IMMUNIZATION OF RHESUS IMMUNIZATION: THE PROSPECT OF A MONOCLONAL IMMUNOGLOBULIN TO PREVENT HAEMOLYTIC DISEASE OF THE NEWBORN
Anti-Rhesus (D) immunoglobulin is the only drug that selectively blocks an unwanted immune response to a specific antigen. Due to the development of this unique drug, it has become possible to prevent the immunization of D-negative women with D-positive fetus/ newborn erythrocytes and dramatically reduce the frequency of hemolytic disease - a severe fetal pathology caused by the mother's immune antibodies. Anti-D immunoglobulin, which is obtained from the sera of immune donors, has been used in clinical practice for about 50 years, but the exact mechanism of action of the drug is not clear until now. The study of the properties and mechanism of the action of anti-D immunoglobulin, as well as attempts to create a monoclonal analogue, put before the researchers a lot of questions that go far beyond a narrow clinical topic. The review considers possible mechanisms of immunosuppressive action of anti-D immunoglobulin: antigen masking; rapid destruction of D-positive erythrocytes by anti-D antibodies; elimination of antigen-specific clones of B cells. The reasons why it was not possible to create an effective monoclonal preparation, the protective properties of which are not inferior to the serum analogue, are considered. The biochemical and effector properties of serum anti-D immunoglobulin indicate that the fraction of anti-D antibodies with a unique glycosylation pattern can respond to the immunosuppressive effect. The effect on the glycan structure allows controlling the effector properties of monoclonal antibodies and conferring a high affinity for the FcγRIII receptor, which is involved in the rapid excretion of D-positive red blood cells from the bloodstream. The review contains data from our own research in the field.