Page 550 - Review of Medical Microbiology and Immunology ( PDFDrive )

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CHAPTER 62 Major Histocompatibility Complex & Transplantation
HLA Typing in the Laboratory
ling to be BD (i.e., a zero-haplotype match).
Prior to transplantation surgery, laboratory tests, com-
monly called HLA typing or tissue typing, are performed
The Fetus Is an Allograft That
to determine the closest MHC match between the donor
Is Not Rejected
and the recipient.
There are two methods commonly used in the labora-
tory to determine the haplotype (i.e., the class I and class II
foreign to the mother, yet allograft rejection of the fetus
alleles on both chromosomes) of both the potential donors
does not occur. This is true despite many pregnancies from
and the recipient. One method is DNA sequencing using A fetus has MHC genes inherited from the father that are
the same mother–father combination that produce off-
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polymerase chain reaction (PCR) amplification and spe-
spring with the same MHC haplotypes. The reason that the
cific probes to detect the different alleles. This method is
mother fails to reject the fetus is unclear. The mother forms
highly specific and sensitive and is the method of choice
when available. The other method is serologic assays, in
therefore, the reason is not that the mother is not exposed
which cells from the donor and recipient are reacted with a
to fetal antigens. One possible explanation is that the
battery of antibodies, each one of which is specific for a
trophoblast layer of the placenta does not allow maternal
different class I and class II protein. Complement is then
T cells to enter the fetus.
added, and any cell bearing an MHC protein homologous
to the known antibody will lyse. This method is satisfactory
Results of Organ Transplants
in most instances but has failed to identify certain alleles
that have been detected by DNA sequencing.
lymphocyte culture and histocompatibility antigen typing,
If sufficient data cannot be obtained by DNA sequenc-
the long-term survival of a transplanted organ or tissue is
ing or serologic assays, then additional information regard- If the donor and recipient are well-matched by mixed-
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enhanced. Also, long-term survival is better if the donor is
ing the compatibility of the class II MHC proteins can be
living rather than deceased. In 2010, the 5-year survival
determined by using the mixed lymphocyte culture
rate of kidney transplants from living donors, who are often
(MLC) technique. This test is also known as the mixed
lymphocyte reaction (MLR). In this test, “stimulator” lym-
recipient, is approximately 90%, whereas the 5-year sur-
phocytes from a potential donor are first killed by irradia-
vival rate of kidney transplants from deceased donors (i.e.,
tion and then mixed with live “responder” lymphocytes
a zero-haplotype match) is approximately 80%. The 5-year
from the recipient; the mixture is incubated in cell culture
survival rate of heart transplants that are from deceased
to permit DNA synthesis, which is measured by incorpora-
donors (i.e., a zero-haplotype match) is approximately 75%.
tion of tritiated thymidine. The greater the amount of DNA
Corneal transplants have a very high rate of success for a
synthesis in the responder cells, the more foreign are the
class II MHC proteins of the donor cells. A large amount of
the lymphatic supply of the eye prevents many antigens
DNA synthesis indicates an unsatisfactory “match” (i.e.,
from triggering an immune response. Because corneal
donor and recipient class II [HLA-D] MHC proteins are different reason, namely, because corneas are avascular and
transplants elicit a weak rejection response, immunosup-
not similar and the graft is likely to be rejected). Therefore,
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pression is usually minimal. In contrast, most other trans-
the best donor is the person whose cells stimulated the
plants require long-term immunosuppression, although
incorporation of the least amount of tritiated thymidine in
the recipient cells.
with time, and in some recipients, a state of tolerance
In addition to the tests used for matching, preformed
ensues and the drugs can be stopped.
cytotoxic antibodies in the recipient’s serum reactive
against the graft are detected by observing the lysis of
Graft-Versus-Host Reaction
donor lymphocytes by the recipient’s serum plus comple-
ment. This is called cross-matching and is done to prevent
Well-matched transplants of bone marrow may establish
hyperacute rejections from occurring. The donor and
recipient are also matched for the compatibility of their
graft-versus-host (GVH) reaction develops in about two-
ABO blood groups. The laboratory tests used to determine
2
thirds of the recipients.
ABO blood groups are described in Chapter 64. themselves initially in 85% of recipients, but subsequently a
This reaction occurs because grafted immunocompe-
Among siblings in a single family, there is a 25% chance
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tent T cells proliferate in the irradiated, immunocompro-
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for both haplotypes to be shared, a 50% chance for one
mised host and reject host cells with “foreign” proteins,
haplotype to be shared, and a 25% chance for no haplotypes
to be shared. For example, if the father is haplotype AB, the
mother is CD, and the recipient child is AC, there is a 25%
GVH reactions can also occur in immunodeficient patients given a
chance for a sibling to be AC (i.e., a two-haplotype
match), a 50% chance for a sibling to be either BC or AD
donor’s blood that react against the recipient’s cells.
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