Our working hypothesis is that antiphospholipid antibodies, especially antiphosphatidlyserine, are responsible for many of the symptoms of early and severe pregnancy-induced hypertension (PIH) and may contribute to milder forms. Very high levels of antiphospholipid antibodies lead to pregnancy loss before the hypertension can develop whereas lower levels result in a live birth complicated by severe and early hypertension, thrombosis, thrombocytopenia (with elevated antiplatelet antibody levels), severe intrauterine growth retardation, and stroke. The mechanism of action for antiphospholipid antibody-induced PIH is through modulation of the relationship between platelets and vascular endothelial cells resulting in maternal and placental thrombosis and many of the symptoms of PIH. We will investigate the incidence of specificity of antiphospholipid antibodies from PIH patients using serologic reactivity in enzyme immunoassays, purify human polyclonal antibodies of known specificity and produce monoclonal human and mouse antiphospholipid antibodies, and study the effects of these antibodies on in vitro prostacyclin and thromboxane generation and on in vitro protein C activation. In addition, we will develop a rabbit model for antiphospholipid antibody-induced PIH.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD024490-04
Application #
3325106
Study Section
Special Emphasis Panel (SRC (MW))
Project Start
1988-08-10
Project End
1992-07-31
Budget Start
1991-08-01
Budget End
1992-07-31
Support Year
4
Fiscal Year
1991
Total Cost
Indirect Cost
Name
Wright State University
Department
Type
Schools of Medicine
DUNS #
City
Dayton
State
OH
Country
United States
Zip Code
45435
Rote, N S; Ng, A K; Dostal-Johnson, D A et al. (1993) Immunologic detection of phosphatidylserine externalization during thrombin-induced platelet activation. Clin Immunol Immunopathol 66:193-200
Lyden, T W; Ng, A K; Rote, N S (1993) Modulation of phosphatidylserine epitope expression by BeWo cells during forskolin treatment. Placenta 14:177-86
Lyden, T W; Vogt, E; Ng, A K et al. (1992) Monoclonal antiphospholipid antibody reactivity against human placental trophoblast. J Reprod Immunol 22:1-14
Rote, N S; Walter, A; Lyden, T W (1992) Antiphospholipid antibodies--lobsters or red herrings? Am J Reprod Immunol 28:31-7
Haddow, J E; Rote, N S; Dostal-Johnson, D et al. (1991) Lack of an association between late fetal death and antiphospholipid antibody measurements in the second trimester. Am J Obstet Gynecol 165:1308-12
Carmody, M W; Ault, K A; Mitchell, J G et al. (1990) Production of monoclonal antibodies specific for platelet activation antigens and their use in evaluating platelet function. Hybridoma 9:631-41
Dostal-Johnson, D; Rote, N S; Branch, D W (1990) IgG1 and IgG2 are the predominant subclasses of antiphospholipid antibody in women with the lupus anticoagulant. Clin Immunol Immunopathol 54:309-19
Rote, N S; Dostal-Johnson, D; Branch, D W (1990) Antiphospholipid antibodies and recurrent pregnancy loss: correlation between the activated partial thromboplastin time and antibodies against phosphatidylserine and cardiolipin. Am J Obstet Gynecol 163:575-84
Rote, N S (1989) Pregnancy-associated immunological disorders. Curr Opin Immunol 1:1165-72