# MECHANISMS OF AUTOREACTIVITY IN SLE

> **NIH NIH R01** · UNIV OF NORTH CAROLINA CHAPEL HILL · 1990 · $194,483

## Abstract

Anti-Sm antibodies are a highly specific marker for the diagnosis of SLE in
humans and in certain SLE mouse strains.  The expression of these
autoantibodies is under genetic control in mice, although the nature of
this control is not at present understood.  In addition, the expression of
anti-Sm antibodies in a genetically predisposed mouse depends on stochastic
processes.  The current studies are organized around the working hypothesis
that the initiation of the anti-Sm response in individually genetically
predisposed animals results from the rearrangement or somatic mutation of
unique variable region genes (either light chain or heavy chain).  Once the
response is initiated, it is amplified by an (?abnormal) antibody-mediated
positive feedback mechanism which results in an enhancement of the response
and a diversification, either through somatic mutation or through the
recruitment of new clones.  The genetic predisposition to the anti-Sm
response probably relates to a susceptibility to severe SLE, even through
the antibody itself is not directly pathogenic.  In the current proposal,
we will investigate the genetics of the anti-Sm response by crossing
anti-Sm positive and anti-Sm negative SLE mouse strains.  We will breed
anti-Sm positive and anti-Sm negative congenic mouse strains.  We will
compare the spontaneous anti-Sm response to the passive antibody-induced
anti-Sm response, as well as to anti-Sm response induced by the injection
of purified Sm in adjuvant.  We will also investigate the control of
expression of the anti-Sm trait in genetically predisposed strains by
determining the repertoire of immunoglobulin variable region genes utilized
in this response, and the role that somatic mutation plays.  We will look
at the expression of anti-Sm antibodies in allotype heterozygous animals in
order to determine clonality of the anti-Sm response and changes in
clonality over time.  Finally, we will study an unusual system of positive
feedback caused by passive administration of anti-Sm antibody, which may be
important in the development of the high titer anti-Sm response seen in
individual positive animals.

## Key facts

- **NIH application ID:** 3155432
- **Project number:** 5R01AR026574-10
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **SAM.gov UEI:** D3LHU66KBLD5
- **Principal Investigator:** ROBERT A. EISENBERG
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1990
- **Award amount:** $194,483
- **Award type:** 5
- **Project period:** 1979-12-01 → 1992-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3155432

## Citation

> US National Institutes of Health, RePORTER application 3155432, MECHANISMS OF AUTOREACTIVITY IN SLE (5R01AR026574-10). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3155432. Licensed CC0.

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