# FOURTH COMPLEMENT PROTEIN AND THE PATHOGENESIS OF SLE

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 1987 · $113,944

## Abstract

The goal of the research proposed here is to test the hypothesis that the
association between systemic lupus erythematosus and the A-null B1
phenotype of the fourth human complement protein (C4) is not fortuitous but
rather that it results from the relatively low covalent binding efficiency
of the C4B1 allotypic form of the protein to immune complexes composed of
nucleic acids and antibodies directed against them and that the poor
binding efficiency of the C4B1 allotype in serum could account, in part,
for the inefficient processing and clearance of the immune complexes via
C3b receptors of SLE patients of the C4 A-null B1 phenotype.

The experiments proposed here focus specifically on the chemistry of the
covalent binding properties of the A3 and B1 allotypes of C4 obtained from
normal, healthy donors and from donors with SLE.  In order to study the
covalent binding properties of these forms of C4 it is necessary to carry
out experiments under simple, chemically defined conditions.  The
fluid-phase binding system developed in this laboratory and a newly devised
solid-phase assay designed to take advantage of the binding of nucleic
acid-protein complexes to nitrocellulose filters will be used in the
research proposed here.  Both the fluid- and the solid-phase methods permit
the determination of the parameters that govern the covalent binding
reaction as well as the determination of the chemical nature of the bonds
that are formed.

Interactions between C4 and DNA and snRNP (ribonucleoprotein complexes of
nuclear origin) and immune complexes composed of DNA and snRNP and
antibodies will be investigated both in the completely defined fluid- and
solid-phase systems and in normal and patient sera.  A modified form of the
fluid-phase binding system will permit the study of the binding properties
of C4 of known allotypes in serum of both normal donors and those with
SLE.  These experiments with normal and patient sera will be the first time
that immune complexes relevant to SLE will have been studied from the point
of view of their interaction with the complement system.

The experiments proposed here are a direct test of the hypothesis that the
reactivity of C4 plays a role in the pathogenesis of SLE.  From their
results it will be possible to conclude whether or not the known
differences in the chemical reactivity of C4A3 and C4B1 are expressed in
their interactions with immune complexes of the sort that are found among
SLE patients.

## Key facts

- **NIH application ID:** 3157774
- **Project number:** 5R01AR036861-02
- **Recipient organization:** WASHINGTON UNIVERSITY
- **SAM.gov UEI:** L6NFUM28LQM5
- **Principal Investigator:** R P LEVINE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1987
- **Award amount:** $113,944
- **Award type:** 5
- **Project period:** 1986-04-01 → 1989-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3157774

## Citation

> US National Institutes of Health, RePORTER application 3157774, FOURTH COMPLEMENT PROTEIN AND THE PATHOGENESIS OF SLE (5R01AR036861-02). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3157774. Licensed CC0.

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