Page 1915 - Hematology_ Basic Principles and Practice ( PDFDrive )

Chapter 110 Human Blood Group Antigens and Antibodies 1695

of group O red cells and AB plasma products is an option. In blood produced after birth, reaching a peak at 5–10 years of age, and
donors, if very weak expression of A or B antigens on the RBCs is declining with increasing age. The antibodies are mostly IgM and can
not detected, the major risk is that they may be transfused to a patient activate complement, which in conjunction with the high density of
whose antibodies may cause accelerated destruction of the transfused ABO antigen sites on RBCs, are responsible for the severe, life-
cells. threatening transfusion reactions that may result following ABO-
Rare Bombay (O h ) phenotype RBCs, first reported in Bombay incompatible transfusions. In contrast, HDFN caused by ABO
(Mumbai), India, lack H antigen and, consequently, A and B anti- antibodies is usually mild because (1) placental transfer is limited to
gens. Other variants with weak H expression on RBCs, with or the fraction of IgG anti-A and anti-B found in maternal serum, (2)
without H in secretions, also occur (para-Bombay) and have been ABH antigens are not fully developed on fetal RBCs because of a lack
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reviewed. Of clinical relevance, potent anti-H with the same hemo- of fully branched carbohydrate chains, and (3) tissue ABH antigens
lytic potential as anti-A and anti-B can be produced by Bombay provide additional targets for the antibodies.
individuals. Anti-H is often found in para-Bombay individuals but Platelets have intrinsic A, B, and H antigens; thus ABO incompat-
is generally not a potent antibody. HDFN caused by anti-H has not ibility can decrease the posttransfusion platelet increment, but this is
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been reported. often not of clinical significance. However, platelets from donors
Acquired B antigen is a rare phenomenon that results from the with an A 2 phenotype lack both A and H antigens. Approximately
action of bacterial deacetylase, an enzyme that can remove an acetyl 20% of group A platelets would be from A 2 donors and would be
group from the A-terminal sugar, N-acetylgalactosamine. Galactos- appropriate for “universal” use. Platelets from A 2 donors may also be
amine is similar to galactose, the B-specific terminal residue, and a superior product for patients undergoing A/O major mismatch
anti-B reagents can cross-react with the deacetylated structure. allogeneic progenitor cell transplantation. 20
Acquired B can occur in individuals suffering from gram-negative Potent anti-H (along with anti-A and anti-B) found in O h
infections of gastrointestinal origin or carcinoma and can be clinically (Bombay) individuals will destroy transfused RBCs of any ABO
significant if a patient’s blood group is misinterpreted and group AB group, so these individuals must be transfused only with H− RBCs.
blood is transfused. Other polyagglutinable states (e.g., T, Tn, Tk) In contrast, anti-H identified in individuals with low expression of
are detected by naturally occurring antibodies found in the serum of H antigen, notably A 1 B and A 1 , is usually IgM, reacts only at lower
most people; these can be identified by a panel of lectins. temperatures, and is thus clinically insignificant.
A or B antigen expression can weaken in patients with acute
leukemia or stress hematopoiesis or, occasionally, during pregnancy.
Chromosomal deletions or lesions that involve the ABO locus can Other Carbohydrate Blood Group Systems
result in the loss of transferase expression in the leukemic cell popula-
tion. A decrease in A or B antigen expression, when found without As for all glycoconjugate structures, sequential enzymatic action is
a hematologic disorder, can be prognostic of a preleukemic state. required to build other carbohydrate antigenic epitopes, and the
genetic background of all these involves different glycosyltransferase
Genes and Enzymes The ABO gene was cloned in 1990 following loci.
