Blood Group Systems

SEM 423
COLLEGE OF MEDICAL LABORATORY SCIENCE
OUR LADY OF FATIMA UNIVERSITY

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ABO Blood Group System
 1901 – ABO
Historical Perspective discovered

• Karl Landsteiner – Discovery of

the first human blood group
system.
• First to conduct reverse and
Forward typing
• ABO Blood group
• I gene – code for the ABO
allele’s:
• 1. IA
• 2. IB
• 3. i
Formation of A, B and H Red cell
antigen

• Formation of ABH antigen results from the

interaction of genes of three separate loci
(ABO, Hh and Se).

• These genes do not actually code for the

production of antigens but rather produce
specific glycosyltransferase that add sugars to
a basic presursor called Paragloboside or
glycan.
Ø H GENE:
ü Is needed for the formation of A and B genes; without the H gene, A and B
genes will not be coded
ü Most people are homozygous HH
ü The genotype (hh) is extremely rare and is referred to as the: Bombay
phenotype

Ø H ANTIGEN:
ü Antigen that is being converted by A and B genes; antigen needed in the
production
ü A gene: A antigen

ü B gene: B antigen

Ø Since the O gene is amorphic/silent, no conversion takes place, therefor the H

antigen is found in highest concentration in Type O individuals
Ø Amount of H-antigen/reaction with anti-H: O > A2 > B > A2B > A1 > A1B
Ø ABH antigens in the plasma: derived from both Type I and II precursor
substances

Ø The terminal sugar that attaches to the D-galactose of the precursor

substance determines the antigen
Formation of A, B and H Red cell
antigen
• H antigen – precursor structure on which A and B
antigen are made

• H and Se genes- located chromosome 19

- Not part of ABO blood group system

• ABO gene –located chromosome 9

 Formation of A, B and H Red cell
antigen
The precursor substance on erythrocytes is referred
• Type 2 precursor substance
- Means that the terminal galactose on the
precursor substance is attached to the N-
acetylglucosamine in a beta 1-4 linkage

• Type 1 precursor substance

- Means that the terminal galactose on the
precursor substance is attached to the N-
acetylglucosamine in a beta 1-3 linkage
 ABH ANTIGENS
Ø Red cell ABH antigens constists of 80 glycyoproteins and 20% glycolipids
(from type II precursors)

Ø Plasma ABH antigens consist predominantly of glycolipids (from type I

precursors)

Ø The H antigen (precursor of A and B antigen) is formed by the addition of

L-fucose to the terminal galactose on either Type I or Type II precursors

Ø A or B antigen specificity is determined by the addition of a sugar to the

terminal galactose of the H antigen/substance
• A antigen: addition of the sugar N-acetyl-D-galactosamine to the
terminal galactose of the H substance
• B antigen: addition of the sugar D-galactose to the terminal galactose
of the H substance
 STRUCTURE OF TYPE 1 AND 2 PRECURSOR SUBSTANCES:
¢ TYPE 1 PRECURSOR SUBSTANCE
¢ ABH soluble antigens/substances in secretions

Paragloboside/glycan

Glucose

D-galactose

N-acetylglucosamine
1-3 linkage
D-galactose
¢ TYPE 2 PRECURSOR SUBSTANCE

Ø ABH antigens on the RBC membrane

 STRUCTURE OF ABH ANTIGENS

Ø IF FORMED ON TYPE 1 PRECURSOR SUBSTANCE: ABH soluble

substances/antigens on secretions

Ø IF FORMED ON TYPE 2 PRECURSOR SUBSTANCE: ABH antigens on the RBC

membrane
H ANTIGEN

α-2-L-
fucosyltransferase

L-fucose L-fucose, will

attached to
TYPE 2 PS
 A ANTIGEN

A gene codes for the production of α-3-

N-Acetylgalactosaminyltransferase

Will attached to the

H antigen to
N-Acetylgalactosamine expressed A
antigen
B ANTIGEN

B genes code for the

D-galactose will
attached to H antigen
production of α-3-D-
to expressed B
galactosyltransferase
Antigen
GENE GLYCOSYLTRANSF IMMUNODOMINA ANTIGEN
ERASE NT SUGAR

H gene Alpha-2-L- L-fucose H antigen

fucosyltransferase
A gene Alpha-3-N- N-acetyl-D- A antigen
acetylgalactosaminyltr galactosamine
ansferase (GALNAC)

B gene Alpha-3-D- D-galactose B antigen

galatosyltransferase

AB gene Both Both AB antigen

0 gene None None Unchanged H

antigen
SECRETOR GENES (SE GENE)

1. The Se gene controls the presence of A, B, H antigens in saliva, sweat,

tears, breast milk, urine and semen

2. The inheritance of the Se gene codes for the production of a transferase

(alpha-2-L-fucosyltransferase) that modifies the TYPE I PRECURSOR
SUBSTANCE in secretions to form the H substance

3. 3 genotypes: SeSe, Sese, sese

• Secretors: SeSe, Sese (80%)
• Non-secretors: sese (20%)
4. An individual secretor status can be determined by testing for ABH soluble
substances in saliva

