The ABO blood group system was the
first system described and remains the most significant used for transfusion
medicine. A mismatch of ABO may be fatal, whereas a mismatch of other blood
groups initially is harmless. This situation occurs because anti-A and anti-B
usually are present in the blood of adults lacking the corresponding antigen.
These antibodies are stimulated by the ubiquitous distribution of the antigen
that forms part of the membrane structure of many bacteria, plants, and
animals. For this reason, all donor blood for transfusion is tested and labeled
with the ABO group. The four main phenotypes are A, B, AB, and O, the latter
indicating a lack of both A and B antigens. The sugars defining A and B
antigens are added to carbohydrate chains carrying the H antigen (fucose),
which is "hidden" by the A or B sugar. Thus group A or B erythrocytes
appear to have less H antigen than group O cells. Nonetheless, H is found on
all human erythrocytes except those in rare individuals of the Oh
(Bombay) phenotype.
Anti-A or anti-B can cause
intravascular hemolysis when ABO-incompatible RBCs are transfused. Because A
and B antigens also are expressed on most tissue cells, ABO compatibility is a
significant consideration in solid organ transplantation. However, ABO
incompatibility only rarely causes clinical HDN because antibodies directed
against A and B antigens are predominantly immunoglobulin (Ig)M, which do not
cross the placenta, and because A and B antigens are not fully developed on
RBCs from a fetus.
Although the ABO blood group system
has only four phenotypes, more than 90 alleles have been identified by DNA
analyses. The ABO gene was cloned in 1990 following purification of A
transferase.17,18 A and B transferase have only four amino acid
differences in the catalytic domain, two of which (Leu266Met and Gly268Ala) are
primarily responsible for substrate specificity.19 The group O
phenotype results from mutations in A or B alleles that cause loss of
glycosyltransferase activity. The most common group O (O1) results
from a single nucleotide deletion near the 5' end of the gene that causes a
frameshift and early termination with no active enzyme production.20
The ABO gene has seven exons, and A or B subgroups (with only few
exceptions) result from a variety of mutations in exon 7 that cause alterations
in the catalytic domain of the glycosyltransferase (reviewed by Chester and
Olsson21). The rare B(A), A(B), and cis-AB phenotypes
expressing both A and B antigens result from variant glycosyltransferases that
have a combination of A- and B-specific residues.22,23 Numerous
common and rare ABO alleles have been reported, and current information
is available on the blood group antigen gene mutation database web site (http://www.aecom.yu.edu).
In addition to single point mutations, recombinations and gene rearrangements
can result in hybrids with unexpected activity of the transferase. This
situation makes typing of ABO by DNA analysis difficult to interpret.24
The function of the ABO system is not known, although several disease
associations are well established.
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