Efferocytosis and Genomic Polymorphism in Autoimmune Diseases

The recruitment status of this study is unknown because the information has not been verified recently.
Verified May 2010 by National Taiwan University Hospital.
Recruitment status was  Recruiting
Sponsor:
Information provided by:
National Taiwan University Hospital
ClinicalTrials.gov Identifier:
NCT00364728
First received: August 15, 2006
Last updated: May 20, 2010
Last verified: May 2010
  Purpose

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
SLE
Rheumatoid Arthritis
Healthy Subjects

Study Type: Observational
Study Design: Observational Model: Case Control
Time Perspective: Retrospective
Official Title: Efferocytosis (Clearance of Apoptotic Cells by Phagocytosis) and Autoimmune Diseases in Human

Resource links provided by NLM:


Further study details as provided by National Taiwan University Hospital:

Estimated Enrollment: 450
Study Start Date: January 2006
Estimated Study Completion Date: July 2012
Estimated Primary Completion Date: July 2012 (Final data collection date for primary outcome measure)
  Show Detailed Description

  Eligibility

Ages Eligible for Study:   20 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

Taiwan autoimmune diseases case control study

Criteria

Inclusion Criteria:

  • SLE, RA, healthy

Exclusion Criteria:

  • nil
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00364728

Contacts
Contact: Chung-Yi Hu, PhD 886-2-2312-3456 ext 66914 jcyhu@ntu.edu.tw
Contact: Ping-Ning Hsu, PhD 886-2-23123456 ext 88635 phsu8635@ntu.edu.tw

Locations
Taiwan
Chung-Yi Hu Recruiting
Taipei, Taiwan, Taiwan, 100
Contact: Chung-Yi Hu, PhD    886-2-23123456 ext 66914    jcyhu@ntu.edu.tw   
Contact: Ping-Ning Hsu, PhD    886-2-23123456 ext 88635    phsu8635@ntu.edu.tw   
Principal Investigator: Chung-Yi Hu, PhD         
Sponsors and Collaborators
National Taiwan University Hospital
Investigators
Principal Investigator: Chung-Yi Hu, PhD Department of Clinical Laboratory Sciences and Medical Biotechnology
  More Information

No publications provided

Responsible Party: National Taiwan University Hospital research ethics committee, National Taiwan University Hospital
ClinicalTrials.gov Identifier: NCT00364728     History of Changes
Other Study ID Numbers: 9561701025, NSC98-2320-B-002-021-MY2
Study First Received: August 15, 2006
Last Updated: May 20, 2010
Health Authority: Taiwan: Department of Health

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Autoimmune Diseases
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Immune System Diseases

ClinicalTrials.gov processed this record on September 11, 2014