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2336 Part XIII: Transfusion Medicine Chapter 136: Erythrocyte Antigens and Antibodies 2337

RBCs from Rh-positive people have both RhD and RhCE, whereas OTHER BLOOD GROUP SYSTEMS
Rh-negative RBCs have only RhCE. In the Rh system, eight common In terms of transfusion and HDFN, the other blood group systems and
antigen combinations or haplotypes are possible: Dce (R , Rh ), DCe their antigens become clinically relevant only when antibody devel-
0
0
(R , Rh ), DcE (R , Rh ), DCE (R , Rh ), ce (r, rh), Ce (r′, rh′), cE (r′′, ops. Transfusion service laboratories identify (antibody identification)
1
2
2
1
z
Z
y
rh′′), and CE (r , rh ). The letter “d” is commonly used to designate the the specificity and characterize the reactivity of antibodies detected in
y
lack of D, but there is no d antigen or anti-d. routine testing (antibody screening). Once this information is known,
Several nomenclatures can be used to describe Rh genes and antigens. the blood bank assesses the clinical significance of the antibody and
The Fisher-Race nomenclature, which uses CDE terminology, is more selects the most appropriate blood for transfusion. Tables 136–1 and
commonly used for antigens; the Wiener nomenclature, which uses Rh/ 136–2 summarize the number of antigens in each blood group system
rh (or R/r) designations, is favored for haplotypes and gene complexes; and and other relevant information. A detailed description of all the blood
the Rosenfield and Rubinstein nomenclature, which uses numerical desig- group antigens is beyond the scope of this chapter. Because the molec-
nations, was introduced to allow interpretation without bias. 24 ular bases of most blood group antigens and phenotypes are known,
6
The Rh blood group system has over 50 antigens (the ABO system DNA analysis can be used to predict the type of transfused patients and
has 4). By far the most important and immunogenic antigen is D (Rh to identify the fetus at risk for HDFN. 27
0
in Wiener terminology, referring to Wiener’s discovery that a rhesus
monkey injected with human RBCs would produce antibody that agglu-
tinated the RBCs of 85 percent of white New Yorkers). For most clini- GENERAL IMMUNOLOGY OF BLOOD
cal purposes, testing individuals for the D antigen and classifying them GROUP ANTIGENS
as D+ (or Rh-positive), or D– (or Rh-negative) is sufficient. Approxi-
mately 85 percent of the white population is Rh-positive, and 15 percent is An antigen is a substance that can evoke an immune response when
Rh-negative. Most Rh-negative recipients produce anti-D if they receive introduced into an immunocompetent host and react with the antibody
Rh-positive blood. Anti-D can cause hemolysis in adults following an produced from that immune response. An antigen can have several
Rh-mismatched transfusion and in the newborn (HDFN) if antibod- epitopes, which together are called an antigenic determinant, each of
ies were made by the mother from a prior transfusion or pregnancy. which is capable of eliciting an antibody response.
Thus, donors and recipients are routinely typed and matched for D. The ability of an antigen to stimulate an immune response is called
The risk of anti-D sensitization by transfusion is essentially eliminated immunogenicity, and its ability to react with an antibody is called antige-
by matching. The risk of anti-D sensitization in pregnancy is minimized nicity. These primary characteristics are affected by antigen size, shape,
by passive immunization of mothers at risk against D. rigidity, and the number and location of the determinants on the red
The antigens C, c, E, and e are less immunogenic and become cell membrane.
important in patient care only after the corresponding antibody devel-
ops or when the basic Rh haplotype must be determined. The remain- IMMUNOGENICITY
ing 45+ antigens are other Rh protein epitopes whose corresponding Immunogenicity depends on many antigen characteristics, not just
antibodies are seldom encountered. Some are encoded by variant Rh the number of antigen sites. Relative immunogenicity is estimated by
alleles and appear as antithetical antigens to C, c, E, or e, or as related comparing the actual observed incidence of an antibody to the calcu-
“extra” antigens. Others are referred to as compound antigens or lated likelihood of a possible immunizing event. After A and B, the D
cis gene products. For example, the protein produced by RHCE*ce antigen is most immunogenic (early work suggested that approximately
encodes c and e antigens, and the compound f (or ce) antigen. Other 80 percent of Rh-negative individuals produce anti-D after receiving a
compound antigens include Ce (rh ), cE and CE. Still other Rh anti- single Rh-positive RBC component but more recent studies indicate it is
i
4
gens are related to the complex “mosaic” nature of D and e, and less more like 20 to 30 percent ), followed by K, which stimulates anti-K in
16
commonly C, c and E antigens. If immunized, individuals who lack a approximately 10 percent of cases. The antigens c and E are one-third
a
a
part of an antigen and who make antibody to the portion they lack, as immunogenic; Fy is one-twenty-fifth as potent; and Jk is one-fiftieth
28
can present with a challenging serologic picture. For example, the to one-one hundredth times as potent as K. It should be noted that
D+ person who lacks part of the D antigen and makes an antibody immunogenicity does not always correlate with the hemolytic potential
a
to the missing portion appears to make alloanti-D because normal of an antibody specificity; for example, K is more immunogenic than Jk
a
D+ RBCs carry all D epitopes. 25 but anti-Jk is more likely to cause hemolysis.
Some, but not all, individuals who lack part of the D antigen (par-
tial D) have weak expression of D on their red cells that is detected ANTIGEN EXPRESSION
only by the antiglobulin test. Having a RHCE*C gene in trans position
to a RHD gene (e.g., Dce/Ce or DCe/Ce genotypes) also can weaken NUMBER OF ANTIGEN SITES
expression of D in some individuals. A third type of weak D expression The number of antigen sites per RBC has been estimated by measuring
results from inheriting a RHD gene that encodes all epitopes of D, but the uptake of I-labeled antibody or of ferritin-conjugated anti-IgG.
125
in less-than-normal quantity. Numbers vary widely among blood group systems from a few hundred
DNA analyses have revealed the molecular basis underlying anti- to over a million (see Table 136–2). Also, estimates for any given anti-
gens and phenotypes. A list of the alleles that have been described to gen can vary greatly.
date is available at: http://www.ncbi.nlm.nih.gov/gv/mhc/xslcgi.cgi?-
cmd=bgmut/home and www.isbt-web.org. Rh blood group orthologs ANTIGEN DEVELOPMENT ON FETAL
are present in nonhuman primates and other species on the evolution-
ary tree. The RhD and RhCE proteins complex with the Rh-associated ERYTHROCYTES
26
glycoprotein (RhAG) in the membrane. RhAG acts as a transporter of Most RBC antigens can be detected early in fetal development (A, B,
gases, most likely for ammonium, nitrous oxide, CO and/or O but and H antigens can be detected at 5 to 6 weeks’ gestation), but not all
2
2
a
a
confirmation is needed as to which it is. are fully developed at birth. A, B, H, I, P1, Lu , Lu , Yt , Xg , Vel, Bg,
a
b

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