5. Other blood group substances are also secreted in plasma, and saliva but
presence is not controlled by the Se gene
 ABH antigens (RBC) ABH soluble substances
(secretions)

RBC antigens can be Soluble substances are

glycolipids, glycoproteins, glycoproteins
glycosphingolipids

Synthesized only on Type II Synthesized on Type I precursor

precursor substance substance

Type II chains refers to a beta Type I chains refers to beta 1-3

1-4 linkage linkage

Enzyme produced by H gene Enzyme produced by Se gene acts

acts of Type II chains of Type I chains
 CHARACTERISTICS OF ABO ANTIBODIES

1. Not normally present at birth. If present at birth, they originated from the
mother through placental leakage during delivery
2. They develop 3-6 months after birth

3. Predominantly IgM and react at room temperature or colder

4. Occur in two forms:

ü Naturally occurring antibodies
ü Immune antibodies produced during incompatible transfusion or
incompatible pregnancies
5. They are present in some animals and plants as lectins. Lectins are plants or
seed extracts diluted to agglutinate specific human blood group antigens
ü Dolichos biflorus: agglutinates A1 or A1B cells (anti-A1 lectin)
ü Bandeiraea simplicifolia: agglutinates B cells (anti-B lectin)
ü Ulex europaeus: agglutinates O cells (H specificity) and other ABO blood
groups depending on the amount of H antigen (anti-H lectin)

6. Present in low titer or even absent in cases of acquired and congenital

hypogammaglobulinemia and agamma globuleniemia
 ABO ANTIBODIES
IgM anti-A and anti-B IgG anti-A, anti-A, and anti-A,B

Cold reacting Warm reacting

o
Best at room temperature or Best react at 37 C
colder
Do not cross the placenta Can cross the placenta

Not indicated by HDN Indicated by HDN

Naturally occurring Immune antibodies (produced

during incompatible transplant,
pregnancy, and blood transfusion)
ABO Subgroups

• Presence of A
subgroups and B
subgroups

• Weaker serologic
reactivity of ABO
subgroups is attributed
to the decreased
number of A and B
antigen sites
A Subgroups
• 1911, Von Dungern described two different A antigens
based on reactions between group A RBC’s with Anti-A and
Anti-A1
• Subgroups: Blood type A1 and A2
• Used Lectin extract: Dolichos biflorus
PHENO REAGENTS ANTIBODIES IN SERUM OTHERS
TYPE
Anti Anti Anti- Anti-A,B Common Unexpected Subs Number of
-A -A1 B present in antigen
saliva of sites
secretors
A1 + + 0 + Anti-B None A, H 810,000-
(80%) 1,170,000

A2 + 0 0 + Anti-B Anti-A1 (1-8% A, H 240,000-

(20%) of cases) 290,000
WEAK A SUBGROUPS

Ø Subgroups weaker than A2 occur infrequently

and are most often recognized through ABO
discrepancy

Ø Make up 1% of encountered A subgroups; mainly

of academic interest

Ø Subgroups are:

ü Weak agglutination: A3, Ax, Aend

ü No agglutination: Am, Ay, Ael
Weak A Subgroups A3 weak subgroups

• A3 – demonstrate mixed-field pattern

Agglutination w/ Anti-A and Anti-A,B
• Weak expression:
α-3-N-Acetylgalactosaminyltransferase
• Anti-A1 may be present in the serum
• A substance is detected in the saliva
 Weak A Subgroups Ax weak subgroups

• Ax – not agglutinated by Anti-A reagent, but

agglutinated by most Anti-A,B
• No detectable:
α-3-N-Acetylgalactosaminyltransferase
• Produce Anti-A1 in the serum
• Caution should be used in interpreting results
of secretor studies using Ax indicator cells and
anti-A, because not all Ax cells are
agglutinated by anti-A.
 Aend weak
Weak A Subgroups subgroups

• Aend - RBCs charateristically demonstrate

mixed-field agglutination with anti-A and anti-
A,B, but only a very small percentage of the
RBCs (≤10 percent) agglutinate.

• No detectable:
α-3-N-Acetylgalactosaminyltransferase
Weak A Subgroups Am weak subgroups

• Am RBCs are characteristically not agglutinated,

or agglutinated only weakly, by anti-A or anti-
A,B.

• Normal quantities of A and H substance are

found in the saliva of Am secretors
Weak A Subgroups Ay weak subgroups

• Ay RBCs are not agglutinated by anti-A or anti-

A,B.

• Adsorption and elution of anti-A is the method

used to confirm the presence of A antigens

• Trace amount of:

α-3-N-Acetylgalactosaminyltransferase
Weak A Subgroups Ael weak subgroups

• Ael RBCs typically are unagglutinated by anti-A

or anti-A,B; however, adsorption and elution
can be used to demonstrate the presence of
the A antigen.

• produce an anti-A1 that is reactive with A1 cells

and sometimes produce anti-A, which
agglutinates A2 RBCs.
B Subgroups
B Subgroups

• Very rare and much less frequent than A

subgroups.

