# ANTIPHOSPHOLIPID ANTIBODIES AND DISORDERS OF PREGNANCY

> **NIH NIH R01** · WRIGHT STATE UNIVERSITY · 1994 · $193,317

## Abstract

Autoantibodies against acidic phospholipids (aPLs) are associated with
thrombosis and recurrent pregnancy loss.  Although aPLs are believed to
directly cause these disorders through inappropriate activation of clotting
this assumption is not clearly supported or refuted by any published data.
Likewise, there is considerable debate concerning the relevant
specificities of aPLs and their mechanisms of action, as well as why
individual patients, with apparently identical aPL specificities, present
with a large difference in symptoms.  Our central hypothesis is that aPLs
are directly responsible for pregnancy loss.  Our preliminary data would
further lead us to propose three testable specific hypotheses.  The first
is that aPLs are heterologous in specificity, the nature of which
determines the severity of the particular patient's clinical symptoms.  The
second hypothesis is that three cell types may be principal targets of
aPLs; the vascular endothelial cell, the platelet, and the trophoblast.
Which of these cells is primarily affected depends upon the collective
specificities of that particular patient's aPLs.  The third hypothesis is
that aPLs will directly induce reproductive failure in experimental
animals.  In order to test these hypotheses five specific aims have been
designed.  First, using monoclonal antibodies and purified antibodies from
patients we will evaluate the heterogeneity of aPLs through blocking
studies in ELISAs, adsorption with known phospholipids, reactivity with
artificial membranes, elution profiles on phospholipid affinity columns,
and comparison of represented idiotypes.  Second, we will investigate the
effects of aPLs on platelet activation.  Using flow cytometry and
monoclonal antibodies against platelet specific antigens and platelet
activation antigens, as well as in vitro measurement of thromboxane
production, we will measure the reactivity of aPLs on resting and activated
platelets, determine whether aPLs directly activate platelets or enhance
the response of platelets to other activators, and evaluate the level of
platelet activation in situ.  Third, we will evaluate the reactivity and
effects of aPLs on cultured bovine and human endothelial cells, including
their binding to resting and activated endothelial cells, their effect on
endothelial cell metabolism, and the characterization of endothelial cell
antigens reactive with aPLs.  Fourth, using placental preparations,
isolated cytotrophoblast, and a choriocarcinoma line, BeWo, we will
investigate the binding and effect of aPLs, including effects on in vitro
cytotrophoblast intercellular fusion and overall metabolic activity.
Fifth, using pregnant mice and guinea pigs we will test the direct
biological effects of aPLs on pregnancy loss.  The product of this study
will be an in vitro and in vivo analysis of aPL specificity and function in
relationship to pregnancy loss.

## Key facts

- **NIH application ID:** 2198930
- **Project number:** 5R01HD023697-07
- **Recipient organization:** WRIGHT STATE UNIVERSITY
- **SAM.gov UEI:** NPT2UNTNHJZ1
- **Principal Investigator:** NEAL STEWART ROTE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1994
- **Award amount:** $193,317
- **Award type:** 5
- **Project period:** 1988-08-01 → 1996-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/2198930

## Citation

> US National Institutes of Health, RePORTER application 2198930, ANTIPHOSPHOLIPID ANTIBODIES AND DISORDERS OF PREGNANCY (5R01HD023697-07). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/2198930. Licensed CC0.

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