BLOOD BANK

Other Major
Blood Groups
Asmiana A. Mategas BSMT 3-A
BLOOD BANK CHAP 8

MN or MNSs system
1927 - Landsteiner and Levine discovered from

002: The MNS the recovered antibodies in rabbits

Blood Group 1947 - Walsh and Montgomery discovered S

1951 - s was discovered
System 1953 - Weiner reported an antigen with a
high-incidence, antigen U
Greenwalt and colleagues observed that all U–
RBCs were also S–s–
M and N were antithetical antigens
Chromosome 4 46 antigens, making it equal to Rh in size
genes encoding the MNS antigens
and complexity
BLOOD BANK CHAP 8
BLOOD BANK CHAP 8
Biochemistry
GPA
carry M and N antigens
has 131 amino acids
Most O-linked carbohydrate structures are
branched tetrasaccharides containing one GalNAc,
one Gal, and two NeuNAc (sialic acid)
associates with protein band 3
expressed on renal endothelium and epithelium
GPB
carry S, s, and U antigens
has 72 amino acids
Most O-linked carbohydrate structures are
branched tetrasaccharides containing one GalNAc,
one Gal, and two NeuNAc (sialic acid)
associated with the Rh protein and Rh-associated
glycoprotein complex
expressed on renal endothelium and epithelium
BLOOD BANK CHAP 8

Biochemistry
BLOOD BANK CHAP 8

Genetics
Chromosome 4 ; 4q28-q31

GYPA GYPB GYPE

code for GPA code for GPB does not appear to make a
located at chromosome 4 at located at chromosome 4 at glycoprotein
4q28–q31 4q28–q31 participates in gene
alleles (M/N) are alleles (S/s) are rearrangements that result
codominant codominant in variant alleles
the ancestral gene, similar size and
organized into 7 exons arrangement to GYPA but has
only 5 coding exons plus 1
noncoding or pseudoexon
BLOOD BANK CHAP 8

Antigens
M and N Antigens
Determinants are carried on glycophorin A
(GPA)
M - serine at position 1 and glycine at
position 5
N - leucine at position 1 and glutamic acid at
position 5
about 106 copies of GPA per RBC
Well developed at birth
easily destroyed by ficin, papain, bromelin,
trypsin and pronase
Antibodies are heterogeneous
BLOOD BANK CHAP 8

Antigens
S and s Antigens
carried on glycophorin B (GPB)
S - has methionine at position 29 of GPB
s - has threonine at position 29 of GPB
fewer copies of GPB than GPA per RBC
about 1.5 times more copies of GPB on S+s– RBCs
than on S–s+ RBCs
Well developed at birth
Antigens are less easily degraded by enzymes
BLOOD BANK CHAP 8
MNSs Antibodies
Anti-M
Naturally occurring saline
agglutinins that react below
37°C
Do not bind complement
Do not react with enzyme-
treated RBCs
may react better with M+N–
RBCs (genotype MM) than with
M+N+ RBCs (genotype MN)
Some are pH-dependent,
reacting best at pH 6.5
rarely causes HTRs, decreased
red cell survival, or HDFN
Anti-N
similar to anti-M
a cold-reactive IgM or IgG
saline agglutinin that does
not bind complement or react
with enzyme-treated RBCs
made by individuals whose RBCs
type M+N– and S+ or s+
Rare examples are pH- or
glucose-dependent
less common than anti-M
rare cases of mild HDFN
A potent anti-N can be made by
the rare individual whose RBCs
type M+N–S–s– because they
lack both N and GPB that has
‘N’ activity
Anti-S and
Anti-s
Most are IgG, reactive at
37°C and the antiglobulin
test
seen less often than Anti-M
but are more likely to be
clinically significant
May bind complement,
associated with severe HTRs
with hemoglobinuria and HDFN
BLOOD BANK CHAP 8
GPA- and GPB- Phenotypes
3 rare phenotypes: GPA-, GPB-, both GPA- GPB- (lack all MNS antigens)
U- Phenotype
Located on GPB, between amino
acids 33 and 39
high-prevalence antigen found
on RBCs of all individuals
except about 1% of African
Americans
RBCs usually type S–s–U–
typically IgG
reported to cause severe and
fatal HTRs and HDFN
Resistant to enzyme treatment
Many examples of anti-U are
actually anti-U plus anti-GPB
En(a-) Phenotype Mk Phenotype
1969 - Darnborough, Furuhjelm and rare silent gene
colleagues discovered Ena (for 1964 - named by Metaxas and
envelope)
Metaxas-Buhler
appeared to be M–N– with reduced
do not produce M or N
NeuNAc on their RBCs
produce anti-Ena (reactivity also silent at the Ss locus
against various portions of GPA 1979 - 2 related MkMk blood
unrelated to M or N) donors were found in Japan
Anti-EnaTS M–N–S–s–U–En(a–)Wr(a–b–)
trypsin-sensitive (TS) area on represents a single, near-
GPA between amino acids 20 and
complete deletion of both
39
Anti-EnaFS
GYPA and GYPB7
ficin-sensitive (FS) area the null phenotype in the MNS
between amino acids 46 and 56 system
Anti-EnaFR
ficin-resistant (FR) area around
amino acids 62 to 72
caused severe HTRs and HDFN
BLOOD BANK CHAP 8

