Transcript Other Blood Group Systems

Other Blood Group
Systems
Renee Wilkins, PhD, MLS(ASCP)cm
CLS 325/435
School of Health Related Professions
University of Mississippi Medical Center
Facts
Over 200 blood antigens exist!
 Unfortunately, we only get to review the
most relevant antigens
 We will discuss each of these major
antigens, their antibodies, and the clinical
significance of each

Major Blood Group Systems
Lewis
I
P
 MNSs
 Kell
 Kidd
 Duffy

Basic terms to remember
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Clinical significance: antibodies that are
associated with decreased RBC survival
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Transfusion reactions
HDN
Not clinically significant: antibodies that do
not cause red cell destruction
Cold reacting antibodies: agglutination best
observed at or below room temp.
Warm reacting antibodies: agglutination best
observed at 37°C
Systems that Produce
Cold-Reacting Antibodies
Lewis Antigens
Soluble antigens produced by tissues and
found in body fluids (plasma)
 Adsorbed on the RBC

Lewis substance
adheres to RBC
becoming an antigen
RBC
Le
genes
Le substance
in plasma
Lewis inheritance
Lewis system depends on Hh, Se, and Le
genes
 le, h, and se do not produce products
 If the Le gene is inherited, Lea substance
is produced
 Le, H, and Se genes must ALL be inherited
to convert Lea to Leb. Examples:
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Le se H
Le Se H
le H se
le hh se
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Le(a+b-)
Le(a-b+)
Le(a-b-)
Le(a-b-)
Lewis Antibodies
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Usually occur naturally in those who are Le(a-b-)
Other phenotypes RARELY produce the antibody
IgM (may fix complement, becoming hemolytic)
Enzymes enhance activity
May be detected soon after pregnancy because
pregnant women may temporarily become Le(a-b-)
No clinical significance…Why?
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Le antibodies in a patient can be neutralized by the Lewis
antigens in the donor’s plasma (cancel each other out)
do not cause HDN because they do not cross placenta
(antigens not developed well in cord blood)
Le(a-b-)
I antigens
These antigens may be I or i
 They form on the precursor chain of RBC
 Newborns have i antigen
 Adults have I antigen
 i antigen (linear) converts to I (branched)
as the child matures (precursor chain is
more linear at birth) at about 18 months

I antibodies
Most people have autoanti-I (RT or 4°C)
 Alloanti-I is very rare
 Cold-reacting (RT or below) IgM antibody
 Clinically insignificant
 Can attach complement (no hemolysis unless it
reacts at 37°)
 Prewarming the tests can eliminate reactivity
 Enzymes can enhance detection

I antibodies
Anti-I often occurs as anti-IH
 This means it will react at different
strengths with reagent cells (depending on
the amount of H antigen on the RBC)
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O cells would have a strong reaction
A cells would have a weaker reaction
Anti-I antibodies
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Anti-I:
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Associated as a cause of Cold Agglutinin
Disease (similar to PCH)
May be secondary to Mycoplasma
pneumoniae infections
Anti-i:
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rare and is sometimes associated with
infectious mononucleosis
P Antigen
Similar to the ABO system
 The most common phenotypes are P1 and
P2
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P1 – consists of P1 and P antigens
P2 – consists of only P antigens
Like the A2 subgroup, P2 groups can
produce anti-P1
 75% of adults have P1
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P1 Antigen
Strength of the antigen decreases upon
storage
 Found in secretions like plasma and
hydatid cyst fluid
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Cyst of a dog tapeworm
P antibodies
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Anti-P1
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Naturally occurring IgM
Not clinically significant
Can be neutralized by hydatid cyst fluid to reveal more
clinically significant antibodies
Anti-P
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Produced in individuals with paroxysmal cold
hemoglobinuria (PCH)
PCH – IgG auto-anti-P attaches complement when cold
(fingers, toes). As the red cells circulate, they begin to
lyse (releasing Hgb)
This PCH antibody is also called the DonathLandsteiner antibody
MNSs Blood System
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4 important antigens (more exist):
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M
N
S
s
U (ALWAYS present when S & s are inherited)
M & N located on Glycophorin A
 S & s and U located on Glycophorin B
 Remember: Glycophorin is a protein that
carries many RBC antigens
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MNSs Antigens
M
Glycophorin A
N
M & N only differ in
their amino acid
sequence at positions
1 and 5
RBC
Glycophorin B
COOH end …..
U
S
s
….5, 4, 3, 2, 1 (NH2 end)
S & s only differ in
their amino acid
sequence at position
29
MNSs antigens
all show dosage
 M & N give a stronger reaction when
homozygous, (M+N-) or (M-N+)
 Weaker reactions occur when in the
heterozygous state (M+N+)
 Antigens are destroyed by enzymes
(i.e. ficin, papain)

