[202x2] Chapter 4: ABO and H Blood Group Systems and Secretor Status

Explain Landsteiner's rule

*healthy individuals possess ABO antibodies to the ABO blood group antigens absent from their RBCs*.

Determine the possible ABO genotypes with an ABO phenotype

A = AA or AO. B = BB or BO. AB = AB. O = OO.

List the cells, body fluids, and secretions where ABO antigens can be located

ABO antigens can be intrinsic to the RBC membrane or soluble body fluids secretions (saliva, breast milk, synovial fluid).

Describe the ABO blood group system antibodies with regard to immunoglobulin class, clinical significance, and in vitro serologic reactions

Blood Group/Antibodies/Antibody Class: - A/Anti-B/IgM (some IgG). - B/Anti-A/IgM (some IgG). - O/Anti-A, Anti-B, Anti-A,B/Mostly IgG.

Describe the relationships among the ABO, H, and Se genes

Genes at 3 separate loci influence the occurrence and location of ABO antigens: ABO, H, Se. • The presence or absence of the A,B,H *antigens on the RBC* membrane is controlled by the *H gene*. • The presence or absence of the ABH *antigens in secretions* is influenced by the *Se gene*. H gene → H and h alleles (h is an amorph). The Bombay phenotype lacks the H antigen (hh). Se gene → Se and se alleles (se is an amorph). ABO genes → A, B, and O alleles.

Describe the formation of the H antigen from the gene product and its relationship to ABO antigen expression

H gene codes for carbohydrate building blocks on RBC membrane or secretions. • The "A" gene codes for a *transferase* that adds the immunodominant sugar, Nacetylgalactosamine, to the terminal sugar of the H antigen. -- Gene Product: N-acetylgalactosaminyltransferase. • The "B" gene codes for a transferase that adds the immunodominant sugar, D-galactose, to the terminal sugar of the H antigen. --- Gene Product: D-galactosyltransferase. • The "O" gene possesses many nonfunctional H antigens. ---- Gene Product (inactivated, nonfunctional): L-fucose.

another description of relationships among the ABO, H, and Se genes

H gene produces glycotransferases (carbohydrate building blocks), which go on to form ABO RBC antigens. Se gene allows secretion of H gene in body fluids; antibodies will be present.

List the glycosyltransferases and the immunodominant sugars for the B alleles.

Immunodominant sugar: D-galactose. Gene Product: D-galactosyltransferase.

List the glycosyltransferases and the immunodominant sugars for the A allele

Immunodominant sugar: N-acetylgalactosamine. Gene Product: N-acetylgalactosaminyltransferase.

List the glycosyltransferases and the immunodominant sugars for the O allele

L-fuctose does not express any final accepter molecule. Group O individuals have many H antigen sites because they have no A or B antigens.

List the glycosyltransferases and the immunodominant sugars for the H allele

L-fuctose. Group O individuals have many H antigen sites because they have no A or B antigens.

Discuss the selection of whole blood, red blood cell, and plasma products for transfusions

RBC transfusion: O is universal donor. AB is universal acceptor. Antigens on membrane of A and B. Plasma transfusion: AB is universal donor. O is universal receiver. Antibodies in plasma. O has both, AB has neither. Whole blood is type specific; both RBCs and plasma are being transfused.

Compare and contrast the A1 and A2 phenotypes with regard to antigen structure and serologic testing

The 2 main subgroups of A are A1 and A2 - Both react strongly with reagent anti-A (3+ to 4+). - To distinguish A1 from A2 red cells, the *lectin Dolichos biflorus is used* (anti-A1). -- *Agglutinates with A1*. -- *Does not agglutinate with A2*. - 80% of A or AB individuals are subgroup A1. - 20% are A2 and A2B. - If A2 is given to A1, hemolytic reaction occurs.

Plasma Transfusion: Universal Donor, Universal Recipient.

Universal Donor: Group AB. Universal Recipient: Group O.

RBC Transfusion: Universal Donor, Universal Recipient.

Universal Donor: Group O. Universal Recipient: Group AB

Describe how to differentiate among A3, Ax, and Ael subgroups by serologic testing

• A rare subgroup of the A type may be present if: - Weak or no agglutination with commercial anti-A and anti-A,B occurs. - Anti-A1 is present (A3, Ax, Ael). - Anti-H (ulex europaeus) causes strong agglutination. - A3 demonstrates mixed-field agglutination patterns.

Define a blood group system with regard to blood group antigens and their inheritance

• ABO antigens can be intrinsic to the RBC membrane or body secretions. • ABO antigens are detected in the embryo as early as 5 to 6 weeks' gestation. Newborns' RBCs have fewer numbers and partially developed antigens. Full expression occurs at about 2 to 4 years of age. • Dependent up on H, Se, and ABO alleles.

Describe ABO discrepancies caused by extra reactions in serum testing and how they can be resolved

• Acquired B: Test with autologous RBCs (will be negative). • B(A) phenotype: Test with monoclonal anti-A from other manufacturers. • Subgroup of A: Extend incubation or repeat with anti-A,B. • Group B transfused with group O RBCs: Check transfusion history. • Group A2 with anti-A1: Test with anti-A1; test with 3 A1 and A2 cells. • Cold autoantibody or alloantibody: Perform antibody screen with *autocontrol*. • Rouleaux: *Saline replacement*. • Weak or missing antibodies: Incubate at RT for 15 minutes or at 5°C for 5 minutes.

Discuss the Bombay phenotype with regard to genetic pathway, serologic reactions, and transfusion implications

• First reported in 1952 in Bombay, India. • RBCs lack the H antigen; is hh. • The h gene is an amorph and results in little to no production of L-fucosyltransferase. • Typing labels patients as group O individuals (no H, no A, no B). • *Patients' serum contains anti-H, anti-A, anti-B*. • Transfusion: -- Group O RBCs cannot be given, because the H antigen is present -- Only autologous units or rare donor files can be used.

Define the acquired B antigen and B(A) phenotypes; discuss the ABO discrepancies that would result from these phenotypes and methods used in resolving these discrepancies

• Group A with acquired B: - The group A immunodominant sugar is altered by a bacterial *deacetylating* enzyme. - Resembles group B and cross-reacts with anti-B. • B(A) phenotype: - Mechanism is similar to that of acquired B; however, patient is group B. • Polyagglutination: - A hidden antigen on the RBCs is exposed and reacts with most human sera. • Nonspecific aggregation causes: - Rouleaux: abnormal amounts of serum protein. - Wharton's jelly: gelatinous tissue contaminant in cord blood.

List reasons for missing or weakly expressed ABO antigens and the test methods used to resolve these discrepancies

• Show weak or negative agglutination in the reverse phase of testing. • Reactions may be explained by investigating the patient history, age, diagnosis, and immunoglobulin levels. - Newborns and elderly people have reduced antibodies. - Pathologic states that lower immunoglobulin levels.

secretor gene

• Two allele genes at this locus: Se and se. • Se is responsible for H substance in body secretions (e.g., saliva). - H is converted to A or B by glycosyltransferases. • 80% of the population are secretors: SeSe (homozygous). - 20% are nonsecretors: (sese) Sese (heterozygous).

Differentiate between type 1 and type 2 oligosaccharide structures and state where each is located

• Type 1 chain produces antibodies in secretions. • Type 2 chain produces antibodies on RBC membrane.

oligosaccharide chain

• a basic precursor structure for several RBC antigens (including A, B, and H). • attached to a protein or lipid carrier molecule.