1927

003: P Blood Landsteiner and Levine introduced it

anti-P, that divided human RBCs into two groups: P+ and P–
Group System 1951
(P1PK), and Levine and colleagues described anti-Tja (antiPP1Pk)

028: Globoside Anti-P became anti-P1; the P+ phenotype became P1; the P–

Blood Group phenotype became P2; and the rare P null individual became p
1959
System (GLOB) Matson and coworkers described a new antigen, Pk
& related
antigens
BLOOD BANK CHAP 8

Biochemistry

Structurally related to ABO antigens and exist as

glycoproteins and glycolipids (glycosphingolipids)
There are two distinct pathways for the synthesis of
the P blood group antigens:
lactosylceramide (or Gb2, also known as ceramide
dihexose or CDH) form either paragloboside and P1 or
produce globoside series
BLOOD BANK CHAP 8

Genetics
A4GALT (alpha 1,4-galactosyltransferase)
gene encoding the enzyme (4-α-galactosyltransferase (Gb3 or Pk synthase)) responsible
for the synthesis of Pk
B3GALNT1
encoding the 3-β-Nacetylgalactosaminyltransferase (Gb4 synthase) responsible for
converting Pk to P
Several mutations in both genes have been identified that result in the p and Pk
phenotypes
A polymorphism in the Pk synthase was recently identified that ties the P1 and Pk
antigens together
P1PK gene (located at chromosome 22q11.2) and the P gene (located at chromosome
3q26.1) are inherited independently
gene for the synthesis of LKE has not yet been cloned
BLOOD BANK CHAP 8

P1 P2

P Antigens Most common

React with anti-P1 and anti-P
Poorly expressed at birth
Other most common phenotype
Do not react with anti-P1 but
do react with anti-P
Deteriorates rapidly on storage

Pk1
A very rare phenotype
P1 and Pk antigen on RBC
Have not been identified in secretions React with anti-P1 and anti-Pk
but not with anti-P
Pk2
A very rare phenotype
P2 and Pk antigen on RBCs
React with anti-Pk but not with
anti-P1 or anti-P

P null (P phenotype)
Extremely rare
RBCs are negative for P, P1, and
Pk antigen
Do not react with anti-P1, anti-
P, or anti-Pk
BLOOD BANK CHAP 8

P Antibodies
2 categories: clinically significant and potently hemolytic

Anti-P1 Anti-PP1Pk Anti-P Luke (LKE) Antigen

Naturally occurring, rarely occur (Allo Anti-P) 1965 - Tippett and
cold-reacting, IgM Originally called anti- naturally occurring colleagues; antibody in
weak, cold reactive Tja alloantibody in the the serum with
saline agglutinin First described in the sera of Pk individuals Hodgkin’s lymphoma
optimally reactive at serum of Mrs. Jay reactivity is similar 3 phenotypes:
4°C reacts with all RBCs to that of anti-PP1Pk 84% tested Luke+
Don’t bind complement except those of the p Donath-Landsteiner 14% were weakly
can be neutralized or phenotype antibody positive or Luke(w)
inhibited with soluble the anti-P, anti-P1, associated with 2% were Luke–
P1 substance and anti-Pk components Paroxysmal Cold thought to be
of anti-PP1Pk are Hemoglobinuria phenotypically related
separable through seen in patients because the antibody
adsorption with tertiary reacted with all RBCs
Associated with an syphilis except 2% of P1 and P2
increased incidence of demonstrable only by phenotypes and those
spontaneous abortions the Donath- having the rare p and
in early pregnancy Landsteiner test Pk phenotypes
BLOOD BANK CHAP 8

