# CYTOTOXIC MECHANISMS IN CUTANEOUS DISEASE

> **NIH NIH R01** · UNIVERSITY OF COLORADO DENVER · 1988 · $164,401

## Abstract

The objective of this project is to study immunologic cytotoxicity as a
mechanism of discrete cellular lysis in cutaneous disease, with particular
emphasis on antibody mediated mechanisms of lysis, especially antibody
dependent cellular cytotoxicity (ADCC).  The principle focus of this
project is on ADCC as a mechanism of photosensitive papulosquamous
cutaneous lupus erythematosus, attempting to explain the strong association
of anti SSA antibodies to this clinical condition, by testing the
hypothesis that SSA antigen induced by ultraviolet light on keratinocyte
cell membranes binds specific anti SSA antibody, inducing cytotoxic damage
to keratinocytes by lumphocyte and monocyte effectors via ADCC.  The
variable involved in expression of SSA and SSB on keratinocyte cell
membranes will be tested and the binding of antibodies to SSA and SSB to
purified antigenic components and to the molecular complex containing both
antigens will be analyzed.  Using this information, anti SSA and anti SSB
dependent keratinocyte lysis will be analyzed in vitro and in vivo in
different models using cultured human keratinocytes as target, human skin
explants as targets, human skin grafted onto the nude mouse as a target, or
guinea pig skin as a target.  Relevant models of keratinocyte damage by
anti SSA will be used to test the mechanisms of action of corticosteroids,
antimalarials, dapsone, retinoids, antimetabolits, and antioxidants as
useful or potentially useful drugs in the treatment of cutaneous lupus.

Another important set of aims of this project involves the study of the
variable susceptibility to cytotoxicity of different cutaneous targets
(keratinocyts, melanocytes, endothelial cells, fibroblasts).  This portion
of the study will focus on antioxidant defenses of cutaneous targets, how
differences in these affect the susceptibility of these cells to
immunologic lysis and how therapeutic antioxidants may affect these targets
in skin disease.

Finally, we will begin pilot projects to study antibody dependent
cytotoxicity in other skin diseases such as pemphigus vulgaris, bullous
pemphigoid, alopecia areata, and vitiligo.

## Key facts

- **NIH application ID:** 3155409
- **Project number:** 5R01AR026427-09
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **SAM.gov UEI:** MW8JHK6ZYEX8
- **Principal Investigator:** DAVID A. NORRIS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1988
- **Award amount:** $164,401
- **Award type:** 5
- **Project period:** 1980-01-01 → 1991-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3155409

## Citation

> US National Institutes of Health, RePORTER application 3155409, CYTOTOXIC MECHANISMS IN CUTANEOUS DISEASE (5R01AR026427-09). Retrieved via MORVS 2026-10-24 from https://api.morvs.ai/grant/nih/3155409. Licensed CC0.

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