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CHAPTER 136 using biochemical and molecular genetic methods. Orphan antigens of
low or high prevalence are placed in “holding tanks” until the gene that
ERYTHROCYTE ANTIGENS encodes them is established.
The majority of genes encoding blood group antigens have been
2
AND ANTIBODIES cloned and sequenced, and the molecular bases of most blood group
antigens have been determined. Details on the alleles associated
3–6
with blood group antigens and phenotypes can be obtained from the
National Center for Biotechnology Information (NCBI) “dbRBC”
Marion E. Reid and Christine Lomas-Francis website: http://www.ncbi.nlm.nih.gov/gv/mhc/xslcgi.cgi?cmd=bgmut/
home and from the International Society of Blood transfusion (ISBT)
website: www.isbt-web.org.
RBC antigens are inherited carbohydrate or protein structures
SUMMARY located on the outside surface of the RBC membrane (Fig. 136–1).
Although most of the protein blood group antigens are carried on inte-
Blood group antigens are structures on the outer surface of human red blood gral transmembrane proteins (either single-pass type I or type II, or
cells (RBCs) that can be recognized by the immune system of individuals who multipass; Fig. 136–1), a few are carried on glycosylphosphatidylinosi-
lack that particular structure. Identification of RBC antigens and antibodies has tol (GPI)-linked proteins or adsorbed from plasma. Some carbohydrate
been the basis of pretransfusion compatibility testing and the safe transfu- antigens are attached to proteins or lipids and some require a combi-
sion practices used today and also can provide insights into understanding the nation of a specific portion of protein and carbohydrate. Blood group
etiology of hemolytic disease of the fetus and the newborn. Biochemical and antigens have revealed that certain transmembrane proteins interact
molecular studies have led to definition of the biologic functions of molecules with other transmembrane proteins (e.g., band 3 and glycophorin A
expressing blood group antigens. These molecules play a critical role in suscep- [GPA]; Kell and Kx; Rh and RhAG), with lipids (e.g., Rh), or with pro-
teins in the membrane skeleton (e.g., band 3 and ankyrin, glycopho-
tibility to infection by malarial parasites, some viruses, and bacteria. Alteration rin C [GPC], and protein 4.1 and p55). Many of the proteins carrying
of RBC antigen expression is associated with many molecular backgrounds and blood group antigens reside in the erythrocyte membrane as com-
some play a role in the clinical manifestations of certain diseases. Erythrocytes, plexes. 7–10 Many components carrying blood group antigens have been
far from being inert containers of hemoglobin, are active in a variety of phys- assigned cluster of differentiation (CD) numbers (Table 136–1). In human
iologic processes. blood grouping, agglutination of RBCs usually serves as the detectable
11
end point, but it can also be hemolysis. Our ability to detect and iden-
tify blood group antigens and antibodies has contributed significantly
to current safe blood transfusion practice, reducing death from hemo-
DEFINITIONS AND HISTORY lytic disease of the fetus and newborn (HDFN) from 40 percent to less
than 2 percent, and supporting patients receiving chemotherapy or
A blood group system consists of a group of antigens encoded by alleles organ transplantation.
at a single gene locus or at gene loci so closely linked that crossing over The naming of blood group antigens usually does not follow the
does not occur or is very rare. An antigen collection consists of antigens classic convention wherein dominant traits are given capital letters
that are phenotypically, biochemically, or genetically related, but the and recessive traits are designated with lowercase letters. For example,
1
genes encoding them have not been identified. Placement of a blood in the ABO blood group system, A and B are codominant and the
group antigen into a system or collection begins with the discovery of recessive O phenotype is encoded by a gene designated O, whereas
an antibody, usually in the serum of a multiparous woman or a multiply in the MNS system the genes S and s are codominant. To standardize
transfused recipient, with a unique pattern of reactivity. The antibody terminology used to describe RBC blood groups, the ISBT Working
can be used to study basic biochemical properties of the corresponding Party for Terminology for Red Cell Surface Antigens recommended
antigen, to enable recognition of the pattern of inheritance of the anti- using the traditional name for an antigen for verbal communication
gen in families and in populations, to identify red blood cells (RBCs) and a numerical system in computer databases (see Blood Group Ter-
that lack the antigen, and to search for an antithetical antigen. Identified minology website at www.isbt-web.org). The working party has placed
characteristics, such as prevalence of positive reactions or sensitivity blood group antigens into four categories: (1) genetically discrete
or resistance to specific enzymes, are compared to antigens in known blood group systems; (2) serologically, biochemically, or genetically
systems and collections. A newly recognized antigen is also evaluated related antigens in blood group collections; (3) series of low-incidence
antigens; and (4) series of high-incidence antigens. Each system and
collection has been given a number and letter designation, and each
antigen within the system is numbered sequentially in order of dis-
covery. At the time of going to press (2015), 35 blood group systems
Acronyms and Abbreviations: AET, 2-aminoethylisothiouronium bromide; and 6 antigen collections are defined (see Table 136–1; www.isbt-
CD, cluster of differentiation; DTT, dithiothreitol; GPA, glycophorin A; GPB, web.org). 1,5,6,12–14 Over time, notations devised to describe blood group
glycophorin B; GPC, glycophorin C; GPD, glycophorin D; GPI, glycosylphos- antigens have changed. A single letter (e.g., A, D, K), a symbol with
phatidylinositol; HDFN, hemolytic disease of the fetus and newborn; HEM- a superscript (e.g., Fy , Jk , Lu ), a symbol with a number (e.g., Fy3,
b
a
a
PAS, hereditary erythroblastic multinuclearity with a positive acidified serum Lu4, K12), and three to four letters (e.g., Vel, JMH, ELO, FPPT) are
test; Ig, immunoglobulin; ISBT, International Society of Blood Transfusion; all used, sometimes within the same blood group system. The ISBT
LAD, leukocyte adhesion deficiency; 2-ME, 2-mercaptoethanol; PNH, parox- Working Party name has changed to ISBT Working Party on Red Cell
ysmal nocturnal hemoglobinuria; RBC, red blood cell. Immunogenetics and Blood Group Terminology, which reflects that
DNA testing is now often used to predict a blood group.

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