1956 - Wiener and coworkers; I for “individuality”

antibody reacted with most blood specimens tested
1960 - Marsh and Jenkins reported finding anti-i
027: The I I and i are not antithetical antigens

Blood Group
gene encoding the transferase that converts i active straight
chains into I active branched chains has been cloned

System synthesis of i antigen is not controlled by this same gene

BIOCHEMISTRY AND GENETICS

early association of I and i to ABH was demonstrated by complex
antibodies involving both ABH and Ii specificity
i antigen activity is defined by at least two repeating N-
acetyllactosamine [Gal(β1-4)GlcNAc(β1-3)] units in linear form
I antigen activity is associated with a branched form of i
antigen
IGnT (GCNT2) gene on chromosome 6p24 - encodes the N-
acetylglucosaminyltransferase
BLOOD BANK CHAP 8

I Antigens

Clausen and Hakomori - refer to I

and i as histoblood group antigens
i antigen has a reciprocal
relationship with I
Both are high-prevalence antigens
Both are developmentally regulated
There is no true I– or i– phenotype
BLOOD BANK CHAP 8

I Antigens

Ii I/I1 i/I2
Represent developmental Detected in saliva by A characteristic of dividing
antigens on red cells hemagglutination inhibition cells present on a variety
and in many other ID (developed) of cell types including
Most adult cells, but
tissues lymphoblasts, fibroblasts,
not cord or adult i cells
Treatment of red cells I (fetal)
erythroblasts, and
with proteases or with Expressed on all human thymocytes
sialidase generally red cells
enhances expression of IT antigen
Ii antigens named by Booth et al.
expressed strongly on
cord cells, weakly on
normal adult cells, and
weaker still on adult i
cells
T - transition
BLOOD BANK CHAP 8

Ii Antibodies
Present in the sera of all adults
potent cold lymphocytotoxins, effective at killing B and T lymphocytes

Anti-I
Most prevalent of autoantibodies
Found in virtually all sera
Generally weak
Incubating tests in the cold enhances anti-I
reactivity and helps confirm its identity
not associated with HDFN because the antibody is
IgM
Autoanti-I
production of autoanti-I may be stimulated by
microorganisms carrying I-like antigen on their
surface
Found in the serum of many normal healthy
individuals and is benign
weak, naturally occurring, saline-reactive IgM
agglutinin with a titer less than 64 at 4°C
strong autoanti-I can mimic alloanti-I
BLOOD BANK CHAP 8

Ii Antibodies
Present in the sera of all adults
potent cold lymphocytotoxins, effective at killing B and T lymphocytes

Alloanti-I Anti-I lectin

Does not react with autologous cells Lectin prepared from the gonads of Aplysia
Almost invariably IgM depilans, a marine mollusc (sea slug)
Usually only active at low temperatures behaves serologically as anti-I
BLOOD BANK CHAP 8

Ii Antibodies
Present in the sera of all adults
potent cold lymphocytotoxins, effective at killing B and T lymphocytes

Anti-i Autoanti-i
found in the serum of patients with rare antibody that gives strong reactions with
infectious mononucleosis and occasionally cord RBCs and adult i RBCs and weaker reactions
causes haemolysis with adult I RBCs
Associated with immunodeficiency Most are IgM
associated with HDFN High-titer autoantibodies with a wide thermal
range may contribute to hemolysis
BLOOD BANK CHAP 8

Ii Antibodies
Present in the sera of all adults
potent cold lymphocytotoxins, effective at killing B and T lymphocytes

Anti-IT
1965 - Curtain and coworkers; cold agglutinin in
Melanesians that did not demonstrate classical I
or i specificity
1966 - Booth and colleagues confirmed these
observations
Expressed strongly on cord cells, weakly on most
adult cells, and very weakly on adult i cells
Examples IgM and IgG anti-IT reacting
preferentially at 37°C (warm autoimmune
hemolytic anemia)
Anti-j
Reacts with protease- and sialidase-treated red
cells, but not with cells treated with endo-b-
galactosidase
Resembled most pathogenic anti-I and -i by
expressing the 9G4 idiotype, a characteristic of
antibodies encoded by a gene utilizing a V4- 34
sequence
BLOOD BANK CHAP 8