• Usually recognized by variations in the strength

of the reaction using anti-B and anti-A,B

• Inheritance of B subroups is considered to be a

result of alternate alleles at the B locus
 Criteria for differentiation of
weak b phenotype
• Strength and type of agglutination with anti-B,
anti-A,B and anti-H
• Presence or absence of ABO isoagglutinationin the
serum
• Adsorption-elution studies with anti-B
• Presence of B substance in saliva
• Molecular testing
Weak B Subgroups B3 weak subgroups

• Inheritance of rare gene at the ABO locus

• Anti-B and anti-A,B - Characterized by mixed-
field pattern of Agglutination
• B glycosyltransferase – present in serum, but
not in RBC membrane
• Anti-B – absent in the serum
• B substance – present in saliva and secretion
Weak B Subgroups Bx weak subgroups

• Weak agglutination with anti-B and anti-A,B

antisera.

• B glycosyltransferase – not detected in the

serum and RBC membrane

• Secretors studies – demonstrate large amount of

H substance and some B substance in saliva
Weak B Subgroups Bm weak subgroups

• Unagglutinated in Anti-B and Anti-A,B (frequent

in Japan)
• B glycosyltransferase - present in the serum
• Demonstrate small activity in B transferase
• Anti-B - not characteristically present in the
serum
• Normal quantity – H and B substance
 Weak B Subgroups Bel weak subgroups

• Unagglutinated in Anti-B and Anti-A,B

• Extremely rare phenotype, must be adsorb and elute

• B glycosyltransferase – not detected in the serum

• Inherited as a unique mutation in exon 7 of the B gene at

the ABO locus

• H substance present in the saliva

BOMBAY PHENOTYPE
and PARA-BOMBAY
PHENOTYPE
 Bombay Phenotype

• First reported by Bhende in 1952 in Bombay, India

• Represent the inheritance of a double dose of the hh

antigen

• Geneotype: hh (very rare), ABO cannot be expressed and

ABH antigens cannot be found

• 130 Bombay phenotype (in various part of the world)

Confirmation of Bombay
phenotype

• Anti-H lectin (Ulex europaeus)

• Blood type O: will agglutinate because of the

presence of H antigen
• Bombay Phenotype: will not agglutinate
because of the absence of H antigen
 Bombay Phenotype

• SERUM: contains Anti-A, Anti-B, Anti-A,B and Anti-H

• Anti-H – very potent, IgM can cause RBC lysis

• Saliva: not a secretor

• OhA, OhB, and OhAB

 PARA-BOMBAY Phenotype

• Devoid of H antigens or have small amount of H

antigen present.

• Weakly express A antigen and B antigen; detected

through adsorption and elution

• Ah, Bh. And ABh

 Rh blood group
–
™ Refers to a specific red blood cell antigen (D),
currently composed of over 50 different antigenic
specificities

™ Second most important blood group system in terms

of transfusion, as Rh system antigens are very
immunogenic

™ Produce significant HDN and HTR

 History
–
™ 1939 – Philip Levine discovered Rh Blood group
system

™ Levine found out that Rh Antibody were main cause

of HDN (Hemolytic Disease of the New born)/
Erythroblastosis fetalis

™ One year later, Landsteiner and Wiener reported on

an antibody made by guinea pigs and rabbits when
they were transfused with Rhesus macaque
monkey’s RBC
 History
–
™ Rh antibody – agglutinated 85% of Human RBC’s
Was named as Rh. (Rhesus monkey)

™ Anti-Rh produced by animals was renamed as Anti-

LW. Since Landsteiner and Wiener discovered it in
the animals.
 Nomenclature
–
™ FISCHER-RACE - DCE Terminology

™ WEINER - Rh-Hr Terminology

™ ROSENFIELD - Alphaneumeric Terminology

™ International Society of Blood Transfusion (ISBT) –

Updated Numeric Terminology
 Fisher-Race: DCE
Terminology
–
™ 1940, Fisher and Race investigate the antigen in
human. Including newly defined Rh Antigen

™ There are 3 closely linked allele discovered, Each

antigen and corresponding gene were given the
same letter designation

™ Antigens of Rh system (D, d, C, c, E, and e)

 Fisher-Race: DCE
Terminology
–
™ Each person inherits a set of Rh genes from each
parents (i.e one D or d, C or c and E or e)

™ In very rare instances, an individual may fail to

express any allelic antigen at one or both Rh loci

™ D positive antigen with lacking E or e or all CcEe

antigen

™ Deletion of phenotype: D- -, D- -, or D-
 Fisher-Race: DCE
Terminology
–
™ Rhnull – person expressing no Rh antigens on the
RBC (phenotype ___/___).

™ Rhmod – person expressing weakened phenotype;

writtens as (D), (C), and (e).
 Weiner: Rh-Hr
Terminology
–
™ Defined as Rh that produced an agglutinogen
containing a series of blood factors.

™ According to Weiner , this Rh gene produced at least

three factors within an agglutinogen.

