Page 1907 - Hematology_ Basic Principles and Practice ( PDFDrive )

C H A P T E R 110

HUMAN BLOOD GROUP ANTIGENS AND ANTIBODIES

Connie M. Westhoff, Jill R. Storry, and Beth H. Shaz

Pretransfusion testing includes ABO and Rhesus (Rh) type and anti- been given letter designations (A, B, D, M, N, etc.). A committee
body screening to determine whether a patient has an unexpected red for terminology of RBC surface antigens and alleles, organized by the
blood cell (RBC) antibody. If the antibody screen is positive, an International Society of Blood Transfusion (ISBT), works to stan-
identification panel is performed to identify the specificity of the dardize terminology of new blood group antigens and the coding
antibody. Unexpected antibodies can be clinically significant causing alleles.
hemolysis (i.e., acute or delayed hemolytic reaction) after transfusion
of RBCs carrying the reciprocal antigen, or can be insignificant. The
clinical significance of an antibody is assessed by correlating the sero- DNA-Based Typing for Blood Group Antigens
logic information with clinical experiences reported in the literature
and with the patient’s medical history. Notably, the majority of clini- The majority of genes encoding blood group antigens have been identi-
cally significant antibodies (outside the ABO system) are in response fied and cloned, and the molecular basis of most blood group antigens
1,2
to RBC antigen exposure either through transfusion or pregnancy. has been determined. Details concerning the alleles associated with
Other antibody characteristics that are used to predict clinical signifi- blood group antigens are found on the ISBT nomenclature and the
cance include immunoglobulin (Ig) class and in vitro characteristics Blood Group Antigen Gene Mutation Database (BGMUT) websites
such as strength of reactivity and titer; however, no foolproof method (www.ncbi.nlm.nih.gov/gv/mhc/xslcgi.cgi?cmd=bgmut/home;
exists to predict the clinical significance. For antibodies with well- www.isbtweb.org/working-parties/red-cell-immunogenetics-and-
known clinical significance, antigen-negative blood is selected for blood-group-terminology/). Knowledge of the genes has advanced
transfusion. Predicting clinical significance is more difficult when a understanding of the structure and function of the components
patient has an antibody to a novel or rare high-prevalence antigen and carrying antigens and resulted in an appreciation of diseases associated
requires a transfusion but antigen-negative blood is not available. with loss of expression of some blood groups, for example, null phe-
notypes (Table 110.1). Of importance, knowledge of the gene has
made it possible to perform DNA analyses to predict the serologic
ERYTHROCYTE BLOOD GROUP ANTIGENS phenotype, to determine gene dosage (zygosity), to perform noninva-
sive fetal typing, and to type for numerous blood group antigens in a
Erythrocyte blood group antigens are polymorphic, inherited, carbohy- single assay.
drate, or protein structures located on the surface of the RBC membrane. Although the simple hemagglutination test remains the principal
There are more than 300 blood group antigens, most of which are assay for RBC antigen typing for ABO and Rh, antibody screen, and
included in 36 different blood group systems (Table 110.1). The protein compatibility testing; genotyping for minor blood group antigens has
antigens are primarily located on integral transmembrane proteins, but become commonplace in several clinical situations (Table 110.2).
a few are on glycosylphosphatidylinositol (GPI)–linked proteins (Fig. These include determination of the extended blood group phenotype
110.1). Some antigens are carbohydrates attached to proteins or lipids, in patients who are multiply transfused, which avoids false typing
some require a combination of a specific portion of protein and carbo- because of contaminating donor RBCs and aids determination of
hydrate, and a few antigens are carried on proteins that are adsorbed antibody specificity. This approach is also preferred in patients with
from the plasma. Many of the proteins carrying blood group antigens strongly direct antiglobulin test (DAT)-positive RBCs, as well as for
reside in the erythrocyte membrane as complexes with other proteins. typing for antigens when no serologic reagents are available and for
Recognition of a new blood group antigen begins with discovery fetal typing from amniocytes or from free DNA present in the
2a
of an antibody. When an individual whose RBCs lack an antigen is maternal plasma. In these instances and others (Table 110.2),
exposed to RBCs that possess the antigen, he or she may mount an hemagglutination is not helpful and genomic analysis is a useful
immune response and produce antibodies that react with the antigen. adjunct to routine testing. More recently, genotyping is useful in
Depending on the characteristics of the antibody and the number patients treated with daratumumab (anti-CD38) because treatment
and topology of antigens in the RBC membrane, the interaction in results in panreactivity on antibody screening (all cells being reactive).
vivo between antibody and antigen may result in removal of antibody- High-throughput genotyping systems have enabled blood centers to
coated RBCs by the reticuloendothelial system or in hemolysis if screen donors for a large number of antigens in a single assay.
complement is activated.
In blood group testing, most assays are designed to detect
antibody-antigen binding with clumping of the RBCs (“agglutina- Blood Group Antibodies
tion”) as the detectable endpoint. The ability to detect and identify
blood group antigens and antibodies has contributed significantly to The common causes of immunization against blood group antigens
current safe supportive blood transfusion practice, to the appropriate are transfusion, pregnancy, transplantation, or occasionally, practices
management of pregnancies at risk for hemolytic disease of the fetus such as sharing needles. “Naturally occurring” antibodies are not a
and newborn (HDFN), and to management of hematopoietic pro- result of RBC exposure; rather, a response to microbes encountered
genitor cell and solid organ transplantation. by way of the digestive tract and other mucosal surfaces regularly
a
k
(e.g., anti-A, anti-B,) or sometimes (e.g., anti-M, -P, -P , -P1, -Le ,
b
-Le , -I, -IH) which result in production of antibodies with these
Terminology specificities. These are the most common antibodies present in chil-
dren and nontransfused male patients, and are primarily IgM. These
Some blood group systems bear the family surname in which the multivalent IgM antibodies directed to carbohydrate antigens
antibody was first discovered (Kell, Kidd, Duffy, etc.), with abbrevia- optimally bind and directly agglutinate to RBCs at temperatures
b
a
b
a
tions to indicate antigens (K/k, Jk /Jk , Fy /Fy , etc.). Others have below 37°C. Most are not clinically significant (outside of ABO).
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