Ii Antibodies
Present in the sera of all adults
potent cold lymphocytotoxins, effective at killing B and T lymphocytes
BLOOD BANK CHAP 8

Consists of 32 high-prevalence
and low-prevalence antigens

006: The Kell first blood group system

discovered after the
Blood Group introduction of antiglobulin

System (KEL) testing

1946 - Anti-K was identified in

and 019: Kx the serum of Mrs. Kelleher

1949 - anti-k was described
Blood Group 1957 and 1958 - antithetical

System (XK) antigens Kpa and Kpb were

described
1958 and 1963 - Jsa and Jsb
were found to be antithetical
and related to the Kell system
1957 - discovery of null
phenotype, Ko
1961 - a numerical notation was
proposed for the Kell system
BLOOD BANK CHAP 8

Biochemistry

located on a glycoprotein that consists

of 731 amino acids and spans the RBC
membrane once
Kell glycoprotein is covalently linked
with another protein, called Xk, by a
single disulfide bond
The structure of the Xk protein suggests
a membrane transport protein
BLOOD BANK CHAP 8

Genetics

KEL gene, located on chromosome 7 (at 7q34), is organized into 19 exons of

coding sequence
No Kell haplotype has been shown to code for more than one low-prevalence
antigen
XK gene is independent of KEL and located on the short arm of the X
chromosome at position Xp21.1.7
BLOOD BANK CHAP 8

found only on RBCS

Only 3,500 up to 18,000 K antigen sites per RBC
Very immunogenic

KELL Xk protein
erythroid tissues, brain, lymphoid organs,

Antigens
heart, and skeletal muscle
Ko - null phenotype
Arises from homozygosity for a silent gene at
the KEL locus
Ku antigen
present on all cells
K18
only Kell antigen not shown to be inherited
TOU (KEL26)
high frequency antigen absent from Ko cells
BLOOD BANK CHAP 8

KELL Antigens
K and k Antigens Kpa, Kpb, Kpc Jsa and Jsb Kx Antigen
Antigens Antigens
rated second only to D Present on all RBCs
in immunogenicity Kpa and Kpc are low- Jsa antigen except those of the
Well developed at birth prevalence mutations of antithetical to the rare McLeod phenotype
K - 10 to 11 weeks their high-prevalence high-prevalence
k - 6 to 7 weeks’ partner Kpb antigen Jsb
gestation Kpa gene is associated Jsa and Jsb were linked
Most anti-K appear to with suppression of to the Kell system when
be induced by pregnancy other Kell antigens on it was discovered that
and transfusion the same molecule, Ko RBCs were Js(a–b–)
Antibodies to k antigen including k and Jsb
are seldom encountered Kpc antigen is even
more rare
BLOOD BANK CHAP 8
KELL Antibodies
Anti-K
anti-K is the most common
antibody seen in the blood
bank
Usually IgG and reactive in
the antiglobulin phase
made in response to antigen
exposure through pregnancy and
transfusion and can persist
for many years
Naturally occurring IgM
examples of anti-K are rare
and have been associated with
bacterial infections
Has been implicated in severe
HTRs
associated with severe HDFN
Antibodies to Kpa, Jsa, and
Other Low-Prevalence Kell
Antigens
rare
most often detected through
unexpected incompatible
crossmatches or cases of HDFN
serologic characteristics and
clinical significance of these
antibodies parallel anti-K
original anti-Kpa was naturally
occurring, but most antibodies
result from transfusion or
pregnancy
Antibodies to Kpa, Jsa,
and Other Low-Prevalence
Kell Antigens
rare
Parallel anti-K in serologic
characteristics and clinical
significance
Easy to detect but difficult to
work with
Finding compatible units for
transfusion can be difficult
BLOOD BANK CHAP 8

KELL Antibodies
Ko Phenotype Anti-Ku (K5)
Immunized individuals with the
Lack expression of all Kell Ko phenotype typically make an
antigens antibody called anti-Ku (K5)
Have no membrane abnormality Appears to be a single
and survive normally in specificity and cannot be
circulation separated into components
Rare Has caused both HDFN and HTRs
BLOOD BANK CHAP 8