™ Agglutinogen may be considered the phenotypic

expression of the haplotype
Weiner: Rh-Hr
Terminology
–
Weiner: Rh-Hr
Terminology
–
dCe/dCE à r’ry
Dce/dce à R0r
Rosenfield: Alphanumeric
Terminology
–
™ Rosenfield and associates proposed a system that
assigns a number to each antigen of the Rh system in
order of its discovery or recognized relationship.

™ This simply implies the presence or absence of the

antigen on the RBC.

™ Minus sign preceding the a number designates the

absence of the antigen
Rosenfield: Alphanumeric
Terminology
–
FISHER RACE ROSENFIELD

D DCe/DCe à Rh: 1,2,-3,-4,5 Rh1

C Rh2

E Rh3

c Rh4

e Rh5
 Examples:
–
Wiener Fisher-Race Rosenfield

R1r DCe/ce Rh:1, 2, –3, 4, 5

R1R2 DCe/DcE Rh:1, 2, 3, 4, 5

rr Ce/ce Rh: –1, 2, –3, 4, 5

Rzr DCE/ce Rh:1, 2, 3, 4, 5

International Society of Blood Transfusion
(ISBT) – Updated Numeric Terminology

–
™ Mandates was establish a uniform nomenclature that
is both eye and machine readable and is keeping
with the genetic basis of blood groups

™ ISBT adopted a six-digit number for each

authenticated antigen belonging to a blood group
system

™ First three number: represent the system (004)

™ Remaining three number: Antigenic Specificity
International Society of Blood Transfusion
(ISBT) – Updated Numeric Terminology
–
Fisher-Race ISBT

D ISBT 004-001

C ISBT 004-002

E ISBT 004-003

c ISBT 004-004

e ISBT 004-005
 Weak D: Variations of D Antigen
Expression
–
™ Rh Positive individuals, possess a weaker amount of
D antigen referred as Du Phenotype

™ Du Phenotype – produces anti-D

 Genetic weak D
–
™ Weak D - inheritance of D genes that code for a
weakened expression of the D antigen.

™ The D antigens expressed appear to be complete but

few in number.

™ The genetic weak D is rare and seldom found in

whites
 Partial D (D Mosaic)
–
™ D antigen expression can be weakened is when one
or more of the D epitopes within the entire D protein
is either missing and/or is altered.

™ Usually type weaker than expected or may not react

at all when routine procedures are used with most
commercial anti-D reagents
OTHER Blood
Group system
Lewis System ISBT (007)

u Not intrinsic to RBC, but are on type 1

glycosphingolipids that are passively adsorbed
the onto the RBC membrane from the plasma
u Lewis gene (Le) codes for the production of
Fucosyltransferase enzyme
u Reported by: Mourant in 1946
a b
u Antibody: Anti-Le and Anti-Le
u ISBT: 007
Lewis System

u System symbol: LE
a b
u Antigen: Le and Le
u (Le, FUT3) gene – codes for Lewis antigen,
located at chromosome 19
u (Se, FUT2) gene – codes for secretors
Antigens
u Le (a+b-)
u RBC’s are from ABH non-secretors
u Le (a-b+)
u RBC’s are from ABH secretors
u Le (a-b-)
u Either secretors or non-secretors
u Frequently found in African
u Le (a+b+)
u Phenotype is rare among whites, but frequent
among Asian’s
Lewis Antigens
u Not expressed on cord RBC
u Often diminished on mother’s RBC during
pregnancy
u Found in lymphocytes and platelets
u Other tissue: Pancreas, stomach, intestine,
skeletal muscle, renal cortex and adrenal
glands
u Found in saliva as: glycoproteins
Lewis Antibodies

u Mostly IgM; do not cross placenta

u Considered naturally occuring
u Do not cause Hemolytic disease of fetus
and Newborn
u Agglutinate in Saline suspended RBC
u Can activate the complement and cause
in vivo and in vitro hemolysis
 a
Anti- Le

u Most commonly encountered of the Lewis

antibodies
u Often detected at room temperature but
sometimes at 37C
u Rare cause of HTR’s
 b
Anti-Le

u Not common or generally as strong as

a
anti-Le
u Usually IgM; can bind complement
u Made by Le(a+b-)
 Lewis System
Genotype Substance Red Cell
Phenotype
1. ABH, lele, sese NONE Le (a-b-)

