2. Rare Blood Groups
Over 300 RBC antigens exist! and nearly 35
blood groups.
Blood group Ags are either CH(sugar) attached to
glycoproteins/ glycolipids or AA on a protein.
Against these Ags,Antibodies are formed and
some of Abs are significant in Transfusion
Medicine as a cause of
HTR.
HDN.
Auto-immune disease.
Others Non significant.
4. Antibodies classification
A.on the basis of Etiopathology.
1. Naturally occuring Abs.These appear
according to Landsteiner Law,ie A person
missing an Ag,will develop Ab against that
Ag.These are iso-antibodies,IgM.
2.Immune Antibodies.IgG
Alloimune/Isoimmune.(Non Self Ag)
3.Auto-immune Abs(Self Ag).IgG,IgM
5. B.Thermal Classification
1.Cold Abs. IgM or IgG.
Optimum Tempt for agglutination
4c (Range 0—37c)
IgM. Pentamer,cannot cross placenta but
strong complement activation.Activity↑by
enzymes
IgG. Monomer, can cross placenta(HDN) but
weak compliment fixator.
2. Warm Abs. IgG or IgA.Optimum Tempt
for agglutination 37c
10. Lewis Antigens(6) Leᵃ, Leᵇ
Soluble antigens(a,b) produced by tissues and
found in body fluids (plasma)
Adsorbed on the RBC
Le
genes-
19
Le substance
in plasma
RBC
Lewis substance
adheres to RBC
becoming an antigen
11. Lewis inheritance Le/Le , Le/le , le/le
Lewis system depends on ABH&Se,along
with Le genes(H,Se,Le on chrome19)
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 precursor to Leb. Examples:
Le se H Le(a+b-)
le Se H Le(a-b-)
le H se Le(a-b-)
le hh se Le(a-b-)
Le Se H → Le(a+b+)
12. Le—H(ABH)----Se
4 Precursor substances in body(1,2,3,4)
Precursor 1 and 3 in plasma & secretios.
Precursor 2 & 4 present on RBCs & cells.
Se enzyme,FUT2 acts in plasma &
secretions and H enzymes,FUT1 on cells.
Precursor 1 + Le,FUT3(Fucosyl Transferase)→Leᵃ
Precursor 1 + Se,FUT2→ Precursor Type 1H+Le→Leᵇ
Type 1H + A Gene Transferase→1A +Le,FUT3→ALeᵇ
1H+B Gene Transferase→1B +Le,FUT3→BLeᵇ
13. Lewis Genes and Product
Gene Genotype(Homo/
Heterozygoud)
Gene Product
1 H
h
H/H---H/h
h/h
H.Substance
No H. substance
2 Le
le
Le/Le--- Le/le
Le/le
a.Substance Leᵃ
No a. substance
3 Se
se
Se/Se--- Se/se
se/se
Substance 1H
No b.substance
14. Lewis blood grouping
Gene Product blood group Antibody
1 a Le(a+b-) b(anti-Leᵇ) Rare
2 b Le(a-b+) a(anti-Leᵃ) Rare
3 a+b Le(a+b+) No Ab
4 No a. No b. Le(a-b-) IgM(anti-Leᵃ,anti-Leᵇ
blood group based on
Ag
Abs follow
Landsteiner Law
15. Lewis Antibodies
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..
Le antibodies in a patient can be neutralized by the Lewis
antigens in the donor’s plasma (cancel each other ,No
HTR)
1.do not cause HDN because they do not cross placenta
2.antigens not developed well in cord blood
Le(a-b-)
16. 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
17. I antibodies Auto/Allo--Cold
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,but no hemolysis unless
it reacts at 37°so clinally insignificant
Prewarming the tests can eliminate reactivity
Enzymes can enhance detection
18. 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)
O cells would have a strong reaction
A cells/B cells would have a weaker reaction
19. Anti-I antibodies
Anti-I:
Primary/idiopathic. Associated as a cause of
Cold Agglutinin Disease (similar to PCH)
May be secondary to Mycoplasma
pneumoniae infections and Toxoplasmosis.
