# ANTIPHOSPHOLIPID ANTIBODY (PREGNANCY IN SLE)

> **NIH NIH R01** · HOSPITAL FOR SPECIAL SURGERY · 1992 · $47,751

## Abstract

Antiphospholipid antibody (aPL) is closely associated with recurrent
fetal death, thrombosis, and thrombocytopenia.  The mechanisms by which
the antibody causes the complications remain unexplained.  The specific
goals of this proposal are:

1.  To characterize the idiotypes of human polyclonal and mouse
monoclonal aPL antibodies and to define "pathogenic" public idiotypes.
Anti-id will also be used to detect aPL in the placenta and other
tissues by immunofluorescence.

2.  To define the pathophysiology aPL.  The effect of aPL on the
activity of the placental anticoagulant protein (PAP) will be analyzed
by ELISA as well as PL-dependent coagulation assays, KCT and APTT.  The
interaction of aPL with the lupus cofactor (apolipoprotein H) will be
evaluated by ELISA and KCT and APTT coagulation assays.  The levels of
cofactor in patients' sera will be determined by ELISA and the co factor
isoforms identified by isoelectric focusing.  Associations between PAP
levels, cofactor levels, cofactor isoforms and clinical complications
will be assessed.

3.  To explore the pathogenic nature of the antibody in spontaneous
(MRL/lpr) and induced mouse models.  Human polyclonal and mouse
monoclonal antibodies will be administered to normal pregnant mice, or
antiphospholipid antibodies will be induced in normal mice by
immunization with apolipoprotein H.  The effect on pregnancy (number of
pups) and hematology (platelets, thrombosis) will be determined.  To
suppress aPL production, anti-id antibodies will be administered to
MRL/lpr mice and circulating aPL levels, platelets and pregnancy outcome
monitored.

4.  To determine the VH sequences of aPL genes so as to define the
genetic origins of aPL in MRL mice.

The characterization and functional evaluation of PAP, lupus cofactor,
and anti-id antibodies will determine whether aPL antibodies are
directly involved in the pathogenesis of the syndrome and may uncover
their pathogenesis.  Identification of pathogenic idiotypes and the
genetic origin of aPL may provide tools to identify patients at risk.

## Key facts

- **NIH application ID:** 3156450
- **Project number:** 2R01AR032929-07A3
- **Recipient organization:** HOSPITAL FOR SPECIAL SURGERY
- **Principal Investigator:** AZZUDIN E GHARAVI
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1992
- **Award amount:** $47,751
- **Award type:** 2
- **Project period:** 1984-04-01 → 1993-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3156450

## Citation

> US National Institutes of Health, RePORTER application 3156450, ANTIPHOSPHOLIPID ANTIBODY (PREGNANCY IN SLE) (2R01AR032929-07A3). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3156450. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*