2. ABH, lele, Sese/sese ABH Le (a-b-)

3. ABH, Lele/LeLe, sese Lea Le (a+b-)

a b
4. ABH, Lele/Lele, Sese ABH, Le Le Le (a-b+)
P Blood group System (003)
u Introduced in 1927 by Landsteiner and Levine
u They injected rabbits w/ human RBC’s (initially
produced Anti-P
u P1, P or Pk
- Maybe found on RBC’s, Lymphocytes,
granulocytes and Monocytes
u P
- Platelets, epithelial cells, fibroblasts
u P and Pk
--
Plasma as glycosphingolipids
- Hydatid cyst fluid: glycoprotein
P1 Antigen
u Poorly expressed at birth
u May take up 7 years to be fully expressed
u Found on fetal red cells as early as 12 weeks but weakens
with gestational age
u Strength may vary w/ race
u Blacks stronger expression than white
u Deteriorates rapidly on storage
u P1-like substance has been found in plasma and
droppings of pigeons and turtledoves, as well as in the
egg white of turtledoves
u P1 substance has been identified in hydatid cyst fluid,
extracts of Lumbricoides terrestris (common earthworm)
and Ascaris suum
Anti-P1
u Naturally occurring IgM Ab in the sera of P2
individuals
u Found in P1- individuals
u Weak, cold reactive saline agglutinins
u React at 4C
u bind w/ complement
u Strong Anti-P1 was observed in individuals infected
with Hydatid disease
 K
Anti-PP1P
u Predominantly IgM but sometimes IgG
u Originally called Anti-Tja
- First described in the serum of Mrs. Jay
u Produced early in life w/o sensitization and reacts
w/ all RBC’s except for a person w/ p Phenotype
u Potential cause of severe HTR’s and HDFN
u Reacts over a wide thermal range
u Associated with spontaneous abortions in early
pregnancy
 K K
Anti-P (P1 and P2 )
u Naturally occurring alloantibody in the sera of all
PK individuals
u Alloanti-P is rarely seen in the blood bank, but very
significant in transfusion because it is hemolytic w/
wide thermal range of reactivity
u Anti-P specificity is found as IgG autoantibody in
patients w/PCH
u Antibody activity is biphasic, it attaches to red
cells in the cold and lyses as they warm
u Demonstrated by the Donath-Landsteiner Test
Anti- PK

u Isolated from some examples of anti-PP1PK

by selective adsorption with P1 cells
u Has been reported in the serum of P1
individuals with biliary cirrhosis and
autoimmune hemolytic anemia
I blood group system (027)

u Serum of Normal Individuals and aquired

hemolytic anemia
u With the existance of Cold agglutinins
identified by Weiner and coworkers
u Giving a name I antigen for “Individuality”
The I and I Antigens
u High prevalence antigens, but they
expressed in a reciprocal relationship
u At birth, infant RBC’s are rich in “i”;
- I is almost undetectable
u During 18 months of life, the quantity of “i”
slowly decreased as I increases until adult
portion are reached
u Adult red cells are rich in I and have only
trace amount of i antigen
Rare i Adult or Negative
phenotype

u Individuals who do not change their i

status after birth
u Ex: Hempas
Anti-I
u Commonly autoantibody that can be found
in virtually all sera
u Can be benign or pathologic
u Required testing at 4C and/or against
enzyme-treated RBC’s to detect the
reactivity
u Strong agglutination w/ adult RBC and weak
or no agglutination w/ cord or adult i RBC’s
u Not associated with HDN because the
antigen is poorly expressed on infant red cells
Pathologic Anti-I
u Potent IgM agglutinins with higher titers and
broader thermal range of activty, reacting
up to 30-32C
u Attach in vivo and cause autoagglutination
and vacsular occlusion (raynaud’s
phenomenon) or intravascular hemolysis
AUTOANTI –I
u May be stimulated by mcroorganisms
carrying I-like antigen on their surface
u Patients with Mycoplasma pneumoniae
often develop strong agglutinins with I
specificity as a cross-reactive response to
mycplasma antigen
u Listeria monocytogenes organism from a
patient with cold autoimmune hemolytic
anemia has been reported to absorb anti-I
and stimulate its production in rabbits
Anti-i
u Most autoanti-i are IgM
u Reacts best with saline-suspended cells at
4C
u Potent examples are associated with:
- Infectiuos mononucleosis
- Disease with RES
u IgG anti-i has also been described and has
been associated with HDN
The MNS (002) System
- MN Antigen
- Ss Antigen
- U phenotype
MNS System
¨ Recovered from rabbit by Landsteiner and Levine
¨ Anti-M and Anti-N

¨ 1947 – Walsh and Montgomery

¤ Discovered S antigen
¤ S antigen – genetically linked to M and N

¤ w/ antithetical partner s antigen (1951)

MN System
¨ Found in a well characterized glycoprotein called
glycophorin A

¨ Difference between the two antigen is w/in their

amino acid position 1 and 5
¨ M antigen: 1-serine and 5-glycine
¨ N antigen: 1-leucine and 5-glutamic acid

¨ Destroyed by enzyme, because MN are located at

the outer end of GPA
S and s Antigen
¨ Located on a smaller glycoprotein called
glycophorin B

¨ S and s differentiated also by their amino acid at

29 position
¨ S antigen: Methionine
¨ s antigen: Threonine

¨ Well developed at birth

¨ Easily degraded by enzyme
Antibodies
¨ Anti-M
¨ Naturally occurring saline agglutinins, reacts at 37C
¨ IgM or IgG (50%-80%)
¨ Do not bind complement
¨ Do not react with enzyme treated RBC
¨ More common in children and px w/ bacterial
infections

