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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: [email protected]
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