Biomedical Engineering Reference
In-Depth Information
genetic organization of the MHC Class II region is more complex. HLA-DR,
HLA-DQ, and HLA-DP gene clusters code production of correspondingly named
proteins characterized as class II antigens—which contain two dissimilar (alpha and
beta) chains. Numerous genes of the HLA-DQ and HLA-DP clusters are most likely
pseudogenes. Placed between the class I and the class II region, in the central part
of MHC is a cluster of genes, designated as class III, encoding various biologically
active proteins, such as complement components (e.g., C2, C4A, and C4B), tumor
necrosis factor-a (TNF- a ), lymphotoxin- a , lymphotoxin- b, etc. These genes are
involved in various inflammation events and various aspects of stress, inflammatory,
or immune response [
6-
8
] .
The products of HLA system are glycoproteins placed on the surface of cell
membranes and play a key role in antigen presentation. HLA class I molecules are
found on the surface of most nucleated cells, such as lymphocytes, granulocytes,
monocytes, platelets, and cells of solid tissues. On the contrary, mature red blood
cells (RBCs) do not have HLA antigens, but erythroid progenitors contain them.
Class II molecules have more limited cell distribution; they are expressed on B lym-
phocytes and cells of monocyte-macrophage lineage always, and on T lymphocytes
and some other cells after appropriate stimulation [
6
] .
The transplant of hematopoietic stem cells (SCs) is a potentially curative therapy
for a variety of hematological and non-hematological diseases. The main biomedi-
cal interest in the HLA system originated right from transplant biology, as a result
of organ and tissue transplant practice [
9-
13
]. Matching of donor and recipient for
HLA antigens is essential for the success of SC transplant [
14-
16
] . Namely, HLA
and ABO antigens have a central role in the long-term survival of the transplants. In
contrast, recognition of differences in HLA antigens is probably the first step in the
rejection of transplanted organs or tissues. HLA system has also important role in
the pathogenesis of different adverse effects of the blood component therapy, involv-
ing immune-mediated platelet refractoriness, febrile nonhemolytic transfusion reac-
tions (FNHTRs), transfusion-related acute lung injury (TRALI), and graft-versus-host
disease (GvHD). Finally, in response to pregnancy, transfusion, or SC transplant,
immunologically normal persons are more expected to develop antibodies again
HLA antigens than to any other blood group system [
6
] .
As mentioned, HLA testing is an integral part of cell, tissue, and organ transplant
[
12-
14
]. In relation to genetic, that is, HLA relationship between donor and recipi-
ent, transplants can be classified as autologous, allogeneic, and syngeneic.
Autologous transplant is not strictly an authentic transplant, but rather a resuscita-
tion of a patient with his or her own SCs after myeloablative radio-chemotherapy. In
fact, SCs are reinfused to repopulate the lethally or sublethally damaged recipient's
bone marrow. Allogeneic transplant includes application of cells from another per-
son, that is, HLA-matched related or unrelated donor in order to rescue the patient
following an intensive antitumor therapy. In the special case of an identical twin
recipient and donor, such transplants are referred to as syngeneic [
6
] . The donor
selection is made essentially based on an HLA-match, while donor-recipient
RBC-incompatibility is considered secondarily. Differences inside HLA system
between donor and recipient represent the most important barrier to SC transplant.
