An immunological mechanism called thrombocytosis could explain the effectiveness of Rh immunoglobulin (RHIG) preventive therapy for hemolytic disease of the fetus and newborn (HDFN), according to a published study in Immunobiology and Immunotherapy.
Blood types are defined by certain molecules (antigens) present in the membrane of red blood cells. Some examples of these antigens are the A, B, and Rh antigens, which are present in some persons and absent in others.
HDFN is characterized by the destruction of fetal red blood cells (RBCs) by maternal antibodies in pregnancies where the fetus has a different blood type than the mother. These antibodies are produced after the mother’s immune system enters into contact with the antigens present in the membrane of fetal RBCs in previous pregnancies.
What is HDFN?
Hemolytic disease of the fetus and newborn (HDFN) is an immune-mediated red blood cell (RBC) disorder that occurs when a baby’s RBCs break down quickly, which is called hemolysis. HDFN is caused by a mismatch between a mother’s and her baby’s blood type (A, B, AB, or O) or Rhesus (Rh) factor (Rh-positive or Rh-negative) during pregnancy. Numerous antibodies to RBC antigens can be linked to HDFN, such as those from the ABO and Rh blood group systems.
For decades, HDFN due to Rh antigen incompatibility has been prevented by administration of RHIG immunoglobulin after a first pregnancy, this prevents the production of the antibodies that could cause HDFN in subsequent pregnancies. However, the mechanism by which RHIG prevents antibody formation has not been fully established.
Learn more about HDFN therapies
Some studies suggest that RHIG administration could lead to antigen loss in the membrane of RBCs. This antigen loss could be mediated by a mechanism called trogocytosis, which involves transferring membrane fragments from one cell to another. The authors aimed to confirm this hypothesis through experiments performed in mice models.
The authors observed that antibodies capable of inducing immune suppression caused a loss in surface antigens. Still, the loss of these antigens was accompanied by a membrane loss, which supports trogocytosis as a potential factor contributing to RHIG efficacy.
“In summary, our research elucidates the pivotal role of trogocytosis in antigen loss mediated by AMIS antibodies. These insights recommend that in the design of anti-D monoclonals for prophylactic use, the capacity to induce trogocytosis-driven antigen loss should be a key consideration,” the authors wrote.
