (2004) Ig-reactive CD4+CD25+ T cells from tolerized (New Zealand Black x New Zealand White)F1 mice suppress in vitro production of antibodies to DNA. J Immunol 173:3542-8
Amjadi-Begvand, Sogol; Khanna, Dinesh; Park, Grace S et al. (2004) Dating the ""window of therapeutic opportunity"" in early rheumatoid arthritis: accuracy of patient recall of arthritis symptom onset. J Rheumatol 31:1686-92
Wong, Andrew L; Harker, Judith O; Mittman, Brian S et al. (2004) Development and evaluation of a patient self-report case-finding method for rheumatoid arthritis. Semin Arthritis Rheum 34:484-99
Wu, Hui; Khanna, Dinesh; Park, Grace et al. (2004) Interaction between RANKL and HLA-DRB1 genotypes may contribute to younger age at onset of seropositive rheumatoid arthritis in an inception cohort. Arthritis Rheum 50:3093-103
Paulus, Harold E; Oh, MyungShin; Sharp, John T et al. (2004) Classifying structural joint damage in rheumatoid arthritis as progressive or nonprogressive using a composite definition of joint radiographic change: a preliminary proposal. Arthritis Rheum 50:1083-96

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