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purification of A transferase; since then, over 200 different alleles have The null p phenotype, P 2 and P 1 , are of clinical interest because
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been described. There are only four amino acid differences between of potent naturally occurring antibodies that are present in plasma of
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A and B transferases in the catalytic domain, two of which (Leu- individuals whose RBCs lack the glycolipid-based antigens P1/P/P ,
266Met and Gly268Ala) are primarily responsible for the substrate P1/P/PX2, or P/PX2, respectively. In analogy with the ABO blood
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specificity. The group O phenotype results from mutations in ABO group system, antibodies of IgM and IgG class (anti-PP1P , anti-
that cause a loss of glycosyltransferase activity. The most common P1PPX2, or anti-PPX2) are made against the missing antigens.
group O allele (ABO*O1) results from a single nucleotide deletion Although the incidence of the null phenotypes is only 5–10 per
near the 5′ end of the gene that causes a frameshift and early termina- million, they have attracted considerable interest because of their
tion with no active enzyme production. The rare B(A) and cis-AB relationship to disease and as receptors for pathogens. Women with
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phenotypes have both A and B enzyme activity from a single allele p and P phenotypes suffer a high incidence of spontaneous abortion,
caused by variant glycosyltransferases that have a combination of a phenomenon most likely caused by destruction of the placenta by
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A-specific and B-specific residues. anti-P. In addition, anti-P and anti-P cause hemolytic transfusion
The fucosyltransferases required for H synthesis are encoded by reactions if antigen-positive RBCs are transfused. Transient autoanti-P,
two closely linked genes on chromosome 19, FUT1 (or H) and FUT2 produced following a viral infection, causes paroxysmal cold hemo-
(or Se for secretor), which have different substrate specificity and globinuria and lysis of autologous P-positive RBC. P antigen (also
expression in tissues. Homozygosity for defective FUT2 alleles is known as globoside) is the cellular receptor for the parvo-B19 virus
responsible for the common nonsecretor phenotype in which A, B, that causes erythema infectiosum (fifth disease) in children, some-
and/or H antigen are not present in secretions. Individuals homozy- times complicated by severe aplastic anemia because of lysis of early
gous for null alleles at both the FUT1 and FUT2 loci have the erythroid precursors. P-fimbriated Escherichia coli expresses both
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Bombay phenotype (see earlier section). P-binding and P -binding molecules at the tips of their pili, a finding
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with implications for uropathogenicity. Individuals lacking P, or P
ABO and Transplantation As tissue antigens, ABO antigens are and P, appear to be naturally resistant to these bacterial and viral
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important in solid organ transplantation. Recipient antibodies will infections. In contrast to anti-P and anti-P , it should be noted that
react with antigens on the transplanted organ and complement anti-P1 is a cold-reactive agglutinin that seldom has clinical impor-
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activation at the surface of endothelial cells can result in rapid tance. The clinical importance of anti-PX2 made by P individuals is
destruction and hyperacute rejection. However, successful transplan- unclear.
tation across ABO barriers is possible, particularly with blood group Lewis antigens are fucosylated glycolipids that are synthesized by
A 2 to O and with current immunosuppressive and pretreatment regi- nonerythroid cells, circulate in plasma, and are passively adsorbed
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ments including removal of ABO antibodies. Allogeneic hemato- onto RBC. Antibodies to Lewis can be made by individuals with the
poietic stem cell transplantations are routinely performed regardless Le(a−b−) phenotype. These antibodies are of IgM class and seldom
of ABO compatibility, but occasionally initial hemolysis or pure red cause any clinical problems. Lewis antibodies are commonly found
cell anemia because of persisting anti-A or anti-B titers in the recipi- in pregnant women.
ent can result. The i and I antigens are nonterminal epitopes on linear and
branched carbohydrate structures, respectively, carrying ABH anti-
Antibodies Anti-A and anti-B are found in the sera of individuals gens at their terminal ends. During the first years of life, linear chains
who lack the corresponding antigens. They are produced in response are modified into branched chains, resulting in the appearance of I
to environmental stimulants, such as bacteria. These antibodies are antigens. The i phenotype is very rare among adults, but it is the