Transcript Tissue typing (HLA Match) powerpoint

Tissue Typing
EVERYONE HAS SEVERAL ANTIGENS LOCATED
ON THE SURFACE OF HIS/HER LEUKOCYTES:
One
particular group of these
antigens is called the HLA
(Human Leukocyte Antigens).
THE HLA
Is
responsible for stimulating
the immune response to
recognize tissue as self versus
non-self.
Is
controlled by a set of genes
located next to each other on
chromosome 6 called the Major
Histocompatibility Complex
(MHC).
The
test that determines which
HLA antigens are present is called
tissue typing or HLA typing.
 Tissue
typing identifies the
similarity of the antigens present
in both the donor and the
recipient.


The closer the HLA antigens on the transplanted
organ match the recipient, the more likely that the
recipient’s body will not reject the transplant.
For this reason, tissue typing of the kidney donor and
recipient is necessary before a kidney transplantation.
THERE ARE TWO MAIN CLASSES OF
HLA ANTIGENS:

Class I (HLA-A, HLA-B, and HLA-Cw)

Class II (HLA-DR, HLA-DQ, and HLA-DP)
Every
person inherits each of
the following antigens from each
parent:






HLA-A antigen
HLA-B antigen
HLA-Cw antigen
HLA-DR antigen
HLA-DQ antigen and
HLA-DP antigen
The
set of HLA antigens
received from a parent is called
a haplotype.
 There
are a variety of alleles for
each of these HLA antigens.
 The
large number of possible
variations and combinations of
HLA antigens make finding a
match in a family more likely than
finding a match in the general
public.

When performing an HLA typing test for a
kidney transplant, the following HLA antigens
are looked at:
 HLA-A
 HLA-B
 HLA-DR

The MHC genes are the most polymorphic
known.

There are hundreds of known alleles for each HLA
Antigen.

Each allele is identified by a number (i.e. HLA-A1 or HLAA2).
 Six
HLA antigens are looked at for each
person.

Remember each person has two of each of the antigens (one
inherited from the mother and one inherited from the
father).

By analyzing which six of these HLA-antigens
both the donor and recipient have, scientists are
able to determine the closeness of tissue
matching.

A six-antigen match is the best compatibility between
a donor and recipient.

This match occurs 25% of the time between siblings who
have the same mother and father.
HLA TYPING TECHNIQUES
 Traditionally,
HLA typing was done using
serological techniques:

Blood from the patient was mixed with serum
containing known antibodies to determine
which antigens were present.
 HLA
typing now is predominantly done
using molecular techniques:



Patient’s DNA is isolated.
PCR is used to amplify specific HLA genes.
Genes are sequenced to determine which
alleles are present.

Once the donor and recipient have been tested for
tissue compatibility, the next step is an Antibody
Screening (also called a Panel Reactive Antibody
or PRA).

A small amount of the organ recipient’s serum is
mixed with cells from 60 different individuals (each
test is done separately).
PURPOSE OF ANTIBODY SCREENING

Scientists can determine how many different
HLA antibodies a patient has in his/her blood.
If a patient reacts with 30/60 cells, he/she is said to
have 50 Percent Reactive Antibody (also known as
PRA).
 The lower a person’s PRA, the less likely he/she is to
reject a transplant.

CROSSMATCH TEST

After tissue typing and antibody screening are
complete and a potential donor has been
identified, the final test is called a crossmatch
test.

Crossmatch Test: A small amount of the potential
donor’s white cells is mixed with a small amount of
the recipient’s serum.

By exposing the donor’s HLA to the recipient’s serum,
scientists can determine if the recipient has antibodies to
any of the donor’s HLA.
 Positive
Crossmatch: A reaction between
the donor’s and recipient’s samples occurs.
Indicates that the recipient’s body will likely
reject the implanted kidney.
 Indicates the transplant cannot be performed.

 Negative
Crossmatch: No reaction
between the donor’s and recipient’s
samples occurs.

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Indicates that the recipient’s body will most
likely not reject the implanted kidney.
Indicates the transplant can be performed.