¨ Strong reaction: M+N-

¨ Weak reaction: M+N+
Anti-N
¨ Made by individual whose RBC’s type M+N- and
(S+ or s+)
¨ Cold reactive IgM or IgG saline agglutinin
¨ Does not bind complement or react w/ enzyme
treated RBC

¨ Reacts w/ M-N+ (can demonstrate dosage effect)

Anti-N
¨ Clinically not significant unless it reacts at 37C
¨ Cause rare, mild HDFN

¨ Disease association:
¨ Renal patients who were dialyzed on equipment
sterilized w/ formaldehyde forms Anti-Nf
f
¨ Anti-N - reacts with N+ or N-
¤ Not react at 37C
¤ Clinically insignificaant for transfusion
Anti-S and Anti-s

¨ Are IgG, reactive at 37C

¨ Exhibit dosage efffect
¨ Not react w/ enzyme-treated RBC
¨ May bind complement
¨ Cause severe HTR’s w/ hemoglobinuria and HDFN
Anti-U

¨ Formed in S- s- individuals
¨ Can also cause HDN and HTR
¨ Enhanced by enzyme treatment
The Kell (006) and Kx (019) System
- K, k - Ko phenotype
- Kpa , Kpb - Kx antigen
- Jsa , Jsb - McLeod Phenotype
Kell System
¨ Anti-k – 1949, the antithetical partner of K was
described.
a
¨ 1957 – Kp
b 1957 – discovery of null
¨ 1958 – Kp phenotype of K, designated Ko

¨ 1958 – Jsq Antibodies react w/ all RBC’s

b except those w/ the Ko
¨ 1963 - Js phenotype
Kell Blood group
¨ Not denaturated by enzyme
¨ K antigen
¤ Can be detected on fetal RBC as early as 10 weeks
and is well developed at birth
¤ Rated second only to D in immunogenecity

¨ k antigen
¤ Has been detected at 7 week
Antibodies
¨ Anti-K
¨ Most common antibody seen in the blood bank
¨ Usually IgG, reactive in the antiglobulin pahase
¨ Production was made in response to antigen
exposure through pregnancy and transfusion
¨ Severe HTR and severe HDFN
¨ Can bind complement, in vivo red cell destruction is
usually extravascular via the macrophages in the
spleen
The Duffy (008) System
a b
- Fy and Fy
- Fy3, Fy5 and Fyx
Duffy Blood Group
¨ Named after Mr. Duffy, a multiply transfused
hemophiliac
a
¨ 1950 was found to have the first described anti-Fy
¨ Fyb antigen – found in the serum of a woman who
had three pregnancies

¨ 1955 – Sanger and colleagues

¤ Reported Fy(a-b-) among African American
¤ Null phenotype was called Fy

¤ FyFy common genotype in blacks

Duffy Blood Group
¨ 1975 – Fy(a-b-)
¤ Resist infection in vitro by the monkey malaria organism
Plasmodium knowlesi
¤ Also can resist infection by Plasmodium vivax

¤ Predominant in West Africa

¤ Fy:-3 -5

¨ Fy3 and Fy5

¤ Rarely encountered
¨ Duffy symbol: FY
¨ Found in Chromosome 1
The Kidd (009) System
Kidd blood group
¨ Simple and straightforward system consisting of only
three antigens

¨ Found in the serum of Mrs. Kidd, whose infant had

HDFN

¨ The null phenotype Jk(a-b-) was described in 1959

¨ Common cause of HTR’s

¨ Designated by symbol JK or 009

 a b
Jk and Jk Ag
¨ Detected on fetal red cells as early as 11 weeks
for Jka , and 7 weeks for Jka

¨ Well developed at birth

¨ Enhanced by Enzyme
Kidd Phenotype
a b
¨ People with the null phenotype lack Jk , Jk , and
the common antigen Jk3.

¨ Although very rare, the Jk (a-b-) phenotype is most

abundant among Polynesians.

¨ It has also been found among Filipinos, Indonesians,

Chinese, and Japanese.
 a b
Anti- Jk and Anti- Jk
¨ Have notorious reputation in the blood bank
¨ Immune antibodies, made in reponse to pregnancy
or transfusion
¨ Detected in the antiglobulin test
¨ Common cause of delayed type HTR
¨ Frequent mild HDFN
¨ Methyldopa (aldomet)
Lutheran (005)
Lutheran System
a
¨ 1945 – anti-Lu was found in the serum of a
patient with lupus erythematosus

¨ The new antibody was named Lutheran for the

donor; the donor last name was Lutteran but the
donor blood sample was incorrectly labeled

b
¨ Cutbush and Chanarin described anti-Lu , which
defined the antithetical partner to Lua
 a b
Lu and Lu Ag
¨ Antigens produced by allelic codominant genes

¨ Poorly developed at birth

¨ Do not reach adult levels until age 15

 a
Anti-Lu
¨ Most are naturally occurring saline agglutinins
¨ React at 37C by indirect antiglobulin test
¨ Maybe IgA, IgM or IgG
 b
Anti-Lu
¨ Most are IgG (often IgG4) although IgM and IgA
have been noted

