ABO Blood Groups

Type A blood terminal sugar

N-acetylgalactosamine

Type B blood terminal sugar

Galactose

True or False: a person with no Lewis antigens on their RBCs is negative for the FUT3 fucosyltransferase

True

• FUT3 encodes the Lewis fucosyltransferase enzyme.

• If FUT3 is nonfunctional (i.e., they are truly FUT3-negative), then they cannot make Lewis a or b antigens at all — no matter their Secretor status.

• So:

  • FUT3-negative = no Leᵃ or Leᵇ → RBCs are Le(a-b-).

Thus, TRUE — if they lack FUT3, they will have no Lewis antigens on their RBCs.

Secretor or Non-Secretor? Lewis b

Secretor

Secretor or Non-Secretor? Lewis a

Non-secretor

Secretor percentage in population

80%

Type O Frequency

50%

Most Common to Least Common ABO Blood Types

O > A > B > AB

Type B Frequency

15%

Type A Frequency

35%

Bel

- elution

- weak anti-B may be present but B not in secretions

ABH Antigens - Soluble Substances

- Type 1 Chains

- FUT2 Enzyme produced by Se gene

ABH Antigens on RBCs

- Type 2 Chains

- FUT1 Enzyme produced by H gene

Type 1 Substance

Attached to soluble secretions in body fluids - saliva, tears, etc.

A3

Mixed field agglutination

A1

- most common antigenic expression of A

- positive with all forms of anti-A

- A1 lectin positive

Ay

- Anti-A absorbed & eluted

- Secretor demonstrate small amount of A substance in saliva

Type AB Frequency

5%

A2

- A1 lectin negative

- reacts positive with most Anti-A reagents

- single base substitution of A gene

Bombay

- still have ABO genes

- does not express antigens for ABO type

- "hh"

- non-secretor

Ael

- Anti-A absorbed & eluted

- secretors contain only H substance & no A substance in saliva

Am

- Anti-A easily absorbed & eluted

- secretors demonstrate quantities of A substance in saliva

- no agglutination with Anti-A and/or Anti-AB

Aend

- <10% red cells show very weak mixed field agglutination

- weak agglutination with Anti-A and/or Anti-AB

Bm

- normal amounts of B substance on secretions

- no Anti-B detected

- more frequent in Japan

Ax

Weak agglutination with Anti-AB only

Bx

- reacts weakly with Anti-B and Anti-AB

- makes weakly reactive Anti-B

B3

- mixed field agglutination with Anti-B and Anti-AB

- does not make Anti-B

B

Detected by bandeiraea simplicifolia lectin

Lewis Antigen Structure in Secretions

• Lea: FUT3 adds fucose to Type 1 chain (no H formation).

• Leb: FUT2 forms H, FUT3 modifies to Leb.
  
  Lea:

  Type 1 chain → FUT3 → Lea

  Leb:

  Type 1 chain → FUT2 → H → FUT3 → Leb

ABH Antigen Structure in Secretions

• Type 1 Chain: (β1-3 linkage)

• H Antigen: FUT2 adds fucose to Type 1 chain → precursor for A and B antigens.

• A Antigen: N-acetylgalactosamine added.

• B Antigen: Galactose added.

Secretor Status and Bombay Phenotype

• Bombay (hh, sese): No H antigen on RBCs or secretions; only Lea antigen present.

• Parabombay (hh, SeSe): No H on RBCs but secretions contain A/B substances.

Impact of Secretor Status on Lewis Expression

• Secretor (Se): Express Lea and Leb; Leb adsorbs onto RBCs.

• Non-Secretor (sese): Only Lea antigen secreted; Lea adsorbs onto RBCs.

Secretor Status and ABH Expression

• Secretors (SeSe/Sese): Soluble H, A, B antigens in secretions (saliva, tears, milk, etc.).

• Non-Secretors (sese): No soluble H, A, B antigens in secretions.

Clinical Significance of Lewis Antibodies

• Type: IgM, cold-reactive.

• Hemolysis: Rare; binds complement but usually not hemolytic.

