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Pregnancy Related Transfusion ImmunologyABO Compatibility Project, IRB # i037902

Jill Seaman, MS II

Michigan State University, College of Human Medicine

PREGNANCY AND

FETO-MATERNAL ALLOIMMUNIZATION

TREATMENTRH ANTIGEN

REFERENCES

OVERVIEW

CONTACT

Jill Seaman

ABO Compatibility Project

Email: seamanji@msu.edu

Each parent donates twenty three

chromosomes so that at

conception a fetus receives a

polymorphic set of antigenic

information from each parent.

http://www.post-gazette.com/genome/diseases.asp

Chromosome map

The genetic information comes

together forming a forty six

chromosome, genetically unique

individual that is hosted by the

mother much like an allograft, or

parasite.

http://www.mathemagic.org/MOBM/DynamicDNA.html

Karyotype

This means that the fetus has

different tissue antigens from its

host mother, and the mother

could potentially respond to the

paternal tissue antigens after

implantation causing fetal

rejection.

The Rh system was discovered in the 1940s by Karl

Landsteiner through his work on Rhesus monkeys.

Rh is known to have over fifty different antigens, which

bind the cytoskeleton providing structure to the erythrocyte

membrane. Sensitization to the Rh antigen, especially the

D antigen, is the most common cause of hemolytic

disease3.

Maternal response to Rh is due to sensitization from a

previous exposure, either from past blood transfusions or

a prior pregnancy where there was exposure to the fetal

blood2.

Concurrent ABO incompatibility has a protective effect on

immunization to RhD3, this is a result of the anti-A or anti-

B IgM antibodies (which cannot cross the placenta)

coating and removing them from maternal circulation4.

Mothers who are Rh- and deliver Rh+ babies are at

risk of developing anti-Rh antibodies. Treatment is

necessary to prevent future Rh+ babies from

developing hemolytic disease; without this

preventative measure 14% of women will generate

anti-RhD antibodies within six months of delivery or

during their next pregnancy5.

Over the past thirty years it has been known that

passive immunization with anti-Rh (anti-D) IgG can

prevent adverse reactions in subsequent

pregnancies, so all Rh+ women giving birth to Rh-

babies are prophylactically treated with 100-300 µg

of anti-D gamma globulin (Rhogam) at 28 weeks4

and within 72 hours of delivery5.

Incidence of immune hydrops and erythroblastosis

fetalis have decreased significantly in urban areas4.

Today, nearly all Rh hemolytic disease is considered

preventable5.

Feto-maternal alloimmunization is the presence of

antibodies in a pregnant mother directed at paternal

antigens in the red blood cells of the fetus, typically

as the result of previous sensitization. Transfer of

fetal antigens into the maternal bloodstream via the

placenta can result in hemolysis in the fetus and

newborn2. This can present clinically in different

forms ranging from a mild anemia with

hyperbilirubinemia to severe fetal jaundice and even

death of the fetus (hydrops fetalis and

erythroblastosis fetalis). This reaction is known as

hemolytic disease of the newborn3.

Initial exposure to fetal antigen elicits an IgM

antibody response which cannot cross the placental

barrier, so the first pregnancy doesn’t typically exhibit

hemolytic disease. On second exposure the

maternal antibody response is IgG, which can cross

the placenta causing harm to the fetus4.

Mismatches between maternal and paternal genes

include not only the ABO blood typing, but also the

Rh antigen complex.

1. Mellor, A.L. and D. H. Munn. “Immunology at the Maternal-fetal

interface: lessons for T cell Tolerance and Suppression.” Annu Rev

Immunol. 18 (2000): 367-391.

2. Bricca, P., E. Guinchard and C. Guitton Bliem. “Management of

feto-maternal red cell alloimmunizations.” Transfus Clin Biol. 18.2

(2011):269-276.

3. Westhoff, Connie M. “The structure and Function of the Rh antigen

Complex.” Semin Hematol. 44.1 (2007):42-50.

4. Kumar et al. Robbins and Cotran: Pathological Basis of disease.

8th ed. Philadelphia: Saunders Elsevier, 2010.

5. Zipursky, Alvin and Vinod K. Paul. “The global burden of Rh

disease.” Arch Dis Child Fetal Neonatal. 96.2 (2011):F84-F85.Development of erythroblastosis fetalis (hemolytic disease of the newborn) caused

when an Rh- mother carries and Rh+ fetus (left), and effect of treatment with anti-Rh

antibody, Rhogam (right)

With fertilization and

implantation, the embryo

becomes an allograft, utilizing

the maternal blood supply. The

disparity between tissue

antigens in the embryo and

host may cause the mother to

have an immune response1.http://www.sciencephoto.com

http://www.neuropathologyweb.org/chapter3/chapter3eBilirubinencephalopathy.html

Kernicterus.

Maternal gamma globulin antibodies cross the placenta

causing destruction of the fetal red cells. Unconjugated

bilirubin from the hemolytic reaction can cross the poorly

developed blood-brain barrier of the fetus and bind to lipids in

the central nervous system. This accumulation causes severe

neurologic damage, the most serious threat in fetal hydrops,

known as kernicterus4.

SEM of sperm entering egg

Rhesus Monkeys

http://www.sciencephoto.com

http://wenliang.myweb.uga.edu/mystudy/immunology/ScienceOfImmunology/Hypersensitivitydiseases.html

http://www.umm.edu/pregnancy/000203.htm

Rh- Maternal response to Rh+ fetus,

preventable through the use of Rhogam