a previous exposure to alloantigens through
pregnancy, blood transfusion, or a failed allograft.
Using the microlymphocytotoxicity assay, serum
from the candidate is tested against a standard panel
of lymphocytes that express a wide range of HLA
antigens. The percentage of wells in which lympho-
cyte killing occurs is referred to as the percent panel
reactive antibodies. This measure correlates with
negative lymphocyte crossmatches and thus is
inversely related to the probability of finding a
matching donor.
Following transplantation, the function of the
transplanted tissue is closely monitored in order to
detect surgical complications and to assess the initial
functional status of the tissue. For instance, with the
transplantation of a cadaver kidney, postoperative
oliguria may be due to vascular compromise or a
urine leak or obstruction. If there has been a
prolonged period of ischemia when obtaining the
kidney, the oliguria may be due to preprocurement
acute tubular necrosis.
Organ function is also monitored to detect the
development of rejection. Rejection always leads to
decreased organ function but the laboratory evidence
of a decrement in function may appear relatively late
in the development of the rejection process. This
has lead to the search for early markers of rejection.
Histologic findings of rejection appear early and are
highly reliable. Periodic biopsy of the allograft
therefore offers a way to detect rejection and to
institute anti-rejection therapy before significant
tissue injury has occurred. Because of the invasive-
ness of this monitoring approach, it is only routine
in heart transplantation where the consequences of a
late recognition of rejection are catastrophic.
Numerous laboratory studies of immune function
have been proposed as early markers of allograft
rejection (Waltzer
et al.
1994, Suthanthiran
et al.
1997). Unfortunately, to date, none of these
markers has been demonstrated to be reliable enough
for clinical application. Markers of organ injury are
useful early markers of rejection in transplantation of
the liver and the pancreas. Plasma aminotransferase
concentrations are measured in liver allograft recipi-
ents and urinary amylase concentrations are
monitored in pancreas allograft recipients in whom
the allograft is drained through the bladder. Inter-
estingly, the plasma amylase concentrations is not a
reliable rejection marker in pancreas transplantation.
One would expect that renal injury markers,
especially urinary markers of tubular injury, would
be useful in kidney transplantation but their clinical
utility has not been demonstrated.
Another component of post-transplantation lab-
oratory evaluation relevant to immune injury is the
monitoring of immunosuppressive therapy. The
plasma concentrations of these agents are measured
on a regular basis to assure that the drug concentra-
tions being achieved are high enough to maintain
satisfactory levels of immunosuppression but not so
high that they place the patient at undue risk for
drug-induced toxicity.
Transfusion.
Red cells, which are by far the
most frequently transplanted tissue, do not express
HLA antigens. Other cell surface antigens on red
cells can, however, elicit a typical humoral immune
response in the recipient. These antigens constitute
the various blood group systems. Blood group
matching for transfusion consists of ABO and Rh
typing (Table 9.4). In the case of the ABO blood
group system (Green 1989), naturally occurring
antibodies are invariably present: individuals who
are type A (AO heterozygous) have anti-B
antibodies, type B (BO heterozygous) individuals
have anti-A antibodies, and type O (OO
homozygous) individuals have anti-A, anti-B, and
anti-A,B antibodies. Anti-A,B antibodies are
directed against an epitope shared by the A and B
antigens. These antibodies, which develop in the
first year of life, are predominantly of the IgM class
and cause complement-mediated (intravascular)
hemolysis. The D antigen of the Rh blood group
system (Cartron
et al.
1998) is a potent immunogen
resulting in the production of IgG class antibodies in
Rh negative (D
-
D
-
homozygous) individuals follow-
ing sensitization by transfusion of red cells express-
ing D antigen and in Rh negative mothers following
fetal-maternal hemorrhage from a fetus that is Rh
positive (DD
-
heterozygous or DD homozygous).
These antibodies do not fix complement but they do
induce macrophage uptake of antibody-bearing red
cells by binding to macrophage Fc receptors. This
form of red cell loss is referred to as extravascular
hemolysis.
ABO typing is accomplished by forward and
reverse grouping using the hemagglutination assay.
In forward grouping, one aliquot of a dilute suspen-
sion of test red cells is mixed with reagent anti-A
antibody and another aliquot with reagent anti-B
antibody. The mixtures are briefly centrifuged at
room temperature and then examined for agglutina-
tion. Anti-A antibody agglutinates type A and type
Tissue Injury
9-10
