# HOST DEFENSES IN SYSTEMIC LUPUS ERYTHEMATOSUS

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 1990 · $142,995

## Abstract

One objective of the proposed research is to examine the interaction
between vitamin D-binding protein (i.e., Gc globulin, DBP), the
complement (C5)-derived peptide, C5a des Arg, and the Bb fragment of
complement factor B. We have established that DBP is the putative C5a des
Arg cochemotaxin and that a Bb-like peptide is the inhibitor of
complement (C5)-derived chemotactic activity present in serum (and
plasma) from some patients with active systemic lupus erythematosus
(SLE). DBP forms a complex with C5a des Arg by attaching to sialic acid
residues within the oligosaccharide portion of C5a des Arg, while Bb
blocks the interaction between DBP and C5a des Arg. The complete sequence
of DBP and Bb are known, and both isoforms of DBP (Gc1 and Gc2) have been
cloned. We will test DBP isoforms for biologic activity and will generate
fragments of DBP and Bb by enzymatic digestion. Fragments of DBP and Bb
exhibiting biologic activity will be sequenced to determine specific
sites involved in their interactions. Partial (and known) sequences of
DBP and Bp will be used to generate synthetic oligonucleotide probes
containing all possible substitutions at each codon. These
oligonucleotides will be used to amplify relevant fragments of human,
rabbit and porcine liver cDNA using the polymerase chain reaction, which
will be used in an expression system to generate specific peptides to be
tested for biologic activity. Mutants of biologically active peptides,
derived from DBP and Bb cDNAa, will be generated to determine specific
sites involved in the interaction between DBP, Bb and native C5a des Arg
and human polymorphonuclear leukocytes (PMN). Preliminary experiments
have demonstrated the radiolabeled BP binds to PMN in a saturable
fashion. Experiments will be performed to determine the binding site for
DBP on PMN as well as the specific site within /dBP involved in its
binding to PMN. Also, we will examine the effect of DBP on the binding to
PMN of biologically active, radiolabeled C5a des Arg and on C5a des Arg-
induced events involved in PMN activation. The studies out lined in this
proposal should yield new information that may explain (in part) why
patients with SLE have an increased susceptibility to severe bacterial
infections. On a more basic level, these studies should provide
information concerning structure-activity relationships and mechanism
involved in regulating the biologic activities of complement-derived
peptides.

## Key facts

- **NIH application ID:** 3155680
- **Project number:** 5R01AR028566-11
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **SAM.gov UEI:** KMH5K9V7S518
- **Principal Investigator:** H D PEREZ
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1990
- **Award amount:** $142,995
- **Award type:** 5
- **Project period:** 1980-09-01 → 1992-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3155680

## Citation

> US National Institutes of Health, RePORTER application 3155680, HOST DEFENSES IN SYSTEMIC LUPUS ERYTHEMATOSUS (5R01AR028566-11). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3155680. Licensed CC0.

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