¨ Reactive at 37C and the antiglobulin phase

¨ Made in response to pregnancy or transfusion

¨ Inplicated with shorthened survival of transfused

cells and posttransfusion jaundice
MINOR BLOOD GROUP
DIEGO SYSTEM
ISBT (010)
DIEGO SYSTEM
• Composed of 22 antigens; 3 Independent pairs:
a b a b
▫ Antithetical antigens: Di /Di , Wr /Wr and
Wu/DISK

• Named after the first antibody marker in

Venezuelan family during investigation of HDFN
a
• 1955 – Anti-Di

• Diego antigens are carried on band 3, a major

integral RBC membrane glycoprotein
DIEGO SYSTEM
• Band 3 – also known as the red cell anion
exchanger (AE1) or solute carrier family-
4, anion exchanger, member 1 (SLC4A1).

• Located at Chromosome 17
a
• Di - rare in most population, but is
polymorphic in people of Mongoloid ancestry
Yt SYSTEM/
Cartwright Blood
group System
ISBT (011)
Yt SYSTEM
• 1956 – named the first antibody marker and
used the last letter ”t” in the patient’s last name:
“Cartwright”

a
• Yt - high prevalence
b
• Yt - low prevalence

• Three phenotype: Yt(a+b-), Yt(a+b+) common

▫ Yt(a-b+) rare
Yt SYSTEM
• Yt antigens are represented an amino acid
substitution on the
glycosylphosphatidylinositol (GPI)-linked
RBC glycoprotein acetylcholinesterase
(AChE).

• Chromosome 7

• Do not cause HDFN

Xg SYSTEM
ISBT (012)
Xg SYSTEM
• 1962 – discovered in the serum of multiply
transfused man

• High prevalence in female than male

• Controlled by X-linked gene

• Named after the X Chromosome and g “Grand

rapids” where the patient was treated
Xg SYSTEM
a
• Two antigen: Xg and CD99
a
• Xg antigen is carried by a protein with cell adhesion
properties that has been demostrated to have homology
with the CD99 molecule
• CD 99- also known as 12E7 and MIC2.
a
• Xg - located on the X chromosome at Xp22.3
• CD99 – located at Xp22.2
a
• Cord RBC express Xg weakly
a
Anti – Xg
• Usually IgG
• Sensitive to enzymes
• Not implicated in HDFN and HTR
SCIANNA SYSTEM
ISBT (013)
Scianna SYSTEM
• Sc system is composed of the three antigen:
▫ 1. Sc1 antigen
▫ 2. Sc2 antigen
▫ 3. Sc3 antigen
• Most anti-Sc1 and anti-Sc2 antibodies are IgG,
red cell stimulated and react in indirect
antiglobulin testing

• Not implicated with Hemolytic transfusion

reaction.
Scianna SYSTEM
• Anti-Sc3 is characterized as IgG, red cell
stimulated and reacting in the IAT phase of
testing.

• Linked to cause a mild transfusion reactions

• SC gene Located at chromosome 1 at 1p34

▫ the product of the gene is a protein called
erythroid memebrane associated protein
(ERMAP)
DOMBROCK SYSTEM
ISBT (014)
Dombrock SYSTEM
a b
• Antigen Do and Do
a a
• Gregory (Gy ), Holley (Hy) and Joseph (Jo )
a b
• Anti-Do and Anti-Do
▫ Described as IgG, red cell-stimulated antibodies
that react primarily in indirect antiglobulin test w/
PEG or Enzyme enhancement
▫ Not associated with HDFN
▫ Reported to cause delayed HTR
Dombrock SYSTEM
a a
• Antibodies to Gy , Hy and Jo

• all are characterized as IgG, red cell stimulated

• IAT: reactive

• Do not cause HDFN, but has been described to

cause moderate transfusion reaction
Dombrock SYSTEM

• Dombrock antigens are carried on a mono-ADP-

ribosyltransferase 4 (ART4)
▫ Attached to the RBC membrane by a GPI anchor

• Gene coding for dombrock locate at

chromosome 12
COLTON SYSTEM
ISBT (015)
Colton SYSTEM
• Composed of three antigens:
a b ab
▫ Co , Co , and Co3 (formerly Co )

• CO antigen
▫ Have been located on the transport protein known
as channel-forming integral protein (CHIP)
• CHIP
▫ Forms the primary erythrocyte water channel and
is responsible for water permeability
Colton SYSTEM
• CHIP and the Co antigen
▫ Expressed in the tissue of the proximal and
descending tubules and the collecting duct of the
kidney
▫ Account for the 80% of water reabsorption
a b
• Anti-Co and Anti-Co Associated with Acute to
delayed transfusion reactions
• Anti-Co3
▫ Causing severe HDFN
CHIDO/ROGERS
BLOOD Grp SYSTEM
ISBT (017)
CH/RG SYSTEM
• Includes 9 antigens, which are subdivided into:
▫ Six Ch antigens
▫ two Rh antigens
▫ WH antigen

