04 Other Blood Groups

Located on chromosome 19.

Under control of three independently inherited sets of alleles: Lele, Sese, Hh.

If inherited, Leᵃ substance is produced.

le, h, and se genes do not produce products.

Nonsecretors.

A Lewis person can be a nonsecretor (sese) and still have Leᵃ in body fluids.

The Bombay genotype (hh) cannot express the Leᵇ phenotype.

Leᵃ and Leᵇ antigens are not products of alleles and are not antithetical antigens; they are soluble antigens.

Found as glycoproteins.

Lewis antigens are passively adsorbed onto the RBC membrane.

RBCs can only adsorb glycolipids, not glycoproteins, onto their membrane.

Both Le and Se (FUT2) genes must be inherited for Leᵇ antigen to be present.

Pregnant women often lose their original Lewis phenotype, typing as Le(a-b-), but revert back to their original phenotype postpartum.

Cord blood RBCs are phenotypically Le(a-b-).

The Le(a+b+) phenotype may appear transiently in children as they grow.

The correct or true Lewis phenotype may not be obtained until 2-3 years of age.

Abnormal lipid metabolism can cause the loss of Lewis antigen expression on RBCs.

Loss of Lewis antigen expression can be seen in:

Cancer

Alcoholic cirrhosis

Some infections

Usually IgM, but in rare cases can also be IgG.

Agglutination is observed at IS (Immediate Spin) or RT (Room Temperature) test phases but can carry over to 37°C and AHG test phases.

Agglutination is often fragile and easily dispersed.

Hemolysis may occur in-vitro, especially in fresh serum samples, because Le Abs can efficiently bind C' (complement).

When hemolytic properties are demonstrated, Le antigen-negative blood must be used.

Use commercially-prepared Le substance or Lewis-positive plasma to confirm the Le Ab reaction or eliminate it to identify other underlying Abs.

Usually occurs naturally in individuals with the phenotype Le(a-b-).

Other Le phenotypes rarely produce the antibody.

Enzymes enhance Le Ab activity.

Le Abs may be detected soon after pregnancy as pregnant women may temporarily become Le(a-b-).

Le Abs are usually not clinically significant.

They are usually IgM and react only at RT test phases.

They do not cause HDFN.

Lewis antigens are not developed at birth.

A Le Ab is considered clinically significant only when:

It is IgG.

It demonstrates the binding of C' (complement) causing hemolysis

Anti-Lea is found more frequently than Anti-Leb.

Anti-Leb can be classified into:

Anti-LebH: Reacts when both Leb and H antigens are present.

Anti-LebL: Reacts with Leb regardless of ABO type.

P1 gene on chromosome 22 produces P1 antigen.

GLOB gene on chromosome 3 produces the P antigen.

Pk gene on chromosome 22 produces the Pk antigen.

The LKE antigen is dependent on the terminal N-neuraminic acid, and the expression of LKE and Pk antigens are inversely related.

RBCs possess the P₁ and P antigens.

Lacks P₁, P, and Pk antigens.

Produces naturally occurring antibodies anti-P₁, anti-P, and anti-Pk (formerly known as anti-Tj(a-)).

RBCs express P₁ and Pk antigens, but lack the P antigen.

Typically produces anti-P antibodies.

RBCs express only the Pk antigen, with the P₁ and P antigens missing.

Can produce anti-P and anti-P₁ antibodies.

Found on most RBCs.
Antigen strength varies and decreases during storage.
A glycosphingolipid in human plasma.
A glycoprotein in hydatid cyst fluid.

Known as Globoside.
Most abundant glycolipid on RBCs.
High-incidence antigen.

High-incidence antigen.
Also found on WBCs.

Found on 98% of RBCs.

Similar to the ABO system.
Synthesized by sequential action of glycosyl-transferases which add sugars to precursor substances.

P₁: Consists of P₁ and P antigens.
P₂: Consists of only P antigen.

Similar to the A₂ subgroup.
Can produce anti-P₁.

Found in 75% of adults.

Found in the serum of P₂ people.

Naturally occurring IgM, usually clinically insignificant.

Works best at lower temperatures, with varying degrees of reactivity.

Neutralized by a reagent of Hydatid cyst fluid.

Found in P₁ᵏ individuals.

Naturally occurring IgG, clinically significant.

Causes biphasic hemolysin activity.

Found in Paroxysmal Cold Hemoglobinuria (PCH).

Autoantibody IgG with biphasic hemolysin activity; binds complement (C').

Autoantibody IgG with biphasic hemolysin activity; binds complement (C').

Also known as the Donath-Landsteiner Antibody.

Found in p individuals.

Clinically significant.

Inhibited by a reagent of Hydatid cyst fluid.

