Detection of antitrophoblast antibodies in the sera of patients with anticardiolipin antibodies and fetal loss.
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.
McCrae
K R
KR
Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia.
DeMichele
A M
AM
Pandhi
P
P
Balsai
M J
MJ
Samuels
P
P
Graham
C
C
Lala
P K
PK
Cines
D B
DB
D000022:Abortion, Spontaneous / Q000209:etiology*; D017153:Antibodies, Anticardiolipin / Q000097:blood*; D017152:Antibodies, Antiphospholipid / Q000097:blood; D001323:Autoantibodies / Q000097:blood*; D000939:Epitopes; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007132:Immunoglobulin Isotypes / Q000097:blood; D066298:In Vitro Techniques; D011247:Pregnancy; D011994:Recombinant Proteins / Q000378:metabolism; D013928:Thromboxane A2 / Q000096:biosynthesis; D014327:Trophoblasts / Q000276:immunology* / Q000502:physiology; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism
D017153:Antibodies, Anticardiolipin; D017152:Antibodies, Antiphospholipid; D001323:Autoantibodies; D000939:Epitopes; D007074:Immunoglobulin G; D007132:Immunoglobulin Isotypes; D011994:Recombinant Proteins; D013928:Thromboxane A2; D014568:Urokinase-Type Plasminogen Activator; C067551:saruplase