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Disorders in Immunity

Hemolytic Disease

Hemolytic disease of the newborn occurs when a mother has developed antibodies against antigens displayed on the surface of a fetus's red blood cells.

Hemolytic disease of the newborn (HDN) consists of lysis, or destruction, of fetal and newborn red blood cells that results from an influx of maternal antibodies into the fetus that target Rh antigens on the surface of the red blood cells. This occurs because of an incompatibility between the mother's Rh blood type and the fetus's Rh blood type. HDN, also called erythroblastosis fetalis, is commonly known as the "Rh-factor problem."

Antigens are substances that induce an immune response, and antibodies are the blood proteins produced to counteract a specific antigen. Blood is typed based on the presence or absence of surface antigens on red blood cells.

One group of antigen types forms the ABO blood groups. ABO blood grouping is the most common characterization of blood based on the presence or absence of A and B antigens on the surface of red blood cells. People have type A blood if their red blood cells have A antigens; those with type B blood have B antigens. People with type AB blood have A and B antigens, and if neither A nor B antigens are present, then the blood is type O. When receiving blood, it is important to know which type is being transfused so that the recipient does not experience adverse effects. Blood type O− is the universal donor because it has both A and B antigens on its red blood cells. Conversely, blood type AB is considered the universal receiver because it has both A and B antigens on its red blood cells. It can receive from an A, a B, an AB, or an O blood type person.

Blood Types in Humans

Blood Group
Antigens on Red Blood Cells A B A and B Neither A nor B
Antibodies in Blood Anti-B Anti-A Neither Anti-A nor Anti-B Anti-A and Anti-B

There are four main blood types in humans depending on the presence or absence of A and B antigens in the red blood cells and anti-A and anti-B antibodies in the plasma.

Another group of antigen types forms the Rh factor group. The Rh factor, also called the D antigen, is one of a group of antigens typically found on red blood cells. Individuals with the D antigens are classified as Rh+ (read as "positive"), and those without the D antigens are Rh- ("negative"). When a mother who is Rh- has a baby who is Rh+, the mother will develop immunoglobulin G (IgG) antibodies against her baby's D antigens. In future pregnancies there is the potential for HDN if she has a baby with antigens that match her IgG antibodies (in other words, another Rh+ baby). The IgG is able to cross the placenta and enter the fetus's circulation, where it binds to the antigens on red blood cells and mediates lysis. In these cases large numbers of fetal red blood cells are lysed and the child is born anemic or, in extreme cases, can die in utero. Newborns with HDN may exhibit a range of symptoms and may even appear healthy. IgG from the mother remains circulating in their blood, causing damage to red blood cells. The contents of lysed cells may build up in the brain, where they cause damage and lead to death.

Both ABO and Rh factor incompatibilities are examples of type II hypersensitivities. ABO incompatibilities are much more common than D antigen incompatibility, but fortunately IgG against A and B antigens rarely makes it to fetal circulation in sufficient quantities to cause HDN. Despite its rarity, HDN was once a regular cause of fetal and newborn death. Today, with regular, inexpensive, and easy blood typing, the disorder can be prevented. It is common treatment for Rh- mothers to receive medication (Rho immune globulin) that prevents activation of antibodies against the D antigen during pregnancy to guard against potential development of HDN. Similarly, Rh- mothers giving birth to their first Rh+ child are given medication after birth that removes D antigens from their blood so that they do not develop IgG antibodies in the first place.