Normal pregnancy represents a state of maternal tolerance to an antigenically disparate fetus. Some patients with recurrent spontaneous abortions are believed to lose the embryo through mechanisms involving immunologic rejection. Blocking factors have been described in the sera of normal pregnant women that may modulate the maternal immune response, preventing embryonic rejection during pregnancy. The mechanism by which they exert this effect is unknown. Pregnancy may induce unresponsiveness to the fetal allograft by the induction of antiidiotypic antibodies that, in turn, regulate the immune response at a cellular level. Such tolerance induction is similar to the situation encountered in renal transplantation, in which pre-transplant blood transfusions (BT) have a beneficial effect on graft survival. Preliminary data generated in our lab indicate that post-BT patients generate anti-HLA antiidiotypic antibodies which may be important in engendering allograft tolerance. We propose to investigate the sera of normal pregnant women and of patients with recurrent spontaneous abortion for evidence of anti-HLA antiidiotypic antibodies using enzyme immunoassay (EIA) techniques developed in our laboratory. We will isolate these factors by affinity chromotography techniques and study their effect on total IgG, IgM and specific anti-HLA IgG and IgM production by maternal control, and habitual abortion patient-derived isolated cultured lymphocytes in vitro. Using cultured lymphocytes we will study the in vitro effect of soluble HLA-Ag and HLA/anti-HLA immune complexes on total IgG, IgM and specific anti-HLA IgG, IgM production. It is anticipated that these experiments will provide data on mechanisms responsible for normal maternal-fetal tolerance and fetal rejection. The information obtained from these studies may be of help to design studies involving immunization to obtain active suppression of anti-HLA responses.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Unknown (R23)
Project #
5R23HD019784-02
Application #
3448108
Study Section
Human Embryology and Development Subcommittee 2 (HED)
Project Start
1985-01-01
Project End
1986-06-30
Budget Start
1986-01-01
Budget End
1986-06-30
Support Year
2
Fiscal Year
1986
Total Cost
Indirect Cost
Name
University of California Los Angeles
Department
Type
Schools of Medicine
DUNS #
119132785
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Barkley, S C; Sakai, R S; Ettenger, R B et al. (1987) Determination of antiidiotypic antibodies to anti-HLA IgG following blood transfusions. Transplantation 44:30-4