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2342 Part XIII: Transfusion Medicine Chapter 136: Erythrocyte Antigens and Antibodies 2343

and p55, which are involved in cell deformability and membrane stabil- quickly during storage, even though they demonstrate normal osmotic
53
ity. Gerbich-negative RBCs of the Leach type (Ge:–2, –3, –4) lack both fragility. Inactivating nucleotide changes in KLF1, which encodes an
GPC and GPD, have reduced protein 4.1, and elliptocytosis but exhibit altered transcription factor, cause the InLu phenotype. 30
normal survival in vivo. 6,10 The Jk(a–b–) phenotype is caused by the silent alleles JkJk or the
dominant inhibitor In(Jk). RBCs having the Jk(a–b–) phenotype resist
54
Bombay (O ) Phenotype lysis in 2M urea, a reagent commonly used in automated platelet
h
Rare people lack A, B, and H antigens and have naturally occurring counting systems; resulting in erroneously high platelet counts. No
anti-A, anti-B, and anti-H in their plasma. Such people are said to have significant clinical abnormalities have been identified to date, although
55
the Bombay (O ) phenotype. In rare people with the Le(a–b–) Bombay Jk(a–b–) individuals have reduced ability to concentrate urine.
h
phenotype, the gene that encodes the Fuc transporter is silenced. As The following diagnoses are made easily by simply typing the RBCs
a consequence, all cells lack Fuc. Without Fuc, neutrophils lack sialyl with appropriate antisera: Rh syndrome, McLeod syndrome, and LAD II.
Le and thus cannot roll and ingest bacteria. These patients have a high
X
white blood cell count and severe recurrent infections. The condition is
called leukocyte adhesion deficiency II (LADII) or congenital disorder of ERYTHROCYTE ANTIBODIES
glycosylation II (CDG II). 45,46
IMMUNOLOGY OF RED CELL ANTIBODIES
I-Negative Phenotype (i Adult) Blood group antibodies are classified as alloantibodies if they only react
The gene encoding the I-branching β-1,6-N-acetylglucosaminyltrans- with antigens present on the RBCs of other people and as autoantibodies
ferase (GCNT2) has three alternative forms of exon 1, with common if they react with self-antigens present on the patient’s own RBC. Alloan-
exons 2 and 3. Mutations in exon 2 or 3 silence GCNT2 and give rise to tibodies also can be classified according to their mode of sensitization
the form of I-negative phenotype associated with congenital cataracts as naturally occurring (no apparent sensitization) or immune (following
in Asians. 47,48 Mutations in exon 1C (IGnTC or IGnT3) silence the gene sensitization). Table 136–5 summarizes the common anti-erythrocyte
in RBCs but not in other tissues, and lead to the I-negative phenotype antibodies. 4,6,15,16
(i adult) without cataracts. 49
IMMUNOGLOBULIN CLASSES ASSOCIATED
CO Phenotype WITH BLOOD GROUP ACTIVITY
null
Antigens of the Colton blood group system are carried on the water
transporter (aquaporin [AQP1]). Although an absence of this protein Immunoglobulin G
from the RBC membrane was thought to be incompatible with life, in IgG is the predominant antibody made in an immune response and
reality these rare individuals have been shown only to be unable to max- constitutes approximately 80 percent of total serum Ig (Chap. 75). These
imally concentrate urine. 50 antibodies, when specific for RBC antigens, can attach to or induce
hemolysis of transfused antigen-positive RBCs. Receptors on macro-
RAPH Phenotype phages in the liver and spleen allow the macrophages to remove IgG-
null
The MER2 antigen in the RAPH blood group system is carried on coated RBCs from the circulation. IgG blood group antibodies also
CD151. Rare individuals who lack CD151 have chronic renal failure, are capable of fixing complement, although some subclasses do so less
skin ulcers, and deafness. 51 efficiently than others: IgG > IgG > IgG > IgG . How well an IgG ery-
2
4
1
3
throcyte antibody binds complement, depends on the surface density
Other Null Phenotypes and location of the recognized antigen. This situation occurs because
Patients with null phenotypes can develop RBC antibodies that make C1q, the initiator of the classic complement cascade, requires binding
it difficult to find compatible blood to avoid the otherwise serious of at least two IgG molecules to the RBC within a span of 20 to 30 nm
hemolytic transfusion reactions. For example, people with the Bombay to initiate the complement cascade. For example, IgG anti-D rarely
16
phenotype (O or H ) demonstrate no red cell abnormality but make binds complement, presumably because most D sites are spaced too
null
h
16
potent hemolytic anti-H as well as anti-A and anti-B. These antibodies far apart. Most IgG blood group antibodies do not agglutinate saline-
are incompatible with all RBCs except those from other persons with suspended RBCs, presumably because the IgG molecule is too small to
k
the Bombay phenotype. Likewise, p individuals (PP1P -negative) or P span the distance between RBCs, although some exceptions are known
k
individuals (P-negative) can make hemolytic antibodies to the antigens (i.e., potent IgG examples of anti-A, anti-B, anti-M, and anti-K). Some
they lack. Anti-PP1P and anti-P also are associated with spontaneous IgG anti-D can directly agglutinate RBCs with the D-phenotype. Most
k
abortions in the first trimester. Women with such antibodies (notably IgG antibodies sensitize RBCs at 37°C and are detected with an anti-
16
IgG anti-P), even those with a history of spontaneous abortions, have globulin reagent. 11
delivered viable infants after plasmapheresis. 52
Null phenotypes in the MNSs and Lutheran systems are interesting Immunoglobulin M
because several types of null phenotypes are known. Within the MNSs IgM is a pentamer of five basic units (having μ heavy chains plus a short
blood group system, people may lack GPA (En[a–] or MN-negative), J, or joining, chain) and makes up only approximately 4 percent of total
GPB (SsU-negative), or both (M M phenotype). The rare Lu(a–b–) serum Ig (Chap. 75). IgM is the first class of Ig produced by the fetus
k
k
phenotype is caused by a dominant inhibitor called In(Lu), by homozy- and is the predominant antibody in a primary immune response, but it
gous pairing of the silent allele Lu, or by a recessive sex-linked inhibitor does not cross the placenta. Because of their pentameric structure, even
5,16
XS2. Only the LuLu-type null (recessive Lu[a–b–]) is associated with low-affinity IgM blood group antibodies can agglutinate RBCs and acti-
antibody production because the inhibitor type nulls produce small vate complement. Both hemolyzing and agglutinating abilities of IgM
amounts of Lutheran antigen. In(Lu) type, Lu(a–b–) RBCs have low molecules are destroyed by reducing reagents, such as 2-ME and DTT.
expression of CD44 and AnWj, and have varying degrees of poikilo- IgM antibodies of low affinity may agglutinate RBCs only at temper-
cytosis and acanthocytosis. RBCs of this type tend to hemolyze more atures below 37°C. Such antibodies still may fix complement onto the

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