APOPTOSIS-MODIFIED SELF ANTIGEN IN RHEUMATIC DISEASE

Project: Research project

Project Details

Description

DESCRIPTION: (adapted from applicant s abstract): The U1-70kDa
ribonucleoprotein, a prevalent autoantigen in rheumatic disease patients,
undergoes proteolytic cleavage in apoptosis. A model of autoimmune diseases
proposes that modified forms of self antigens can lead to recognition of
previously cryptic epitopes, allowing an auto-reactive immune response to
evolve. Thus, apoptotically modified Ul-70kDa is a candidate antigen that may
be involved in the evolution of autoimmune rheumatic diseases. The long-term
objective of this application is to develop an independent program of research
that leads to improved diagnosis, treatment, and prevention of rheumatic
diseases, based on an improved understanding of the contribution of
apoptotically modified self antigens to the generation of autoimmune
responses.

The following specific aims will examine the role of apoptotic Ul-70kDa in
autoimmune disease. First, it will be determined whether apoptotic Ul-70kDa is
antigenically distinct from intact Ul-70kDa. Sera from patients with intact
Ul-70kDa antibodies will be tested for antibodies specific for the apoptotic
form of U170kDa by ELISA and immunoblot. Immunoglobulins generated from Fab
phage expression libraries selected against apoptotic Ul-70kDa will also be
screened for apoptosis-specific Ul-70kDa reactivity. Epitope mapping will be
performed with all apoptotic Ul-70kDa specific antisera and Fab to identify
the immunologically distinct areas on the apoptotic form of the antigen.
Second, in a large cohort of rheumatic disease patients from whom multiple
serial blood samples have been drawn, it will be determined whether
anti-apoptotic U170kDa responses precede anti-intact Ul-70kDa immune
responses. As a result of this research, the contribution of apoptotic U1
-70kDa epitopes to the immunopathogenesis of rheumatic diseases will be
elucidated. Assays for antibodies to apoptotically modified Ul-70kDa with
potential clinical relevance to the diagnosis and management of rheumatic
diseases, will be developed. In the future, this work may lead to the
development of specific immunotherapy strategies for the treatment of
Ul-70kDa-associated rheumatic disorders.
StatusFinished
Effective start/end date9/30/0012/31/03

Funding

  • National Institute of Allergy and Infectious Diseases: $122,850.00
  • National Institute of Allergy and Infectious Diseases: $122,850.00
  • National Institute of Allergy and Infectious Diseases: $122,850.00

Fingerprint

Explore the research topics touched on by this project. These labels are generated based on the underlying awards/grants. Together they form a unique fingerprint.