Portada Simposios - Supplements - Haematologica

66 Haematologica (ed. esp.), volumen 85, supl. 2, octubre 2000
known it follows that it is possible to construct oligonucleotide
arrays suitable for blood typing. In
such a procedure a large oligonucleotide array
would be probed with test DNA, hybridisation detected
by fluorescence and data automatically analysed
by computer. In one assay the complete blood
group phenotype of a donor or patient could be determined
by automated objective analysis.
Such comprehensive red cell typing procedures as
those described above would inevitably lead to a reduction
in the incidence of antibodies stimulated by
transfusion but antibody screening procedures would
still be required for complete security, not least, because
most antibodies are stimulated by pregnancy.
Recombinant DNA technology provides new possibilities
for antibody screening methods. Expression of
cDNAs encoding blood group-active molecule in cell
lines or as soluble molecules using in vitro systems has
already been demonstrated for many of the blood
groups including Rh and K. Extraction of antigen
from cultured cells or preparation as soluble molecules
would allow the development of novel antibody
screening systems without the need to use red cells.
Binding of patients’ antibody could be detected by
a fluorescent second antibody and the results read
automatically. In such a system the specificity of antibodies
present would be determined at the same time
they were detected. It would also be possible to design
the system to detect only antibodies of specificity’s
considered to be clinically significant.
Although knowledge of the structure of antigens
has increased considerably since the discovery of
ABO our understanding of the biological significance
of the antigens, outside the unnatural process of
transfusion, has increased rather more slowly. Polymorphism
is greater in human genes encoding proteins
at cell surfaces than in genes encoding intracellular
proteins. This difference appears to be a consequence
of man’s struggle to combat infectious disease.
The differing frequency of some blood group
antigens in different parts of the world may be a reflection
of this struggle for survival.
Most infectious diseases come into contact with
man through the respiratory, gastro-intestinal or urino-genital
route and so the search for linkage between
blood groups and infectious disease is, for the
most part, focused on blood group antigens which
are expressed at mucosal surfaces rather than on the
red blood cell. In some cases polymorphic blood
group antigens are found only on red cells and here
one must look for a relationship with a disease that
affects the red cell directly. Malaria has exerted an
enormous selective pressure on the red cell over millions
of years and there is now substantial evidence
from studies of haemoglobinopathies and South
East Asian Ovalocytosis that individuals who are heterozygous
for the mutations giving rise to these disorders
are protected from the severest manifestations
of malaria. Evidence implicating blood group
polymorphism’s with protection from malaria is less
impressive apart from the protection given by the
Fy(a-b-) phenotype against Plasmodium vivax. It is clear
that mutations in several genes may determine an
individual’s susceptibility to a given disease and we
can confidently expect our understanding of the relationship
between polymorphism and susceptibility
to disease to grow rapidly over the next decade as information
from the human genome project is applied
to this problem. From this new knowledge novel
therapeutic interventions are likely to emerge.