# TISSUE INJURY MECHANISMS - SYSTEMIC LUPUS ERYTHEMATOSUS

> **NIH NIH R01** · HAHNEMANN UNIVERSITY · 1989 · $410,002

## Abstract

The major objective of the proposed experiments is to clarify mechanisms of
tissue injury which result from deposition of antigen-antibody complexes.
Systemic lupus erythematosus (SLE) is a prototype model for the study of
immune complex disease in man.  Antigen-antibody complexes derived from the
circulation as well as complexes formed in situ appear to be of
pathogenetic importance.  Prior studies indicate that the
polynucleotide-anti-polynucleotide system is of primary importance.  To
further define these complexes, the specificity and relative antigen
avidity of anti-polynucleotide antibodies will be studied, and
polynucleotide backbone epitopes will be defined.  The cytotoxic potential
of in situ complexes formed between DNA denatured by UV light or damaged
cell nuclei and anti-polynucleotide antibodies will be evaluated.  Studies
concerning the role of autoantibodies to glomerular and cutaneous basement
membrane will be continued to assess the contribution of auto-immune
reactions in SLE and related diseases.  The complement system mediates
inflammatory lesions, following activation of Clg-globulin, by a series of
enzyme reactions which modulate formation of peptide fragments,
intermediate complexes and the membrane attack complex (MAC).
Ultrastructural localization of the MAC and immunochemical studies of
neoantigen determinants will be performed to characterize terminal
complement complexes, factors which initiate classical or alternative
pathway activation and the pathogenetic importance of membranolysis.
Depletion of terminal complement components in experimental immune disease
to inhibit assembly of the MAC is also planned to determine if the failure
to form this complex affects inflammation and membrane injury.  The
following reagents and techniques will be utilized for the performance of
these studies:  monoclonal antibodies to polynucleotides and complement
proteins; rabbit antisera; immunofluorescence; immunoelectron microscopy;
hemolytic complement assays; and solid phase enzyme immuno-assays.

## Key facts

- **NIH application ID:** 3155215
- **Project number:** 5R01AR021715-13
- **Recipient organization:** HAHNEMANN UNIVERSITY
- **Principal Investigator:** DAVID KOFFLER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1989
- **Award amount:** $410,002
- **Award type:** 5
- **Project period:** 1975-01-01 → 1990-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3155215

## Citation

> US National Institutes of Health, RePORTER application 3155215, TISSUE INJURY MECHANISMS - SYSTEMIC LUPUS ERYTHEMATOSUS (5R01AR021715-13). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3155215. Licensed CC0.

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