Biology Reference
In-Depth Information
ch
3
The impact of minor
histocompatibility antigens
in allogeneic stem cell
transplantation
Tuna Mutis
Department of Clinical Chemistry and Hematology, University Medical Center Utrecht, Utrecht, The Netherlands
Els Goulmy
Department of Immunohematology and Blood Bank, Leiden University Medical Center, Leiden, The Netherlands
39
From immunobiology to the impact of mHags in GVHD
and GVT
Starting from the earliest clinical allogeneic transplantation studies, it was
evident that T cells present in the grafts were, by and large, responsible for
the destructive allo-reactivity against hosts' skin, liver and intestines, clini-
cally known as graft-versus-host disease (GVHD)
[1-3]
. Effective control of
this detrimental allo-immunity has been considered as a major challenge
towards improving the clinical outcome of allogeneic bone marrow trans-
plantations (allo-SCT). The initial hope was to eliminate GVHD by either
depleting the T cells or by matching the recipient and the donor for human
leukocyte antigens (HLA), the major transplantation barriers known at that
time. Effective T-cell depletion abrogated GVHD confirming the involve-
ment of alloreactive T cells
[4]
. HLA-matching significantly reduced the inci-
dence of GVHD, yet up to 40% of the recipients developed GVHD even after
receiving transplants from genetically HLA-identical sibling donors
[5,6]
.
Even today, such observations are regarded as the most illustrative evidence
of the existence and prime importance of non-HLA-encoded allo-antigens
in the HLA-matched allo-SCT setting
[7-9]
. These highly immunogenic
allo-antigens are, rather mistakenly, designated as “minor” histocompat-
ibility antigens which are historically abbreviated as “mHag” in the human-
and as “MiHA” in the murine setting. Accordingly, they will be abbreviated
as mHags in this chapter, which mainly deals with human mHags.
Due to the severe toxicity of allo-SCT, research on mHags initially had a strong
focus on understanding the biology and eliminating the harmful immunity
caused by these enigmatic allo-antigens. On the other hand, the clinical asso-
ciation between GVHD and the beneficial graft-versus-tumor (GVT) effect also
suggested a therapeutic role for allo-reactivity mediated by mHags. Due to
the lack of appropriate models in the human setting, however, the impact of
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