# ROLE OF DNA IN SYSTEMIC LUPUS

> **NIH NIH R01** · UNIVERSITY OF COLORADO DENVER · 1991 · $162,859

## Abstract

Systemic Lupus Erythematosus (SLE) is the prototype autoimmune
disease, characterized clinically by glomerulonephritis and
vasculitis and immunologically by the production of multiple
autoantibodies.  Of these autoantibodies, antibodies (Abs) to
dsDNA correlate strongly with disease activity, and evidence
suggests they play a direct role in the pathogenesis of tissue
damage.  DNA Abs could potentially exert their pathogenic
effects in 3 ways:  1.) binding to DNA to form pathogenic immune
complexes (IC), 2.) binding directly to tissue antigens, or 3.)
directly modifying cell function.  The focus of this grant has been
to study the formation and clearance of DNA IC; we have studied
the clearance of extracellular DNA to investigate how DNA might
become available for Ab binding, and we have studied the in vivo
behavior of model DNA IC.  During these studies, we identified a
subset of DNA Abs, the presence of which correlates with SLE
disease activity.  We now propose:  1.) to characterize this subset
of DNA Abs to understand its pathogenicity, 2.) to extend our
studies on DNA IC, and 3.) to begin studies on mechanisms by
which DNA Abs might be pathogenic other than by the formation
of DNA IC.

1.)  Ab subsets which bind DNA by monogamous bivalent binding
or by cross-linking DNA have been identified.  The basis for this
difference will be studied by examining the binding specificity and
avidity of each Ab type.  Clinical associations with each Ab type
will be sought.  2)  The in vivo behavior of defined IC made with
both Ab subsets will be examined (mice); the effect of IC size and
Ab/Ag ratio will be studied.  Since DNA binds to Clq, we will also
study C1 activation of these DNA IC.  To examine the possibility
that DNA Abs cross-react with tissue antigens, binding of DNA
Abs directly to renal tissue will be studied using a renal perfusion
model.  3.)  The DNA receptor will be isolated from Kupffer cells
and characterized.

These studies should define parameters which control the
clearance of DNA IC, and directly address the question of cross-
reactivity of DNA Abs with tissue (renal) antigens.  In addition,
we will begin to address the broader question of the physiologic
role of the DNA receptor.

## Key facts

- **NIH application ID:** 3155258
- **Project number:** 5R01AR024015-14
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **SAM.gov UEI:** MW8JHK6ZYEX8
- **Principal Investigator:** Woodruff Emlen
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1991
- **Award amount:** $162,859
- **Award type:** 5
- **Project period:** 1987-09-01 → 1992-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3155258

## Citation

> US National Institutes of Health, RePORTER application 3155258, ROLE OF DNA IN SYSTEMIC LUPUS (5R01AR024015-14). Retrieved via MORVS 2026-10-24 from https://api.morvs.ai/grant/nih/3155258. Licensed CC0.

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