# RENAL DISEASE OF SYSTEMIC LUPUS

> **NIH NIH R01** · UNIVERSITY OF WASHINGTON · 1993 · $294,728

## Abstract

DESCRIPTION (Adapted from Applicant's Abstract):The proposed studies are
directed at clarifying the pathogenic mechanisms of the renal disease of
systemic lupus erythematosus (SLE).

Previous studies identified in patients with proliferative lupus
glomerulonephritis a new set of autoantibodies, directed to the collagen-
like region (CLR) of C1q molecules, a component of the complement system.
These antibodies may prolong the persistence of immune deposits in
glomeruli and alter their location.  An experimental model in mice will
be employed to determine if the antibodies to CLR will alter the fate of
immune complexes in glomeruli.

In patients with SLE a large number of autoantibodies exist in
circulation. It is not known which of these antibodies, in addition to
antibodies to DNA, contribute to the renal disease.  Improved methods for
recovery of antibodies from renal glomeruli will be evaluated using
experimental models. With these methods antibodies will be recovered from
glomeruli of patients who have died with SLE and the recovered antibodies
will be characterized.

Some evidence exists for the formation of covalent bonds between immune
deposits and structural molecules of the glomerular basement membrane.
The presence of covalent bonds will be established and the basement
membrane molecules bound to immune reactants will be identified.
Covalent binding of immune deposits to glomerular structures may be an
important mechanism for prolonging their presence in kidneys. Studies
will be conducted on the role of mononucleosomes in the formation of
glomerular immune deposits. Nucleosomes will be prepared, radiolabeled,
injected into mice and localization in glomeruli will be assessed.  Once
mononucleosomes deposit in glomeruli, antibodies to histones and
antibodies to DNA will be injected to determine the extent and location
of immune complex formation.

The completion of these investigations should substantially enhance our
knowledge of the pathogenic mechanisms in renal disease of patients with
SLE.

## Key facts

- **NIH application ID:** 3154745
- **Project number:** 2R01AR011476-25A1
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **SAM.gov UEI:** HD1WMN6945W6
- **Principal Investigator:** MART MANNIK
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $294,728
- **Award type:** 2
- **Project period:** 1976-06-25 → 1996-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3154745

## Citation

> US National Institutes of Health, RePORTER application 3154745, RENAL DISEASE OF SYSTEMIC LUPUS (2R01AR011476-25A1). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3154745. Licensed CC0.

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