Abstract

1.) To study the role of B-lymphoid progenitors in the development of systemic lupus using a combination of in vitro and in vivo approaches; 2.) To study the possible role of abnormal programmed cell death and altered growth regulation of B-progenitors in initiation of these events. Systemic lupus results from abnormal B-cell activation. A primary defect(s) present in bone marrow progenitor cells of lupus prone animals is essential in the initiation of this abnormal B-cell activation. Expression of the defect may be limited to B- and/or T-progenitors or, alternatively, affect multiple lineages. A candidate gene for this defect may affect apoptosis, the process of programmed cell death. For example, overexpression of Bcl-2, a proto-oncogene inhibiting apoptosis, results in systemic lupus erythematosus (SLE)-like disease and is one genetic model of systemic autoimmunity. We will investigate the role of abnormal apoptosis both as model for the development of systemic autoimmunity and as one possible genetic abnormality in SLE.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Comprehensive Center (P60)
Project #
5P60AR036834-08
Application #
3747841
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
8
Fiscal Year
1994
Total Cost
Indirect Cost

  Institution

Name
University of California Los Angeles
Department
Type
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
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
Liu, Honghu; Harker, Judith O; Wong, Andrew L et al. (2004) Case finding for population-based studies of rheumatoid arthritis: comparison of patient self-reported ACR criteria-based algorithms to physician-implicit review for diagnosis of rheumatoid arthritis. Semin Arthritis Rheum 33:302-10
Riemekasten, Gabriela; Langnickel, Dirk; Enghard, Philipp et al. (2004) Intravenous injection of a D1 protein of the Smith proteins postpones murine lupus and induces type 1 regulatory T cells. J Immunol 173:5835-42

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