Chapter 08 Blood Group Terminology and the Other Blood Groups

• This section covers blood group terminology and the organization of antigens, including correct terminology usage for antigens, antibodies, phenotypes, and genotypes.

Blood Groups and Terminology

• ABO and Rh blood groups are most significant in transfusion, but over 300 RBC antigens are formally recognized internationally.
• Blood group antigens can be defined by carbohydrates (sugars) attached to glycoprotein or glycolipid structures or by amino acids on a protein.
• Lewis, P, and I carbohydrate blood groups' genes encode glycosyltransferases that synthesize carbohydrate epitopes by sequential addition of sugars.
• MNS, Duffy, Kell, and Kidd blood groups are significant in routine transfusion medicine because antibodies to these antigens are more commonly encountered.
• Discussed are remainder of blood groups and selected antigens with antibodies that will be rarely encountered; but it is important for clinical laboratorians to be aware of them.
• The effects of enzymes and chemical treatments on test RBCs is discussed for each blood group presented.
• A blood group system involves one or more antigens produced by alleles at a single gene locus, or at loci so closely linked that crossing over is very rare.
• Most blood group alleles are codominant and express matching antigen; some genes code for complex structures carrying more than one antigen.
• Silent/amorphic alleles are rare, but when paired chromosomes carry the same silent allele, a null phenotype results which can be helpful when evaluating antibodies.
• Some blood group systems have regulator/modifying genes that alter antigen expression.
• Blood group antigens are detected by alloantibodies, occurring naturally or due to immune response after exposure to non-self RBC antigens from transfusion/pregnancy.
• Blood group antigens have been named using uppercase/lowercase letters, system names, and letters followed by numbers/uppercase letters.
• Genes are written in italics or underlined, allele letter/number is always superscript which may lead to confusion.
• Antigen names are written in regular type.
• Phenotype describes which antigens are present on an individual's RBCs; indicates the results of serologic tests on those RBCs.
• Use subscripts, superscripts, and italics appropriately.
• Presence/absence of letter antigens is designated by plus/minus sign on the same line as the antigen.
• When testing for both antithetical antigens, both results are written within the same parentheses.
• For antigens with a numerical designation, the system is followed by a colon, then the number representing the antigen; no plus sign if present, minus sign if absent.
• Multiple results are separated by a comma (e.g., Sc:-1,2).
• Phenotypes of >1 blood group system are separated by a semicolon (e.g., S+s+; K-; Fy[a+b−]).
• Serologic tests determine RBC phenotype, not genotype; genotype (actual inherited genes) is determined by family/DNA studies.
• Numeric terminology was introduced for Kell/Rh systems, then applied to others to facilitate computer storage/help standardize names.
• The International Society of Blood Transfusion (ISBT) formed the Working Party on Terminology for Red Cell Surface Antigens in 1980.
• The numeric system to enable communication on computer systems where numbers are necessary.
• The first 3 numbers represent system, collection, or series; the next 3 identify the antigen.
• Each system also has an alphabetical symbol.
• The ISBT assigns antigens to a system, collection, or low/high-prevalence series, where a blood group system "consists of one or more antigens controlled at a single gene locus".
• Collections have biochemical, serologic, or genetic relationships but don't meet system criteria, assigned a 200 number; some collections made obsolete as criteria was met for inclusion in a system
• Remaining RBC antigens not associated with system/collection are cataloged in the 700 series of low-prevalence antigens or the 901 series of high-prevalence antigens.

The Lewis System

• Lewis blood group system is unique; Lewis antigens aren't intrinsic to RBCs, but are type 1 glycosphingolipids adsorbed from plasma.
• Named after one of the first individuals to make the antibody, reported by Mourant in 1946.
• Antibodies to Lea reacted and agglutinated RBCs from about 25% of English people, later called anti-Leb, was discovered which reacted with Le(a−) individuals
• The Lewis system's ISBT number is 007 and the system symbol is LE by fucose transferases with independent interaction of genes (Le and Se)

The P System

• The P blood group comprised the P, P1, and Pk antigens and later, Luke (LKE), but molecular biochemistry has made it clear this not a single system
• In ISBT nomenclature, P1 and Pk are assigned to the P1PK blood group system (003, P1PK); Pis assigned to the Globoside blood group system (028, GLOB); GLOB is the symbol for both

The I System

• The existence of cold agglutinins in the serum of normal individuals and in patients with acquired hemolytic anemia has long been recognized.
• Wiener and coworkers gave a name to one such agglutinin and called its antigen I for "individuality" as the antibody reacted with specimens tested.
• Exceptions were from homozygotes for a rare gene producing the "i" antigen; the I- phenotype in adults is now called adult i, though I and i are not antithetical antigens.
• I and i are branched and linear carbohydrate structures formed by glycosyl transferases
• I raised to system status (system number 027, symbol I) and i antigen remains in I/i collection (collection number 207, symbol I).
• Antibody testing can enhance reactivity to I and i with treatment depending on use of DTT, enzymes, and glycine-acid EDTA.

MNS Blood Group

• Landsteiner and Levine, following the discovery of the ABO blood group initiated research to discover antibodies from rabbits
• Both family and molecular studies have demonstrated the tight linkage between the M, N, S and s expression as well as their antigenic presence
• The term “U” denotes the “universal” antibody prevalence has also been included in the system
• Consisting of 46, a plethora of both low and high-prevalence and complex carbohydrate proteins of different classes associated with HDFN and incompatible crossmatch with limited encounter
• The ISBT nomenclature is the MNS blood group (Symbol, MNS & assigned a ID of 002)
• The basics of the system exist on highly characterized levels involving glycoprotein formation where the antigen strength may vary from one individual to the next
• Glycophorin A (GPA): M and N antigens
• Glycophorin B (GPB): S and s antigens

The Kell System

• It can be described as starting with 1946 and growing with a multitude of antigens through 1963 (Jsb described) and beyond in relation to the Kell system.
• The discovery of the null phenotype in 1957 helped associate the variety of antibodies with the Kell system and phenotypes and their relationship to RBC abnormalities
• Currently, there are around 32 antigens relating the K and the XK system (ID: 006) with high and low-prevalence
• RBC (only) related antigens have been described where they are only on the erythroid tissues as well as tissues containing other cell types.
• K antigens are detectable as early as 10 weeks gestation at with both low and high expression that make it immunogenic where enzymes are a factor.