Project Details
Description
Our long-range objective is to understand the etiology of systemic lupus
erythematosus(SLE). Our present work has sought to provide a comprehensive
picture of the different antigen-antibody systems that involve
ribonucleoproteins in patients with this disease. The outcome has been the
development of the hypothesis that specific nucleoproteins, especially the
U1 snRNP, the nucleosome, and the Ro particle, actively elicit and possibly
propagate autoimmune responses in this disease. To develop this hypothesis
further, we are now concentrating our efforts to study the structure and
biologic function of the autoantigenic Ku protein--a newly discovered
chromatin component which we hypothesize plays a role in DNA repair or
transposition--and the Ro particle--which is a central focus of autoimmune
responses in patients with SLE. Work on the Ku protein will seek to establish its structure and biologic
function. We will use cloning and standard biochemical approaches to
characterize this protein structurally and to identify its autoantigenic
epitopes. In addition, we will seek to identify its function using a
variety of biological assay systems. Finally we will develop a new ELISA
for measurement of anti-Ku antibodies in clinical studies using recombinant
Ku protein as antigen. Work on the Ro particle will concentrate on developing specific
probes--including monoclonal antibodies--that recognize it, devising a
method for reconstituting it in vitro, and determining its location in
cells. In addition, we will compare patient sera with immunized animal
sera in terms of specific Ro protein epitopes recognized by each. This work will provide new information about the structure of the Ku
protein and the Ro particle. It may succeed in defining the biological
function of these newly recognized cellular elements. Information about
the structure and function of the Ku protein and the Ro particle could help
us understand why certain nucleoproteins become targets for selected
autoimmune responses in patients with SLE.
erythematosus(SLE). Our present work has sought to provide a comprehensive
picture of the different antigen-antibody systems that involve
ribonucleoproteins in patients with this disease. The outcome has been the
development of the hypothesis that specific nucleoproteins, especially the
U1 snRNP, the nucleosome, and the Ro particle, actively elicit and possibly
propagate autoimmune responses in this disease. To develop this hypothesis
further, we are now concentrating our efforts to study the structure and
biologic function of the autoantigenic Ku protein--a newly discovered
chromatin component which we hypothesize plays a role in DNA repair or
transposition--and the Ro particle--which is a central focus of autoimmune
responses in patients with SLE. Work on the Ku protein will seek to establish its structure and biologic
function. We will use cloning and standard biochemical approaches to
characterize this protein structurally and to identify its autoantigenic
epitopes. In addition, we will seek to identify its function using a
variety of biological assay systems. Finally we will develop a new ELISA
for measurement of anti-Ku antibodies in clinical studies using recombinant
Ku protein as antigen. Work on the Ro particle will concentrate on developing specific
probes--including monoclonal antibodies--that recognize it, devising a
method for reconstituting it in vitro, and determining its location in
cells. In addition, we will compare patient sera with immunized animal
sera in terms of specific Ro protein epitopes recognized by each. This work will provide new information about the structure of the Ku
protein and the Ro particle. It may succeed in defining the biological
function of these newly recognized cellular elements. Information about
the structure and function of the Ku protein and the Ro particle could help
us understand why certain nucleoproteins become targets for selected
autoimmune responses in patients with SLE.
| Status | Finished |
|---|---|
| Effective start/end date | 4/1/84 → 6/30/99 |
Funding
- National Institutes of Health
ASJC
- Medicine(all)
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