Detection of antitrophoblast antibodies in the sera of patients with anticardiolipin antibodies and fetal loss

Abstract

Women with anticardiolipin antibodies (ACLA) are at increased risk for fetal loss. One potential explanation for this outcome is that sera from these individuals contain antibodies reactive with trophoblast cells, which are involved in the establishment of the uteroplacental vasculature and maintenance of placental blood fluidity. To examine this hypothesis, we compared the incidence of trophoblast-reactive antibodies in 27 patients with ACLA and a history of fetal loss with that in 29 normal pregnant women. Sera from 20 patients, but only one control, contained trophoblast-reactive antibodies (P < .001). These antibodies were not directed against major histocompatibility class I antigens, and reacted with both term and first-trimester trophoblast cells. In most cases, sera from which ACLA were adsorbed by cardiolipin- containing liposomes maintained reactivity against cells. In addition, patient Ig fractions immunoprecipitated an approximately 62-kD protein from the trophoblast cell surface, stimulated the release of arachidonic acid and thromboxane A2 by trophoblasts, and inhibited the binding of prourokinase to trophoblast urokinase receptors. These observations show that sera from women with ACLA and a history of fetal loss contain antitrophoblast antibodies. These antibodies may be serologically distinct from ACLA, and may contribute to the pathogenesis of fetal demise.

Antiphospholipid Antibodies Alter Cell‐Death‐Regulating Lipid Metabolites in First and Third Trimester Human Placentae

“…As eicosanoids are lipids that elicit physiological responses at low concentrations, small fluxes in eicosanoid balance can have a profound effect on placental function . Over the past decade, several studies have shown that aPL disrupt production of eicosanoids, primarily prostacyclin and thromboxane A2, contributing to fetal loss, and this metabolomic analysis has identified a number of eicosanoid metabolites to add to the existing school of thought that aPL adversely affects placental eicosanoid production.…”

Pathophysiology of Antiphospholipid Syndrome

“…86 Further contributing to placental thrombosis is impairment of fibrinolysis by APA that inhibit the binding of prourokinase to its trophoblast receptor, and other antibodies that reduce factor XIIadependent profibrinolytic activity. 87,88 Anti-β 2-GPI antibodies target placental mitochondria, induce production of reactive oxygen species, release arachidonic acid and thromboxane A 2 , and bring about cellular damage. 89 They stimulate trophoblast IL-1β and VEGF secretion mediated by nucleotide-binding oligomerization domain-2 (NOD2), potentially accounting for the observed pro-inflammatory and angiogenic profile in patients with APA.…”

“…86 Further contributing to placental thrombosis is impairment of fibrinolysis by APAs that inhibit the binding of prourokinase to its trophoblast receptor, and other antibodies that reduce factor XIIa-dependent profibrinolytic activity. 87 88…”