U (Su) antigen
The U antigen is ALWAYS present when S
& s are inherited
 About 85% of S-s- individuals are Unegative (RARE)
 U-negative cells are only found in the
Black population
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Frequency of MNSs antigens
Phenotypes
M+
Blacks
(%)
74
Whites
(%)
78
N+
75
72
S+
30.5
55
s+
94
89
U+
99
99.9
High-incidence antigen
Thought…..
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Can a person have NO MNSs antigens?
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Yes, the Mk allele produces no M, N, S, or s
antigens
Frequency of 0.00064 or .064%
Anti-M and anti-N antibodies
Demonstrate dosage
 Anti-M and anti-N
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IgM (rarely IgG)
Clinically insignificant
If IgG, could be implicated in HDN (RARE)
Will not react with enzyme treated cells
Anti-S, Anti-s, and Anti-U
Clinically significant
 IgG
 Can cause RBC destruction and HDN
 Anti-U
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will react with S+ or s+ red cells
Usually occurs in S-s- cells
Can only give U-negative blood units found in
<1% of Black population
Contact rare donor registry
MNSs Antibody Characteristics
Antibody
Anti-M
IgG Class
Clinically
significant
IgM (rare IgG)
No
Anti-N
IgM
No
Anti-S
IgG
Yes
Anti-s
IgG
Yes
Anti-U
IgG
Yes
Systems that Produce WarmReacting Antibodies
Kell System
Similar to the Rh system
 2 major antigens (over 20 exist)
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K (Kell), <9% of population
k (cellano), >90% of population
The K and k genes are codominant alleles
on chromosome 7 that code for the
antigens
 Well developed at birth
 The K antigen is very immunogenic (2nd to
the D antigen) in stimulating antibody
production
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Other Kell antigens
Other sets of alleles also exist in the Kell
system:
 Analogous to the Rh system: C/c and E/e
 Kp antigens
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Kpa is a low frequency antigen (only 2%)
Kpb is a high frequency antigen (99.9%)
Js antigens
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Jsa (20% in Blacks, 0.1% in Whites)
Jsb is high frequency (80-100%)
Kell antigens
Kell antigens have disulfide-bonded
regions on the glycoproteins
 This makes them sensitive to sulfhydryl
reagents:
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2-mercaptoethanol (2-ME)
Dithiothreitol (DTT)
2-aminoethylisothiouronium bromide (AET)
Kellnull or K0
No expression of Kell antigens except a
related antigen called Kx
 As a result of transfusion, K0 individuals
can develop anti-Ku (Ku is on RBCs that
have Kell antigens)
 Rare Kell negative units should be given
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Kell antibodies
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IgG (react well at AHG)
Produced as a result of immune stimulation
(transfusion, pregnancy)
Clinically significant
Anti-K is most common because the K antigen
is extremely immunogenic
k, Kpb, and Jsb antibodies are rare (many
individuals have these antigens and won’t
develop an antibody)
The other antibodies are also rare since few
donors have the antigen
Kx antigen
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Not a part of the Kell system, but is
related
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Kx antigens are present in small amounts in
individuals with normal Kell antigens
Kx antigens are increased in those who are K0
McLeod Syndrome
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The XK1 gene (on the X chromosome) codes for
the Kx antigen
When the gene is not inherited, Kx is absent
(almost exclusive in White males)
Causes abnormal red cell morphologies and
decreased red cell survival:
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Acanthocytes – spur cells (defected cell membrane)
Reticulocytes – immature red cells
Associated with chronic granulomatous
disease
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WBCs engulf microorganisms, but cannot kill (normal
flora)
Kidd Blood Group
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2 antigens
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Jka and Jkb (codominant alleles)
Show dosage
Genotype Phenotype Whites (%) Blacks (%)
JkaJka
Jk(a+b-)
26.3
51.1
JkaJkb
Jk(a+b+
50.3
