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Sponsored by: |
National Taiwan University Hospital |
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Information provided by: | National Taiwan University Hospital |
ClinicalTrials.gov Identifier: | NCT00364728 |
Over the past few years, growing evidences revealed that clearance of apoptotic cells by phagocytosis could result in powerful anti-inflammatory and immunosuppressive effects. In vivo, apoptotic cells are cleared rapidly by neighboring cells, macrophages and related scavengers. Defective clearance of apoptotic cells has been linked closely to autoimmunity and persistent inflammatory diseases. Several phagocytic receptors, bridging molecules produced by phagocytes and ‘eat-me’ signals on apoptotic cells are coordinately involved in mediating clearance of apoptotic cells. The best characterized system for clearance of apoptotic cells is the recognition of phosphatidylserine (PS) on apoptotic cells by phosphatidylserine receptor (PSR). Milk fat globule-epidermal growth factor 8 (MFG-E8) is an opsonin that bridges phagocytes and apoptotic cells. Activated macrophages produce and secret MFG-E8.
MFG-E8 is a critical component in PSR-mediated phagocytosis of apoptotic cells. The dominant negative mutant MFG-E8, D89E, that carried a mutated RGD motif inhibited phagocytosis of apoptotic cells in vitro. Injection of D89E into wild type mice induced autoantibodies and IgG deposition on glomeruli.
Macrophages from MFG-E8 deficiency (MFG-E8-/-) mice were impaired in engulfment of apoptotic cells, which can be restored by adding recombinant MFG-E8.
The female MFG-E8-/- mice spontaneously produced high titer of autoantibodies and developed lupus-like glomerulonephritis at the age of week 40.
Defective clearance of apoptotic cells is closely related to development of autoimmunity.
The specific aim of this proposal is to study genetic polymorphism in MFG-E8, and PSR among Taiwanese. By comparing the polymorphism between patients with autoimmune diseases (SLE or RA) and healthy control subjects, we will investigate if genetic variations among individuals of genes encoding proteins involved in clearance of apoptotic cells contribute to the pathogenesis or disease activity of systemic autoimmune diseases SLE and RA.
Condition |
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SLE Rheumatoid Arthritis Healthy Subjects |
Study Type: | Observational |
Study Design: | Screening, Cross-Sectional, Case Control, Retrospective Study |
Official Title: | Investigating Genetic Polymorphisms of Factors Related to Apoptotic Clearance, Milk Fat Globule Epidermal Growth Factor-8 (MFG-E8) and Phosphatidylserine Receptor (PSR), in Rheumatoid Arthritis and Systemic Lupus Erythrematosus. |
Estimated Enrollment: | 450 |
Study Start Date: | January 2006 |
Estimated Study Completion Date: | July 2009 |
Ages Eligible for Study: | 20 Years and older |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | Yes |
Inclusion Criteria: - SLE, RA, healthy Exclusion Criteria: - nil
Contact: Chung-Yi Hu, PhD | 886-2-2312-3456 ext 6914 | cyhu@ha.mc.ntu.edu.tw |
Contact: Ping-Ning Hsu, PhD | 886-2-23123456 ext 8635 | phsu@ha.mc.ntu.edu.tw |
Taiwan | |
Chung-Yi Hu | Recruiting |
Taipei, Taiwan, Taiwan, 100 | |
Contact: Chung-Yi Hu, PhD 886-2-23123456 ext 6914 cyhu@ha.mc.ntu.edu.tw | |
Contact: Ping-Ning Hsu, PhD 886-2-23123456 ext 8635 phsu@ha.mc.ntu.edu.tw | |
Principal Investigator: Chung-Yi Hu, PhD |
Principal Investigator: | Chung-Yi Hu, PhD | Department of Clinical Laboratory Sciences and Medical Biotechnology |
Study ID Numbers: | 9561701025, NSC95-2320-B-002-081 |
Study First Received: | August 15, 2006 |
Last Updated: | August 15, 2006 |
ClinicalTrials.gov Identifier: | NCT00364728 History of Changes |
Health Authority: | Taiwan: Department of Health |
Autoimmune Diseases Musculoskeletal Diseases Lupus Erythematosus, Systemic Lupus Joint Diseases Arthritis |
Connective Tissue Diseases Arthritis, Rheumatoid Mitogens Healthy Rheumatic Diseases |
Autoimmune Diseases Immune System Diseases Musculoskeletal Diseases Joint Diseases |
Arthritis Connective Tissue Diseases Arthritis, Rheumatoid Rheumatic Diseases |