Page 1918 - Hematology_ Basic Principles and Practice ( PDFDrive )

1698 Part XI Transfusion Medicine

screening of the fetal middle cerebral artery peak systolic velocity is detection in the sensitized patient’s serum before transfusion. JK
used to monitor anemia. Other unusual consequences of Kell anti- antibodies only rarely cause HDFN, and if they do, it is typically not
ab
bodies include risk for fetal thrombocytopenia and neutropenia. severe. Anti-Jk3, sometimes referred to as anti-Jk , is produced by
Jk(a−b−) individuals, and rare donors must be located for
McLeod Syndrome This uncommon syndrome is associated with transfusion.
the loss of expression of Kx protein caused by mutations and deletions
23
in the XK gene. The syndrome, which is X-linked and manifests MNS System
only in males, may be underdiagnosed. The physical characteristics, M and N antigens are carried on alternative forms of glycophorin
which often develop only after the fourth decade of life, include A (GPA), whereas S and s antigens are carried on alternative forms
muscular and neurologic problems. A minority of patients with of glycophorin B (GPB). M/N and S/s are homologous proteins
chronic granulomatous disease also have the McLeod phenotype as a encoded by adjacent genes and consequently show linkage disequi-
result of X-chromosome deletions encompassing both genes. Carrier librium in inheritance of the antigens. The MNS system is highly
females have two populations of RBCs (one of the McLeod pheno- polymorphic and most of the 49 antigens are the result of amino acid
type and one of normal phenotype). substitutions or rearrangements between GYPA and GYPB. Persons
who are S−s− are usually of African origin. They either also lack
Duffy Blood Group System the high-prevalence U antigen arising from a deletion of GYPB
The Duffy (FY), previously known as DARC now designated ACKR1 or express variant weak U antigen as a result of an altered form
for atypical chemokine receptor, glycoprotein is a promiscuous che- of GYPB.
mokine receptor found on RBCs and on endothelial cells in the
kidney and brain that binds a family of chemotactic and proinflam- Antibodies Anti-S, anti-s, and anti-U are usually IgG and can be
matory peptides from the CXC (IL-8, MGSA) and the CC (RANTES, clinically significant antibodies. Anti-M and anti-N can be naturally
MCP-1, MIP-1) classes. The physiologic role of FY is clear, but on occurring, may be reactive at room temperature or below, and are
RBCs the receptor may allow RBCs to act as scavengers for excess often clinically insignificant.
chemokines. FY is also a receptor to which Plasmodium vivax mero-
zoites can bind to invade RBC and cause malaria.
Other Protein Antigens
a
b
Antigens The Fy and Fy antigens differ by a single amino acid
(Gly42Asp) located on the N-terminal extracellular domain of the Antibodies to antigens in the following systems are less common than
FY glycoprotein and is responsible for the common Fy(a+b−), those described earlier in this chapter, and information regarding
Fy(a−b+), and Fy(a+b+) phenotypes. The null Fy(a−b−) phenotype their general clinical significance is summarized in Table 110.3.
is rare in most ethnic groups, but it is common in people of African
and Arabian origins. The null phenotype most often results from a Lutheran System
mutation in the promoter region of FY that disrupts a binding site Lutheran (Lu), along with Secretor, provided the first example of
for the erythroid transcription factor GATA-1 and results in loss of autosomal linkage in humans, the first example of autosomal crossing
24
FY on RBCs. Because the erythroid promoter controls expression over, and the first indication that crossing over in humans is more
only in erythroid cells, FY expression in other tissues is unaffected. common in females than in males. The Lu system consists of four
All individuals of African origin with a mutated GATA box to date antithetical pairs of antigens and 16 independent high-prevalence
b
have been shown to carry FYB and therefore Fy is expressed on antigens. The Lu(a−b−) phenotype is rare, but in the majority of
nonerythroid tissues. This explains why Fy(a−b−) individuals make individuals, it is caused by heterozygosity for silencing mutations in
a
26
b
anti-Fy but not anti-Fy . Fy(a−b−) caused by a mutated GATA box the EKLF/KLF1 gene. KLF1 is a transcription factor that regulates
on an FYA allele has been found in Papua New Guinea, another many erythroid-specific genes, and the expression of antigens in other
malaria-endemic region. blood group systems (e.g., Kn, In) is also affected. In one family,
heterozygosity for a mutation in the GATA1 gene was shown to be
Antibodies FY antigens are much less immunogenic than Rh and responsible for the Lu(a−b−) phenotype.
b
a
K. Anti-Fy is less common than anti-Fy , and both antibodies can
cause delayed hemolytic transfusion reaction (DHTR) and rarely Antibodies Antibodies in this system are rarely encountered because
HDFN. Anti-Fy3 is made by Fy(a−b−) individuals who are excep- the antigens are not highly immunogenic. They are usually IgG and
tions to above, and it is speculated they may lack FY protein on all give characteristic agglutinates surrounded by unagglutinated RBCs.
cells. They can cause mild transfusion reactions, but do not typically cause
HDFN. Anti-Lu3 is found in the serum of immunized people of
Kidd Blood Group System the rare recessive Lu(a−b−) phenotype, and the antibody is usually
The Kidd (JK) blood group protein was implicated in urea transport IgG and may cause DHTR or HDFN. Blood with the Lu(a−b−)
when RBCs lacking the antigens were shown to resist lysis in 2 M phenotype should be used for transfusion of patients with these
urea. The protein is present in RBCs and kidney medulla and is a antibodies.
constitutive urea transporter, but failure to express Kidd does not
result in an overt clinical syndrome; the only observed manifestation Diego System
is a reduced capacity to concentrate urine. 25 The Diego (Di) blood group antigens are on Band 3 anion transport
protein (AE1), one of the most abundant erythrocyte glycoproteins.
a
b
Antigens The Jk and Jk antigens differ by a single amino acid AE1 forms complexes with many other proteins in the cell membrane
(Asp280Asn) and are responsible for the common Jk(a+b−), Jk(a−b+), and is important for RBC stability. The Diego blood group system
and Jk(a+b+) phenotypes. The Jk(a−b−) or Jk null phenotype is contains three antithetical pairs of antigens and 16 low-prevalence
b
uncommon and occurs with greater incidence in Polynesians, Asians, antigens. Di antigen has a prevalence of greater than 99.9%, but Di a
and Finns. Many different molecular changes in both JKA and JKB is rare in most populations. Exceptions include South American
a
alleles have been shown to abolish expression of the Kidd blood group Indians (Di occurs in 54% of this population) and North American
a
b
protein. Weakly expressed variants of Jk and Jk antigens are also not Indians, approximately 12% of whom are Di(a+).
uncommon.
Antibodies Di antibodies are usually IgG and do not bind comple-
Antibodies JK antibodies are responsible for at least one-third of ment. These antibodies have caused DHTR (usually delayed) and
cases of DHTR. The antibodies often drop to undetectable levels or HDFN. Autoantibodies to band 3 are common in patients with
react only with cells that are homozygous for the antigen and escape warm autoimmune hemolytic anemia.