The McLeod Phenotype and Syndrome

1961
Allen and coworkers
initially appeared to be Kell null but who demonstrated
weak expression of k, Kpb, and Jsb detectable by
adsorption-elution methods

KELL Very rare

RBCs lack Kx and another high prevalence antigen, Km, and

Antibodies
have marked depression of all other Kell antigens
associated with several mutations and deletions at the XK
locus
acanthocytic (having irregular shapes and protrusions)
with decreased deformability and reduced in vivo survival
have a variety of muscle and nerve disorders that,
together with the serologic and hematologic picture, are
collectively known as the McLeod syndrome
elevated serum creatinine phosphokinase levels of the MM
type
Lyon hypothesis - expression of Kx in women who are
carriers of the Mcleod phenotype
BLOOD BANK CHAP 8

1950
Named for Mr. Duffy who was found to have the first
008: Duffy described example of anti-Fya

Blood Group 1951

Fyb was found in the serum of a woman who had had three
System (FY) pregnancies
1955
Sanger and colleagues reported that the majority of
African Americans tested were Fy(a–b–)
1975
Fy(a–b–) RBCs resist infection in vitro by the monkey
malaria organism Plasmodium knowlesi
BLOOD BANK CHAP 8

Biocehmistry
reside on a glycoprotein of 336 amino acids and two N-glycosylation sites
amino acid at position 42 on Duffy glycoprotein:
Fya has glycine
Fyb has aspartic acid
BLOOD BANK CHAP 8

Genetics
1968
Duffy gene was linked to a visible, inherited
abnormality of chromosome 1
The gene is located near the centromere on the long
arm of chromosome 1 at position 1q23.2.
Duffy Blood Group Sysytem contains 4 alleles:
Fya
Fyb
Fy
Fyx
These alleles are responsible for the major
antigens and result in 4 common phenotypes:
Fy a+b+ = Ag (Fya and Fyb) Ab (none)
Fy a+b− = Ag (Fya) Ab (Anti-Fyb)
Fy a−b+ = Ag (Fyb) Ab (Anti-Fya)
Fy a−b− = Ag (none) Ab (Anti-Fya and Anti -Fyb
BLOOD BANK CHAP 8

Duffy Antigen Receptor for Chemokines

A promiscuous receptor, binds with high affinity to 60% of inflammatory chemokines from both CX and CC classes,
but not with homeostatic chemokines
2 main classes of chemokines based on the position of two highly conserved cysteine residues at their N -
termini:
CXC
CC
It also has another two minor classes:
C
CXXXC
Most chemokine receptors belong to a very large family of integral cell-membrane glycoproteins, G protein -
coupled receptors, which traverse the membrane seven times and have an extracellular N - terminal domain
Duffy - a chemokine-binding protein with no signaling function and has been referred to as a ‘silent receptor’
or interceptor (internalizing receptor)
BLOOD BANK CHAP 8

DUFFY Antigens

Most important in routine blood bank serology are Fya and Fyb
Can be identified on fetal RBCs as early as 6 weeks gestational age and are well
developed at birth
There are about 13,000 sites Fya on Fy(a+b–) and 14,000 Fyb sites on Fy(a–b+) RBCs
Have been identified in other body tissues, including brain, colon, endothelium, lung,
spleen, thyroid, thymus, and kidney cells
Result from a Gly42Asp substitution within the Duffy glycoprotein
BLOOD BANK CHAP 8

DUFFY Usually IgG and react best at the antiglobulin

Antibodies
phase
can activate complement
Because anti-Fya and anti-Fyb do not react with
enzyme-treated RBCs, this is a helpful technique
Anti-FyA when multiple antibodies are present
Anti-Fyb Have been associated with acute and delayed HTRs
Fyx Associated with HDFN that ranges from mild to
Fy3 Antigen and Antibody severe
Fy5 Antigen and Antibody Rare autoantibodies with mimicking Fya and Fyb
specificity have been reported
BLOOD BANK CHAP 8
DUFFY Antibodies
Anti-FyA
found as a single specificity
or in a mixture of antibodies
usually IgG, mostly IgG1
Occurs three times less
frequently than anti-K
commonly detected after 6
months and even more so after
5 years
Anti-Fyb
Often consisting entirely of
IgG1
20 times less common than
anti-Fya and often occurs in
combination with other
antibodies
stimulated by pregnancy and
transfusion, and by
intrauterine transfusion in
the mother
Some anti - Fyb bind
complement
Fyx
Does not produce a distinct
antigen but rather is an
inherited weak form of Fyb
that reacts with some examples
of anti-Fyb
Individuals with Fyx may type
Fy(b–), but their RBCs adsorb
and elute anti-Fyb
There is no anti-Fyx
BLOOD BANK CHAP 8

