Page 317 - Essential Haematology

Chapter 23 Stem cell transplantation / 303

of the treatment (Fig. 23.1 ). A limitation of the Chromosome 6
procedure is that tumour cells contaminating
the stem cell harvest may be reintroduced into the HLA-A
patient. Nevertheless, autografting has a major role
HLA-C
in the treatment of haematological diseases such as

lymphoma and myeloma. The major problem asso- HLA-B
ciated with autografting is recurrence of the original HLA region
disease. GVHD is not an issue. Procedure - related
mortality is generally well below 5%.
HLA-DR
HLA-DQ
Centromere HLA-DP
Allogeneic s tem c ell
t ransplantation
(a)
In this procedure, stem cells harvested from another
person are infused into the patient. Th e procedure Peptide Peptide

has a significant morbidity and mortality and one
of the major reasons is the immunological incom- β 1 α 1 α 2 α 1
patibility between donor and patient despite HLA Extracellular

matching. This may manifest as immunodefi ciency, space
β
2
GVHD or graft failure. Paradoxically, there is β 2 α 2 α 3 -m
also a graft - versus - leukaemia (GVL) eff ect which
probably underlies much of the success of the
procedure. Plasma
membrane
The h uman l eucocyte a ntigen s ystem
Cytosol COOH COOH
COOH
Allografting would be impossible without the ability Class II Class I
(b)

to perform HLA typing. The short arm of chromo-
some 6 contains a cluster of genes known as the
Figure 23.5 (a) The human leucocyte antigen (HLA)

major histocompatibility complex (MHC) or the
complex. (b) HLA class I and II molecules showing
HLA region (Fig. 23.5 a). Genes in this region protein domains and bound peptide.
encode the HLA antigens and many other mole-
cules including complement components, tumour
necrosis factor (TNF) and proteins associated with
antigen processing. HLA proteins are divided into

two types: class I and II (Table 23.3 ). Their role is
‘
to bind intracellular peptides and present ’ these to
T lymphocytes for antigen recognition (see Chapter chains, both encoded by genes in the HLA region.
9 ). Class I molecules (HLA - A, - B and - C) present Th e inheritance of the four loci (HLA - A, - B, - C and
+
antigen to CD8 T cells and class II molecules - DR) is closely linked, one set of loci is inherited
+
(HLA - DR, - DQ and - DP) present to CD4 T cells from each parent so that there is approximately a
(Fig. 23.5 b). one in four chance of two siblings having identical
Class I antigens are present on most nucleated HLA antigens (Fig. 23.6 a). Crossing - over of genes
cells and on the cell surface they are associated with during meiosis accounts for occasional unexpected

β 2 - microglobulin. Class II antigens have a more disparities. Th e inheritance is independent of sex or
restricted tissue distribution and comprise α and β blood group.