Found in p individuals

Potent hemolytic IgM antibody, binds C'

Enhanced by enzymes

Agglutinates at room temperature (RT) and hemolyzes at 37°C

Anti-P+P₁+Pᵏ (Tja) is found in ______ individuals.

Anti-P+P₁+Pᵏ is a potent hemolytic antibody of the ______ immunoglobulin class.

Anti-P+P₁+Pᵏ agglutinates at ______ and hemolyzes at ______.

Enzymes ______ the activity of Anti-P+P₁+Pᵏ.

Potent hemolytic IgM antibody that binds C'

37°C

Enzymes

Echinococcus granulosus tapeworm, fascioliasis, and bird handlers can develop anti-P₁.

Anti-PP₁Pᵏ or anti-P is linked to early abortions.

Paroxysmal Cold Hemoglobinuria (PCH) may develop with auto anti-P following viral infections.

P₁ terminal sugars serve as binding sites for E. coli, Shigella toxins, and human parvovirus B19.

Pathogenic bacterial toxins have specificity for P₁ terminal sugars.

Individuals infected with ______ tapeworm may develop anti-P₁.

Anti-PP₁Pᵏ or anti-P is associated with ______ abortions.

Following viral infections, ______ may develop with auto anti-P.

Binding sites for E. coli, Shigella toxins, and human parvovirus B19 are associated with the terminal sugars for ______.

Toxins from several ______ bacteria have binding specificity for P₁ terminal sugars.

Early abortions

PCH (Paroxysmal Cold Hemoglobinuria)

Human parvovirus B19

Formed by the action of glycosyl transferases that restructure the i antigen straight chain into a branched chain structure.

A specific gene codes for the production of glycosyl transferase.

High prevalence antigens that are oligosaccharides, differing in structure.

Wide variability exists in the strength of reactions (rxns).

I / i antigens are located on the ABH precursor.

The I / i blood group is formed by the action of ______ that restructure the i ag straight chain into a branched chain.

I / i antigens are located on the ______ precursor.

The I / i antigens are ______, but they differ in structure.

Glycosyl transferase

ABH precursor

High prevalence oligosaccharides

Newborns possess the i antigen.

Adults have I antigen, formed by the action of glycosyl transferase on the i antigen structure.

The amount of I_adult antigen is inversely proportional to the amount of i_cord antigen on the cell.

The i antigen converts to the I antigen as the child matures, typically by 18 months of age.

Rare individuals with a reduced amount of I_adult​ antigen on their cells are termed I_intermediate​.

Newborns possess the ______ antigen.

Adults have the ______ antigen, formed by glycosyl transferase action.

The i antigen is converted to the I antigen by ______ months of age.

Rare individuals with less I_adult​ antigen on their cells are termed ______.

i antigen

18 months

i_cordantigen

IgM, typically clinically insignificant.

Most individuals have a low titer I Ab that can be detected at 4°C

Detectable at room temperature (RT) and lower.

Reacts with nearly all adult RBCs, but is negative with cord blood.

that can mask underlying clinically significant alloantibodies.

I Ab is typically ______ and clinically insignificant.

Most people have a low titer I Ab detected at ______.

I Ab is usually detectable at ______ temperature or lower.

I Ab reacts with nearly all adult RBCs but is negative with ______.

A potent cold autoantibody can mask clinically significant ______.

IgM

4°C

Nearly all adult RBCs but is negative with cord blood.

It is a potent cold autoantibody masking alloantibodies.

Patients with Mycoplasma pneumoniae infections may develop cold auto anti-I.

I Ab can potentially attach C', but usually no hemolysis occurs unless it reacts at 37°C and is of high titer.

The pre-warm technique during testing can eliminate most reactivity of I Ab.

Enzymes can enhance detection of I antibodies.

I Ab is associated with Cold Agglutinin Disease (CAD) and Cold Hemagglutinin Disease (CHD), similar to Paroxysmal Cold Hemoglobinuria (PCH) where auto anti-P is present.

______ infections may lead to the development of cold auto anti-I antibodies.

Complement attachment by I Ab rarely causes ______, unless it reacts at 37°C with a high titer.

The ______ technique during testing eliminates most reactivity of I antibodies.

Enzymes can ______ the detection of I antibodies.

I Ab is associated with Cold Agglutinin Disease (CAD) and resembles conditions such as ______, where auto anti-P is present.

Mycoplasma pneumoniae

It binds complement at 37°C and is of high titer.

Pre-warm technique

Cold Agglutinin Disease (CAD)

IgM auto antibody reacts most strongly with cord cells, less with I_adult cells, and most weakly with i_adult cells.

Responsible for Warm Autoimmune Hemolytic Anemia, secondary to Hodgkin's disease.