DUFFY Antibodies
Fy3 Antigen and Antibody Fy5 Antigen and
1971 - anti-Fy3 was found in the serum Antibody
Fy(a–b–)
Because it was an inseparable anti- 1973 - Colledge and coworkers
FyaFyb, it was thought to react with
discovered anti-Fy5 in the
an antigenic determinant or precursor
common to both Fya and Fyb
serum of an Fy(a–b–)
Ab molecular structure of Fy5 is
rare antibody made by Fy(a–b–) not known
individuals who lack the Duffy Expressed equally strongly on
glycoprotein red cells of adults and
present on all red cells apart
from those of the Fy(a– b–)
newborns
phenotype DARC appears to be part of a
potentially haemolytic and has protein complex that contains
been responsible for immediate and the Rh proteins
delayed HTRs , including
intravascular haemolysis in an
acute reaction and hyperhemolysis
in a patient with sickle cell
disease
BLOOD BANK CHAP 8

Fy(a– b– ) phenotype
Resistant to infection by the malarial parasite

DUFFY and Plasmodium vivax & knowlesi merozoites

Red cells are refractory to invasion by P.
Malaria vivax in vitro
Fy6 epitope - important for the invasion of P.
vivax
Despite being Fy(b+) and Fy3, red cells of the
Old World rhesus monkey are Fy– 6
New World capuchin monkey cells are Fy(a– b–)
Fy3,–6
BLOOD BANK CHAP 8

Discovered in 1950s
consisting of only three antigens
1951 - Allen and colleagues reported finding an

009: KIDD
antibody in the serum of Mrs. Kidd, whose infant
had HDFN
Blood Group anti-Jka - reacted with 77% of Bostonians

System (JK) 1953 - Its antithetical partner, Jkb, was found

1959 - null phenotype Jk(a–b–) was described in
The propositus made an antibody to a high-
prevalence antigen called Jk3
antibodies can be difficult to detect and are a
common cause of HTRs
BLOOD BANK CHAP 8

Biochemistry

1982 - Heaton and McLoughlin reported that

Jk(a–b–) RBCs resist lysis in 2M urea
Jk(a+) or Jk(b+) - within 1 minute
Jk(a–b–) - delayed by 30 minutes
predicted Kidd glycoprotein has 389 amino
acids with 10 membrane-spanning domains
and two N-glycosylation sites, one of
which is extracellular on the third
extracellular loop
glycoprotein is a urea transporter.
BLOOD BANK CHAP 8

Genetics
Jk locus is on chromosome 18 at position 18q12.3.
Gene SLC14A1
a member of the urea transporter gene family
Jka/Jkb polymorphism is associated with an amino acid
substitution at position 280
the silent Jk allele can arise from mutations in both the
Jka and Jkb alleles
BLOOD BANK CHAP 8

KIDD Antigens

Jka and Jkb

Commonly found well developed on RBCs of most individuals even neonates
Jka: 11 weeks
Jkb: 7 weeks
Not found on platelets, lymphocytes, monocytes, or granulocytes
Inherited as codominance
Not very immunogenic
Jk(a+b–) RBCs carry 14,000 antigen sites per cell
Jk(a-b-)
is generally inherited recessively and is most commonly found in Polynesians
lack the high incidence Ag Jk3, and lack the Kidd glycoprotein
BLOOD BANK CHAP 8

KIDD Antibodies
IgG and warm-reactive
LABILE in storage
Can bind with complement

Anti-JKa and Anti-Jkb Autoantibodies Jk3 Antibodies

Allantibodies Usually IgG

Monoclonal antibodies
Usually IgG or a mixture of May decline rapidly in vivo
IgM human monoclonal anti-Jka
IgG and IgM (rarely pure IgM) Has been responsible for
and -Jkb have been produced by
Anti-Jka is more frequently severe immediate and delayed
Epstein-Barr virus-
encountered than anti-Jkb HTRs
transformation of lymphocytes
Many anti-Jka react more
from immunised donors and
strongly with Jk(a+b–) than
fusion with mouse myeloma
with Jk(a+b+) cells
cells to form heterohybridomas
Many examples of the Kidd
antibodies bind complement
Anti-Jka has been responsible
for severe and fatal immediate
HTRs
Anti - Jkb has also been
incriminated in severe delayed
HTRs
BLOOD BANK CHAP 8

