Alloimmunization is an immune response where a person’s body produces antibodies against foreign antigens from another individual. These foreign antigens, recognized as “non-self,” can be introduced through events like blood transfusions, during pregnancy, or following organ transplantation.
How Alloimmunization Develops
The immune system’s primary function is to distinguish between “self” and “non-self” components within the body. When foreign antigens, which are unique proteins or markers, enter a person’s system, the immune system identifies them as invaders. This recognition triggers a complex series of events aimed at neutralizing or eliminating these foreign substances.
This process often involves specialized immune cells which engulf and break down the foreign antigens. These processed antigens are then presented to other immune cells, which become activated and orchestrate an immune response. This coordinated response includes the activation of cells leading to the production of specific antibodies, known as alloantibodies, against the foreign antigens.
Alloimmunization in Pregnancy and Its Effects
Red blood cell alloimmunization during pregnancy occurs when a pregnant individual’s immune system develops antibodies against antigens present on the fetal red blood cells, which were inherited from the father and are not present in the mother. The Rh (D) factor is the most recognized example of such an incompatibility. If an Rh-negative mother carries an Rh-positive baby, fetal red blood cells carrying the Rh (D) antigen can enter the mother’s bloodstream, typically during pregnancy or at delivery.
Upon exposure, the mother’s immune system recognizes these Rh (D) antigens as foreign and produces anti-D alloantibodies. While the first Rh-positive pregnancy may not be significantly affected, these antibodies persist. In subsequent Rh-positive pregnancies, these antibodies can cross the placenta and target the fetal red blood cells, leading to their destruction.
This destruction of fetal red blood cells results in a condition called Hemolytic Disease of the Fetus and Newborn (HDFN). The severity of HDFN can vary widely. Mild cases may present as mild anemia in the fetus, while more severe cases can lead to significant complications.
As fetal red blood cells are destroyed, the fetus may develop anemia, which can range from mild to severe. In severe cases, the fetus might develop hydrops fetalis, a life-threatening condition characterized by widespread fluid accumulation in various body tissues and cavities, including swelling under the skin or around internal organs, which can lead to heart failure and stillbirth if left untreated. After birth, the maternal antibodies can continue to destroy the infant’s red blood cells for up to 12 weeks, leading to delayed onset anemia. The breakdown of red blood cells releases bilirubin, which can accumulate in the newborn’s system, causing hyperbilirubinemia, or severe jaundice. This can result in yellowing of the skin and eyes, and if bilirubin levels become too high, it can lead to brain damage.
Diagnosis and Management
Diagnosing alloimmunization involves a series of screening and specific tests. An initial blood type and antibody screen are performed at the first prenatal visit for all pregnant individuals. This antibody screen helps detect the presence of clinically significant antibodies.
If antibodies are detected, further tests are conducted to identify the specific type of antibody and its concentration, known as the antibody titer. For pregnant individuals, monitoring the fetus for signs of anemia is done through specialized ultrasounds, which measure blood flow velocity in the fetal brain and correlate with the likelihood of anemia.
Management approaches depend on the severity of alloimmunization and the fetal condition. Close monitoring with regular antibody titers and ultrasound assessments is common for mild cases. If fetal anemia becomes severe, intrauterine transfusions may be performed, where red blood cells are directly injected into the fetal umbilical cord under ultrasound guidance. After birth, newborns with HDFN may receive phototherapy for jaundice, which uses light to break down bilirubin, or in more severe instances, exchange transfusions to replace the affected blood with compatible blood.
Preventing Alloimmunization
Preventing alloimmunization, particularly Rh (D) alloimmunization, has significantly reduced the incidence of HDFN. The primary method of prevention involves administering Rh immune globulin, also known as RhoGAM or anti-D immunoglobulin.
RhoGAM contains antibodies that bind to any Rh-positive fetal red blood cells that may have entered the Rh-negative mother’s bloodstream. This binding prevents the mother’s immune system from recognizing these foreign cells and producing her own anti-D antibodies.
This injection is typically given to Rh-negative mothers at approximately 28 weeks of gestation. An additional dose is administered within 72 hours after the birth of an Rh-positive baby, or after other events that could cause fetal-maternal bleeding, such as miscarriage, abortion, or certain invasive prenatal procedures like amniocentesis. While highly effective, prevention is not 100% guaranteed.