• Clinical Impact: Not clinically significant for transfusion; unlike ABO antibodies.

ABO Antibodies Clinical Properties

• Type: Naturally occurring IgM.

• Hemolysis: Clinically significant; causes acute intravascular hemolysis if incompatible.

Lewis vs ABO Antibodies

Property	Lewis Antibodies	ABO Antibodies

Isotype

IgM

IgM

Reaction Temp

Cold

Cold

Clinical Significance

Minimal

High

Complement Binding

Yes

Yes

Hemolysis

Rare

Common if mismatched

Serological Testing for ABO Typing

• Forward Type: Patient RBCs + Anti-A, Anti-B, Anti-A,B reagents.

• Reverse Type: Patient plasma + A1 and B reagent cells.

Discrepancy Identification in ABO Typing

• Mismatch: Forward type ≠ Reverse type.

• Action Steps:

  • Repeat testing.

  • Classify discrepancy.

  • Apply appropriate serologic enhancement (cold incubation, wash cells, use A1 lectin).

Typical Causes of ABO Discrepancies

• Weak/missing antigen (newborn, elderly, immunocompromised).

• Unexpected antibodies (cold agglutinins, alloantibodies).

• Technical error or sample contamination.

Tools to Resolve ABO Discrepancies

• Use Anti-A,B to detect weak A.

• Use A1 lectin to differentiate A subgroups.

• Wash and warm cells to remove cold antibodies.

• Perform autocontrol and DAT if autoantibody suspected.

Red Cell Donor Compatibility — Key Concept

Safe Transfusion = Donor RBCs lack antigens against which recipient has antibodies.

Compatible Red Cell Donor Choices

Recipient Blood Type	Compatible RBCs

A

A, O

B

B, O

AB	AB, A, B, O

O

O only

Compatible Plasma Donor Choices

Recipient Blood Type	Compatible Plasma

A

A, AB

B

B, AB

AB

AB only

O	O, A, B, AB

Universal Donors and Recipients

• Universal RBC Donor: Type O negative.

• Universal Plasma Donor: Type AB plasma.

• Universal RBC Recipient: Type AB positive.

Type 1 vs Type 2 Chains

• Type 1: β1-3 linkage; found in secretions (glycoproteins).

• Type 2: β1-4 linkage; found on RBC membrane (glycolipids and glycoproteins).

Role of FUT1 and FUT2 Genes

• FUT1 (H gene): Adds fucose to Type 2 chain on RBCs → H antigen.

• FUT2 (Se gene): Adds fucose to Type 1 chain in secretions → soluble H antigen.

Lewis Phenotypes and Secretor Status

Lewis Phenotype	Secretor Status	Notes

Le(a+b-)

Non-Secretor

Lea only

Le(a-b+)

Secretor

Lea and Leb

Le(a-b-)

Lewis Null

No Lewis antigens

Le(a+b+)

Weak Secretor (mutated Se)

Rare

Bombay and Parabombay Distinction

• Bombay (hh, sese): No H, A, or B on RBCs; anti-H, anti-A, anti-B in plasma.

• Parabombay (hh, Se): No H on RBCs, but soluble A/B antigens in secretions.

Lewis Antigen Absorption on RBCs

Absorption: Lewis antigens are adsorbed from plasma onto RBCs, not genetically synthesized by RBCs.

Lewis Antibodies and Pregnancy

• Lewis antigens diminish during pregnancy.

• Transient Lewis-negative status can lead to temporary antibody formation.

Key Characteristics of Lewis Antibodies

• Form naturally.

• Commonly found in Le(a-b-) individuals.

• Enzyme treatment enhances Lewis antibody reactions.

Inhibition Testing for Secretor Status

• Principle: Saliva containing A, B, or H substances blocks antibody reactions.

• Result: No agglutination = Antigen present in saliva = Secretor.

Summary of Bombay and Parabombay Secretions

Genotype	Secretions	RBC Phenotype
hh, sese	Lea only	Bombay
hh, Se	Lea, Leb, A/B substances	Parabombay