Mechanisms of erythrocyte antibody-mediated immune suppression

Anti-D (also known as RhIg) is a human-derived antibody specific for the erythrocyte RhD antigen which is currently used to prevent hemolytic disease of the fetus and newborn by a process known as antibody-mediated immune suppression (AMIS). Anti-D is injected into a very vulnerable segment of the population (expectant mothers) and there is concern for its potential to one day harbor an emerging pathogen. It is desirable to replace the current donor-derived product with a monoclonal antibody, however the mechanism(s) of AMIS remain unsolved. A hypothesis of AMIS is antigen-loss whereby anti-D results in the removal of the RhD antigen from the erythrocyte. The objective of this grant is to move towards replacing anti-D with a monoclonal anti-D antibody. This grant application will first test the hypothesis that antigen-loss works in mice, followed by test tube studies (in vitro studies) to see if the same process occurs in the test tube. Following this we will perform in vitro studies using several human monoclonal anti-D antibodies. This research will provide important information to inform the development of a potential monoclonal anti-D substitute. This project is aimed at the Canadian Blood Services research priority; replacing or improving blood products through new therapies or technologies.

LAZARUS, Alan

Canadian Blood Services

Intramural Research Grant Program

Ontario

$400,000