40.8
JkbJkb
Jk(a-b+)
23.4
8.1
JkJk
Jk(a-b-)
rare
rare
Kidd Antigens
Well developed at birth
 Enhanced by enzymes
 Not very acessible on the RBC membrane
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Kidd antibodies
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Anti-Jka and Anti-Jkb
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IgG
Clinically significant
Implicated in HTR and HDN
Common cause of delayed HTR
Usually appears with other antibodies when
detected
Kidd antibodies
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Anti-Jk3
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Found in some individuals who are Jk(a-b-)
Far East and Pacific Islanders (RARE)
Duffy Blood Group
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Predominant genes (codominant alleles):
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Fya and Fyb code for antigens that are well
developed at birth
Antigens are destroyed by enzymes
Show dosage
Phenotypes
Blacks
Whites
Fy(a+b-)
9
17
Fy(a+b+)
1
49
Fy(a-b+)
22
34
Fy(a-b-)
68
RARE
Duffy antibodies
IgG
 Do not bind complement
 Clinically significant
 Stimulated by transfusion or pregnancy
(but not a common cause of HDN)
 Do not react with enzyme treated RBCs
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The Duffy and Malaria Connection
Most African-Americans are Fy(a-b-)
 Interestingly, certain malarial parasites
(Plasmodium knowlesi and P. vivax) will
not invade Fya and Fyb negative cells
 It seems either Fya or Fyb are needed for
the merozoite to attach to the red cell
 The Fy(a-b-) phenotype is found
frequently in West and Central Africans,
supporting the theory of selective
evolution
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Other Blood Group
Antigens…
Lutheran Blood Group System
2 codominant alleles: Lua and Lub
 Weakly expressed on cord blood cells
 Most individuals (92%) have the Lub
antigen, Lu(a-b+)
 The Lu(a-b-) phenotype is RARE
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Lutheran antibodies
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Anti-Lua
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IgM and IgG
Not clinically significant
Reacts at room temperature
Mild HDN
Naturally occurring or immune stimulated
Anti-Lub
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Rare because Lub is high incidence antigen
IgG
Associated with transfusion reactions (rare HDN)
Bg Antigens
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Three (Bennett-Goodspeed) Bg antigens:
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Bga
Bgb
Bgc
Related to human leukocyte antigens
(HLA) on RBCs
 Antibodies are not clinically significant
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Sda Antigens
High incidence antigens found in tissues
and body fluids
 Antibodies are not clinically significant
 Antibodies characteristically cause mixed
field agglutination with reagent cells
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Xg Blood Group
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Only one exists (Xga)
Inheritance occurs only on the X chromosome
 89% Xga in women
 66% in males (carry only one X)
Men could be genotype Xga or Xg
Women could be XgaXga, XgaXg, or XgXg
Example: Xg(a+) male with Xg(a-) woman would only
pass Xg(a+) to daughters, but not sons
The antigen is not a strong immunogen (not attributed to
transfusion reactions); but antibodies may be of IgG class
HTLA Antigens
High Titer Low Avidity (HTLA)
 Occur with high frequency
 Antibodies are VERY weak and are not
clinically significant
 Do not cause HDN or HTR
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Review
Cold Antibodies (IgM)
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Anti-Lea
Anti-Leb
Anti-I
Anti-P1
Anti-M
Anti-A, -B, -H
Anti-N
LIiPMABHN
Naturally Occurring
Warm antibodies (IgG)
Rh antibodies
 Kell
 Duffy
 Kidd
 S,s
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Remember enzyme activity:
Papain, bromelin,
ficin, and trypsin
Enhanced by
enzymes
Destroyed
by enzymes
Kidd
Rh
Lewis
I
P
Fya and Fyb
M, N
S, s
Remembering Dosage:

Kidds and Duffy the Monkey (Rh) eat
lots of M&Ns
M&Ns
M&Ns
Jka, Jkb,
Kidd
Fya, Fyb,
Duffy
C, c, E, e (no D),
Rh
M, N, S, s
MNSs
adapted from Clinical Laboratory Science Review: A Bottom Line Approach (3rd Edition)