• Postulated that the CH/RG antigens were

associated with human leukocyte antigen (HLA)
system
CH/RG SYSTEM
• Alleles for RG and CH have been located on two
closely linked genes known as C4A and C4B on
Chromosome 6

• Antigens product have been demonstrated on

the C4d fragments of the C4A(Rodgers) and C4B
(Chido) glycoproteins of the C4 complement
components
CH/RG SYSTEM
• Formerly, the anti-Ch/Rg were collectivelly
group as HIGH TITER, LOW-AVIDITY
(HTLA)

• Anti-Ch/Rg
▫ Stimulated usually in multi-transfused individuals
lacking one or more of the corresponding
antigens.
GERBICH
BLOOD Grp SYSTEM
ISBT (020)
Gerbich SYSTEM
• Complex system that is composed of three high
incidence and four-low incidence:

• High incidence:
▫ Ge2, Ge3 and Ge4
• Low incidence:
a a a
▫ Wb, Ls , An , and Dh
Gerbich SYSTEM
• GE antigens are inherited on chromosome 2
and are expressed on glycophorine C (GPC)
and/or glycophorine D (GPD)

• Individuals of the Leach phenotype (GE:-2,-3,-4)

present with a change in erythrocyte
morphology in the form of Elliptocyte
Gerbich SYSTEM
• Anti-GE2 and Anti-GE3
▫ Have also been noted as naturally occurring IgM
and as autoantibodies,
▫ Implicated causing acute to delayed transfusion
reactions
▫ No clinical HDFN
CROMER
BLOOD Grp SYSTEM
ISBT (021)
CROMER SYSTEM
• Composed of seven high-incidence antigens:
a a a a a
▫ Cr , Tc , Dr , Es , IFC, UMC and WES
• Three low incidence antigens:
b c b
▫ Tc , Tc , and WES

• Antigen are carried by decay accelerating factor

(DAF)
▫ Involves with the regulation of complement
activation by accelerating the decay of the C3 and
C5 convertase
CROMER SYSTEM
• Anti-CROM
▫ Are described as predominantly IgG1 (reactive in
IAT)
▫ Neutralization – may be accomplished with
concentrated serum, plasma or urine
▫ Present majority in blacks individuals
KNOPS
BLOOD Grp SYSTEM
ISBT (022)
KNOPS SYSTEM
• Composed of five antigens:
a b a a
▫ Kn (Knops), Kn , mcC (McCoy), Si , and
a
Yk (York)

• Alleles for the KN blood group have been located

on chromosome1, with the antigens residing on
complement receptor one (CR1)

• Mrs Knops
KNOPS SYSTEM
• KN antibodies
▫ Are characterized as IgG
▫ Weakly reacting in IAT
▫ Not associated with HDFN or HTR

• Helgeson Phenotype
▫ Represents the serologic null phenotype for the
knops blood group
INDIAN
BLOOD Grp SYSTEM
ISBT (023)
INDIAN SYSTEM
• Composed of two antithetical antigens:
a b
▫ In and In
▫ Relatively low and high incidence, respectively

• IN antigens are carried on the hematopoietic

isoform of the CD44 marker
• CD44- known for its immune adhesion
properties

• IN antibodies (IgG), reactive (IAT)

OK
BLOOD Grp SYSTEM
ISBT (024)
OK SYSTEM
a
• Anti-Ok
▫ Identified in 1979 and named after the marker
found in Mrs. Kobutso
• Additional antigen
▫ OKGV and OK VM
• OK antigen
▫ Carried on CD147
▫ Function as receptor and adhesion molecules
OK SYSTEM
• Gene locus found at chromosome 19

• Well developed on RBCs from newborn

• Has not been reported to cause HDFN

Raph
BLOOD Grp SYSTEM
ISBT (025)
Raph SYSTEM
• MER2 (only antigen)
▫ Antigen is derived from monoclonal, and Eleanor
Roosevelt, the laboratory where the antibody was
produced
• Raph - first person with this kind of blood type
• Gene locus located at chromosome 11

• MER2 located at CD151

▫ A tetraspanin, which appears to be essential for the
assembly of basement membranes in the Kidney and
skin
Raph SYSTEM
• Three examples of Alloanti-MER2
• Found in JEWS originating from India and
living in ISRAEL
▫ With end stage renal disease
• Fourth example:
▫ Healthy, Turkish blood donor.
JOHN MILTON HAGEN
BLOOD Grp SYSTEM
ISBT (026)
JMH SYSTEM
• Anti-JMH – found in patients 50 years old and
older.

• JMH protein
▫ The GPI-linked glycoprotein CD108

• Gene located at chromosome 15

• Usually IgG (Predominantly IgG4)
• Clinically insignificant
GILL
BLOOD Grp SYSTEM
ISBT (029)
GILL SYSTEM
• 1980 – Anti-GIL was identified

• Gil antigen – found on the glycerol transporter

aquaporin 3 (AQP3)
▫ A major intrinsic protein family of water channels
▫ Located at chromosome 9
RH-Associated
Glycorpotein
BLOOD Grp SYSTEM
ISBT (030)
 Thanks!
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