A harmless auto antibody in the serum of A₁ and B individuals.

Reacts at different strengths with reagent cells, depending on the amount of H antigen on the RBC. For example:

O cells react stronger than A cells.

Anti-Iᴬᵀ reacts most strongly with ______ cells.

Anti-Iᴬᵀ is associated with ______, secondary to Hodgkin's disease.

Anti-IH reacts strongest with RBCs having a high amount of ______ antigen, such as O cells.

Anti-IH is considered ______ in the serum of A₁ and B individuals.

Cord cells

The amount of H antigen on RBCs

Warm Autoimmune Hemolytic Anemia

Usually an IgM antibody
Reacts at 4°C
Unlike anti-I, anti-i is not commonly seen in
healthy individuals

Rare potent anti-i can be associated with:

Infectious Mononucleosis (IM) / Epstein-
Barr Virus (EBV) infections
Some lymphoproliferative disorders

4°C

IgM

Healthy individuals

Infectious Mononucleosis

chromosome 4, producing MNSs antigens.

Due to their proximity, MNSs genes are inherited as a haplotype.

One gene codes for M or N, and the other codes for S or s.

Ns is the most commonly inherited haplotype.

GYPA codes for M & N.
GYPB codes for S & s.

MNSs antigens are carried on glycoproteins.
Most sugars contain sialic acid, forming "sialoglycoproteins."

Chromosome 4

Ns

GYPA

Sialoglycoproteins

MNSs antigens are antithetical and differ in their amino acid residues.

They are glycoproteins.

Homozygous antigens show stronger expression, while heterozygous antigens show weaker expression.

M & N antigens are destroyed by proteolytic enzymes such as ficin and papain.

Found on Glycophorin A (GPA).

Found on Glycophorin B (GPB).

Ficin and papain

Glycophorin A (GPA)

Location: On GPB, very close to the RBC membrane.

Presence: Always present when S and s
antigens are inherited.

Frequency: High frequency, occurring in 99% of the population.

Enzyme Resistance: Resistant to enzyme treatment.

Phenotype: S-s-U- individuals.

Immune Response: Can produce anti-U antibodies in response to transfusion or pregnancy.

Prevalence:
Very rare.
Found in only 1% of African Americans.
Result from a partial or complete deletion of the GYPB gene.

Extremely difficult to find.

Frequency: High-frequency antigen.

Cause: Partial or complete deletion of GPA (glycophorin A).

Confusion Potential: Can be confused with other antibodies, such as anti-Pr and anti-Wrᵇ.

Challenge: Difficult to find Enᵃ-negative RBCs for transfusion.

Cause: Near-complete deletion of GYPA and GYPB genes.

Significance: Homozygous genotype represents the null phenotype in the MNSs system.

Glycophorin A (GPA)

Near-complete deletion of GYPA and GYPB genes

Enᵃ is a high-frequency antigen.

Occurrence: Can be naturally occurring.

Special Feature: Demonstrates dosage (stronger reaction in homozygous expression).

Type: Typically IgM (rarely IgG).

Complement Binding: Does not usually bind complement (C').

Clinical Significance:
Not clinically significant if not reacting at 37°C or in AHG test phases.
Rarely implicated in Hemolytic Disease of the Fetus and Newborn (HDFN) if IgG is present.

Enzyme Activity: Will not react with enzyme-treated cells.

IgM

Are naturally occurring and demonstrate dosage.

When they are IgG.

Found more frequently than Anti-N.

Cause: Exposure to formaldehyde used in sterilizing dialysis machines, which alters M & N antigens (ags), making them appear "foreign" to the body.

Clinical Significance: Clinically insignificant.

Resolution: Usually diminishes when dialysis treatment and exposure to formaldehyde stop.

Anti-M

Exposure to formaldehyde in sterilization.

Stopping exposure to formaldehyde.

Type: IgG, clinically significant.

Optimal Reactivity: Reacts best at 37°C and in AHG test phases.

Enzyme Reactivity: Variable.

Clinical Impact: Can cause RBC destruction leading to hemolytic transfusion reactions (HTR) and hemolytic disease of the fetus and newborn (HDFN).

Reacts with S+ or s+ red cells.

Usually found in individuals with S-s- cells.

Requires U-negative RBC units for transfusion, which are extremely rare (<1% of the African American population).

Contact rare donor registries for U-negative RBCs.

IgG

S-s-

They may cause hemolytic transfusion reactions (HTR) and hemolytic disease of the fetus and newborn (HDFN).

K = Kell.

All Kell antigens are located on a glycoprotein integral to the RBC membrane.

Controlled by an autosomal

codominant gene on chromosome 7.

