Efferocytosis and Genomic Polymorphism in Autoimmune Diseases

NCT00364728 | Unknown

• 2 other identifiers: 9561701025NSC98-2320-B-002-021-MY2
• Study Type: observational
• Target: 450
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

SLE; Rheumatoid Arthritis; Healthy Subjects

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Taiwan autoimmune diseases case control study

You may qualify if:

• SLE, RA, healthy

You may not qualify if:

• nil

Sponsors & Collaborators

• National Taiwan University Hospital: lead

Study Sites (1)

Chung-Yi Hu

Taipei, Taiwan, 100, Taiwan

RECRUITING

MeSH Terms

Conditions

Arthritis, Rheumatoid

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Chung-Yi Hu, PhD

  Department of Clinical Laboratory Sciences and Medical Biotechnology

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Chung-Yi Hu, PhD

CONTACT

886-2-2312-3456; jcyhu@ntu.edu.tw

Ping-Ning Hsu, PhD

CONTACT

886-2-23123456; phsu8635@ntu.edu.tw

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: August 15, 2006
• First Posted: August 16, 2006
• Study Start: January 1, 2006
• Primary Completion: July 1, 2012
• Study Completion: July 1, 2012
• Last Updated: May 21, 2010

Record last verified: 2010-05

Locations

TW (1)