Efferocytosis and Genomic Polymorphism in Autoimmune Diseases
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|ClinicalTrials.gov Identifier: NCT00364728|
Recruitment Status : Unknown
Verified May 2010 by National Taiwan University Hospital.
Recruitment status was: Recruiting
First Posted : August 16, 2006
Last Update Posted : May 21, 2010
Over the past few years, growing evidences revealed that clearance of apoptotic cells by phagocytosis can 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 disease. Several phagocytic receptors, bridging molecules produced by phagocytes and 'eat-me' signals on apoptotic cells are coordinately involved in mediating clearance of apoptotic cells. Complement receptors (CR3, CR4), collection, CD14, CD36 (Class B scavenger receptor), class A scavenger receptor, asialoprotein receptor, Mer receptor kinase were reported to recognize 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 (by interacting with α vβ3, αvβ5 integrins via RGD motif) and apoptotic cells (by binding PS through Factor V/VIII-C domain). 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. In the past 4 years, a growing number of molecules were recognized as receptors for the PS exposed on the apoptotic cells. These molecules were capable of mediating phagocytic clearance, rendering anti-inflammatory cytokines in the phagocytes, and modulating T cell responses.
The specific aim of this proposal is to study genetic polymorphism in MFG-E8, PSR and other factors implicated in phagocytic clearance of apoptotic cells among Taiwanese. By comparing the polymorphism between patients with autoimmune disease (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 of systemic autoimmune diseases SLE and RA.
|Condition or disease|
|SLE Rheumatoid Arthritis Healthy Subjects|
Show Detailed Description
|Study Type :||Observational|
|Estimated Enrollment :||450 participants|
|Observational Model:||Case Control|
|Official Title:||Efferocytosis (Clearance of Apoptotic Cells by Phagocytosis) and Autoimmune Diseases in Human|
|Study Start Date :||January 2006|
|Estimated Primary Completion Date :||July 2012|
|Estimated Study Completion Date :||July 2012|
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00364728
|Contact: Chung-Yi Hu, PhD||886-2-2312-3456 ext email@example.com|
|Contact: Ping-Ning Hsu, PhD||886-2-23123456 ext firstname.lastname@example.org|
|Taipei, Taiwan, Taiwan, 100|
|Contact: Chung-Yi Hu, PhD 886-2-23123456 ext 66914 email@example.com|
|Contact: Ping-Ning Hsu, PhD 886-2-23123456 ext 88635 firstname.lastname@example.org|
|Principal Investigator: Chung-Yi Hu, PhD|
|Principal Investigator:||Chung-Yi Hu, PhD||Department of Clinical Laboratory Sciences and Medical Biotechnology|