One of the major neonatal defenses against bacterial and viral infection is maternally-derived IgG. Low levels of transplacentally-acquired IgG may be a contributing factor in the increased susceptibility of premature neonates to infection. In addition to the transient protection afforded by antibody against potentially infectious agents, passively acquired anti-idiotypic antibody can alter the development of active immunity in the neonate. In certain situations passively acquired antibody may not be desirable. Antibody acquired in utero from diseased mothers may interfere with early serodiagnosis of the disease in the neonate. Passively acquired antibody from mothers with certain autoimmune diseases not only hinder serodiagnosis but may also induce a transient form of the disease in the neonate. The long term goal of the proposed study is to establish more reliable methods for early serodiagnosis of disease in the neonate and to develop strategies that will enhance neonatal resistance to disease by regulating transplacental passage of selected antibody specificities in utero. Proposed models of IgG transport to the fetus involve binding to Fc receptors on placental tissues followed by endocytosis of the receptor-ligand complex and transport across the cell where IgG is released into the fetal circulation. Numerous studies suggest that within an IgG subclass transport rates vary considerable among different individuals and that within an individual there is selective transfer of different antibody specificities. The hypothesis to be tested in this proposal is that transport of antibody to the fetus occurs by a mechanism that can preferentially select antibodies based on their antigenic specificity or other idiotypic characteristics. This mode of selection would be influenced by specific immune complexes that exist during normal immune responses. To address this hypothesis transport of monoclonal antibodies that have defined antigenic and idiotypic specificities will be used.
The specific aims of this proposal are: 1) To determine what modification if any occurs to an IgG molecule as it crosses the placenta; 2) To assess the effect of antigen/antibody or idiotype/anti-idiotype immune complexes on the rate of transfer of a monoclonal antibody across the placenta; and 3) To determine the effect of maternal immune status on transplacental passage of antibodies. These studies will provide insight into the mechanisms of transplacental passage of antibodies, the identification of maternal antibody clonotypes in fetal serum, and ways by which the maternal immune system might be manipulated to enhance neonatal resistance to infection.
|Oritani, Kenji; Hirota, Seiichi; Nakagawa, Taishirou et al. (2003) T lymphocytes constitutively produce an interferonlike cytokine limitin characterized as a heat- and acid-stable and heparin-binding glycoprotein. Blood 101:178-85|