# MECHANISMS OF CUTANEOUS INJURY IN LUPUS ERYTHEMATOSUS

> **NIH NIH R01** · UT SOUTHWESTERN MEDICAL CENTER · 1991 · $218,978

## Abstract

Symptomatic and disfiguring cutaneous disease accounts for a considerable
degree of the physical and psychological disability which results from
lupus erythematosus (LE).  More knowledge concerning the clinical and
pathogenetic aspects of LE-specific skin disease could yield important new
insight into the pathogenesis of LE overall, and thereby provide improved
management strategies for the systemic as well as cutaneous manifestations
of this important human disorder.  The focus of the present application
will be upon the questions pertaining to skin lesion pathogenesis which are
raised by the striking relationship which exists between a humoral
autoimmune response to the Ro/SS-A (Ro) cellular ribonucleoprotein (RNP)
and LE-specific cutaneous disorders such as subacute cutaneous LE (SCLE)
and neonatal LE (NLE).  The specific aims of this application are:  1) TO
MORE FULLY ELUCIDATE THE MOLECULAR AND GENETIC ASPECTS OF THE Ro
AUTOANTIGEN SYSTEM.  The genomic configuration of a human Ro gene expressed
by Wil-2 lymphoblastoid cells will be determined and its gene product
characterized by epitope mapping, RNA binding site analysis and in vitro
translation.  In addition, this gene product will be compared to other Ro
RNP isoforms which might be expressed by human epidermal keratinocytes.  2)
TO FURTHER EXAMINE THE HYPOTHESIS THAT AN AUTOIMMUNE RESPONSE TO THE Ro
AUTOANTIGEN SYSTEM IS PRIMARILY RESPONSIBLE FOR THE PATHOGENESIS OF
SCLE/NEONATAL SKIN INJURY.  The link between photosensitivity in SCLE/NLE
patients and the humoral autoimmune response to the Ro RNP will be examined
by determining the impact of ultraviolet light (UVL) exposure upon Ro gene
transcription/translation in epidermal keratinocytes and characterizing the
impact of UVL upon Ro RNP structure and antigenicity.  The pathogenetic
role played by a cell-mediated autoimmune response to Ro antigens will be
examined by attempting to isolate Ro antigen-specific T cell clones from
SCLE skin lesions and develop an animal model of SCLE with Ro-specific T
cell clones.  3) TO EXAMINE THE FEASIBILITY OF DEVELOPING A TRANSGENIC
MOUSE MODEL OF SCLE/NEONATAL LE.  As the initial step toward developing a
versatile transgenic animal model of SCLE/NLE, an attempt will be made to
develop an inducible Ro fusion gene that can be expressed in murine
fibroblasts in vitro.  4) TO CARRY OUT A 10 YEAR FOLLOW-UP STUDY OF 115
PATIENTS.  In addition, to providing insight into the immunopathogenesis of
LE-specified skin disease, the above studies could yield important new
insight into the functional significance of the Ro RNP family in cell
biology.

## Key facts

- **NIH application ID:** 3155031
- **Project number:** 5R01AR019101-15
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **SAM.gov UEI:** YZJ6DKPM4W63
- **Principal Investigator:** Richard Dennis Sontheimer
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1991
- **Award amount:** $218,978
- **Award type:** 5
- **Project period:** 1979-05-01 → 1994-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3155031

## Citation

> US National Institutes of Health, RePORTER application 3155031, MECHANISMS OF CUTANEOUS INJURY IN LUPUS ERYTHEMATOSUS (5R01AR019101-15). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3155031. Licensed CC0.

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