1945
anti-Lua was found in the serum of a patient with SLE
Named Lutheran for the donor
1956
Cutbush and Chanarin described anti-Lub

005: LUTHERAN 1961

Blood Group
Crawford and colleagues described the first Lu(a–
b–)phenotype

System (LU) 1963

the Lu(a–b–) phenotype inherited as a recessive silent
allele was described
Twenty antigens are part of the Lutheran system, numbered
through Lu22
antigens have been detected on fetal RBCs as early as 10 to
12 weeks of gestation, they are poorly developed at birth
BLOOD BANK CHAP 8

Biochemistry and Genetics

antigens are located on a type 1 transmembrane protein
The protein exists in two forms as a result of
alternative RNA splicing:
longer Lu glycoprotein
shorter basal cell adhesion molecule (B-CAM)
glycoproteins belong to the immunoglobulin superfamily
of proteins; the repeating extracellular domains are
homologous to immunoglobulin variable or constant
domains
proteins are multifunctional adhesion molecules that
bind laminin
The molecular basis for the four pairs of antithetical
antigens and several of the high-prevalence antigens has
been determined through the creation of Lutheran
glycoprotein mutants and subsequent sequencing of the
exons encoding the extracellular domains

Lu gene is located on chromosome 19 at position 19q13.2

BLOOD BANK CHAP 8

LUTHERAN Antigens

Have not been detected on

platelets, lymphocytes, monocytes,
or granulocytes
Located on two red cell membrane
glycoproteins (CD239) of apparent
MW 78 and85 kDa
Lua and Lub are antigens produced
by allelic codominant genes
Most individuals are Lu(b+); 8% of
whites and 5% of blacks are Lu(a+)
Lub sites per RBC is low
1,640 to 4,070 on Lu(a–b+) RBCs
850 to 1,820 on Lu(a+b+) RBCs
BLOOD BANK CHAP 8
LUTHERAN Antibodies
Anti-Lua
1945 - Callender et al.
described the first Lutheran
antibody, anti-Lua
Usually IgM, but, like other
Lutheran -system antibodies,
often have IgG and IgA
components
Often goes undetected in
routine testing because most
reagent RBCs are Lu(a–)
Anti-Lub
Relatively rare, often found as
a single antibody
Most are mixtures of IgG and
IgM, although IgA may also be
present
stimulated by transfusion and
by pregnancy
implicated with shortened
survival of transfused cells
and post-transfusion jaundice
Anti-Lu3
rare antibody that reacts with
all RBCs except Lu(a–b–) RBCs
Looks like inseparable anti-
Luab and recognizes a common
antigen, Lu3, that is present
whenever Lua or Lub is present
Made only by individuals with
the recessive type of Lu(a–b–)
BLOOD BANK CHAP 8

LUTHERAN Phenotypes

Dominant Type Lu(a-b-) Recessive Type Lu(a-b-) Recessive X-Linked

expression of Lutheran was Inhibitor Type
thought to be suppressed by a
rare dominant regulator gene The result of having two rare An Lu(a–b–) phenotype in a
later called In(Lu) for silent alleles LuLu at the large Australian family did
“inhibitor of Lutheran” Lutheran locus not fit either the dominant
Mutations in the gene for truly lack all Lutheran or recessive inheritance
Erythroid Krüppel-like Factor antigens (i.e., they have the patterns
(EKLF), a transcription factor, null phenotype) and can make The pattern of inheritance
were shown to be associated with anti-Lu3 suggested an X-borne
the In(Lu) phenotype in 21 of 24 inhibitor to Lutheran
In(Lu) individuals studied
In addition to reduced
expression of Lutheran antigens,
dominant type Lu(a–b–) RBCs also
can have reduced expression of
CD44 and a weak expression of P1,
i, AnWj, MER2, and Inb blood
group antigens
BLOOD BANK CHAP 8 - SUMMARY
BLOOD BANK CHAP 8 - END

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