Sensitive to treatment with sulfhydryl agents (e.g., 2-ME, DTT, AET), which reduce disulfide bonds.

Second to the D antigen in immunogenicity.

Kell antigens are destroyed by sulfhydryl agents such as:

2-ME (2-mercaptoethanol)

DTT (dithiothreitol)

AET (2-aminoethylisothiouronium bromide)

The KELL (K) antigen gene is located on chromosome ___.

It is the second most immunogenic antigen after D.

k = Cellano
❑ High frequency ag
❑ Only 1 in 500 (0.2%) of the population is k negative

Ko / Knull phenotype

➢ Lacks all Kell ags, but expresses the related ag, Kx

➢ RBCs of Ko individuals possess elevated levels of Kx ag

➢ Sensitized individuals make anti-Ku

IgG, reacts at the AHG test phase

Can cause severe HTR

Can cause severe HDFN because Ab can destroy the erythroid precursor cells which results in the overall suppression of erythropoiesis.

Not effected by enzyme treated cells

Located on chromosome 1.

Fy locus is syntenic with Rh locus.

Fya and Fyb are codominant alleles producing Fya and Fyb antigens, respectively.

Fyx allele encodes a weakened Fyb antigen.

Fy3 is a genetic precursor to both Fya and Fyb.

Fy allele encodes no identifiable Duffy antigen.

Provides protection against malaria, specifically Plasmodium vivax infection.

The Fy locus is located on chromosome ___.

Plasmodium vivax

False (It encodes a weakened Fyb antigen).

Well-developed at birth

Destroyed by enzymes

Contributes to dosing effect

Usually IgG and react at the AHG phase.

Can cause HTR (Hemolytic Transfusion Reactions) and HDFN (Hemolytic Disease of the Fetus and Newborn).

Do not react with enzyme-treated cells.

Reactivity is enhanced in LISS (Low Ionic Strength Solution).

Anti-Fya and Anti-Fyb are typically of the immunoglobulin class ___.

They can cause HTR and HDFN.

1 → Reactivity enhancement
2 → Enzyme resistance
3 → IgG characteristics

Chromosome 18

The Kidd blood group alleles are described as ________, meaning both alleles contribute to the phenotype.

Lacks Jka, Jkb, and Jk3 antigens.

Considered as the JkJk null genotype.

May result from homozygosity for a rare silent Jk allele or the presence of the In(Jk) suppressor gene.

Produces no antigens and is considered silent

Jk antigens are well developed at birth.

Jk antigens are not denatured by enzyme treatment, but rather, treatment ________ the reactivity of Jk antibodies.

Jka

True

The Jka antigen is highly immunogenic, falling third in line after Rh(D) and K antigens.

Jk antibodies are IgG and react at the AHG test phase.

Jk antibodies can cause _______ and are frequently the causative antibody for DHTR.

Anti-Jka

True

Anti-Jka binds complement (C') and is frequently detected using poly AHG reagent.

Anti-Jk3 is found in Jk(a-b-) individuals and is an "inseparable" anti-__________.

located on chromosome 19.

The Lutheran alleles are ________

The antigens have high and low frequencies and antibodies are rarely found

True

Lu(a-b-) phenotype is seen in:
Dominant Type Lu(a-b-)
Recessive Type Lu(a-b-)
Recessive X-linked Inhibitor Type

The Lutheran phenotype Lu(a-b-) can be caused by _________ inheritance.

Lutheran antigens are produced by allelic codominant genes.

The Lutheran antigens are _______-developed at birth.

Lu^a antigen is very low frequency, while Lu^b antigen is very high frequency

True

Lutheran glycoproteins are found on the placental tissue.

The Lutheran blood group system is characterized by Lu^a as a ______ frequency antigen and Lu^b as a ______ frequency antigen.

IgM antibody

Reacts best at room temperature (RT)

Capable of binding complement (C')

May show mixed-field (mf) agglutination

Anti-Lu^b is most commonly an ______ antibody reacting at the 37°C and AHG test phases.

Anti-Lu^b

True

Can cause shortened survival of transfused cells

Associated with post-transfusion jaundice

Severe or acute hemolysis is rare

Anti-Lu3 recognizes the ______ common antigen present whenever Lu^a or Lu^b antigens are expressed.

It reacts best at RT and may show mf agglutination

A term used to describe antigens that occur in >98% of the population.

These antigens are marked with a "+" designation on an antibody identification (Ab ID) panel antigram.

A High Prevalence Antigen is also known as a ________.

>98%

False (They are marked as "+")

term used to describe antigens that occur in <10% of the population.

These antigens are marked with "0" or very few "+" designations on an antibody identification (Ab ID) panel antigram.

A Low Prevalence Antigen is also known as a ________.

<10%

True