Anti-i:
rare and is sometimes associated with
infectious mononucleosis
20. P Antigen
Similar to the ABO system
The most common phenotypes are P1 and
P2
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 Ag
21. P1 Antigen
Strength of the antigen decreases upon
storage
Found in secretions like plasma and
hydatid cyst fluid
(Cyst of a dog tapeworm)
22. P antibodies
Anti-P1
Naturally occurring IgM
Not clinically significant
Can be neutralized by hydatid cyst fluid to reveal
more/other clinically significant antibodies
Anti-P
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 Hb)
This PCH antibody is also called the Donath-
Landsteiner antibody,Dual Ab(Ab/complement
interaction starts at cold and completed at warm)
23. MNSs Blood System(MN+Ss)
4 important antigens (more exist):
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
Glycophorin is a protein that carries
many RBC antigens
24. MNSs Antigens
RBC
Glycophorin A
Glycophorin B
M
N
S
s
U
M & N only differ in
their amino acid
sequence at positions
1 and 5
S & s only differ in
their amino acid
sequence at position
29
….5, 4, 3, 2, 1 (NH2 end)
COOH end …..
25. MNSs antigens
all show dosage(level depends on Gene)
M & N give a stronger reaction when
homozygous, (M/M M+N-)or(N/N M-N+)
Weaker reactions occur when in the
heterozygous state (M+N+)
Antigens are destroyed by enzymes
(i.e. ficin, papain)
26. U (Su) antigen
The U antigen is ALWAYS present when S
& s are inherited-Co inheritance
About 85% of S-s- individuals are U-
negative (RARE)
U-negative cells are only found in the
Black population
28. Thought…..
Can a person have NO MNSs antigens?
Yes, the Mk allele produces no M, N, S, or s
antigens
Frequency of 0.00064 to.064%(Rare)
29. Anti-M and anti-N antibodies
Demonstrate dosage
Anti-M and anti-N
IgM (rarely IgG)
Clinically insignificant
If IgG, could be implicated in HDN (RARE)
Will not react with enzyme treated cells
30. Anti-S, Anti-s, and Anti-U
Clinically significant
IgG
Can cause RBC destruction and HDN
Anti-U
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
31. MNSs Antibody Characteristics
Antibody Ig Class Clinically
significant
Anti-M IgM (rare IgG) No
Anti-N IgM No
Anti-S IgG Yes
Anti-s IgG Yes
Anti-U IgG Yes
33. Kell System KCE/kce
Similar to the Rh system
2 major antigens (over 20 exist)
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
34. 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
Kpa is a low frequency antigen (only 2%)
Kpb is a high frequency antigen (99.9%)
Js antigens
Jsa (20% in Blacks, 0.1% in Whites)
Jsb is high frequency (80-100%)
35. Kell antigens
Kell antigens have disulfide-bonded
regions on the glycoproteins
This makes them sensitive to sulfhydryl
reagents:
2-mercaptoethanol (2-ME)
Dithiothreitol (DTT)
2-aminoethylisothiouronium bromide (AET)
36. 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
37. Kell antibodies
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
38. Kx antigen
Not a part of the Kell system, but is
related
Kx antigens are present in small amounts in
individuals with normal Kell antigens
Kx antigens are increased in those who are K0
39. McLeod Syndrome
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:(Hemolysis)
Acanthocytes – spur cells (defected cell membrane)
Reticulocytes – immature red cells
Associated with chronic granulomatous
disease
WBCs engulf microorganisms, but cannot kill (normal
flora infection)
41. Kidd Antigens
Well developed at birth
Enhanced by enzymes
Not very acessible on the RBC membrane
42. Kidd antibodies
Anti-Jka and Anti-Jkb
IgG
Clinically significant
Implicated in HTR and HDN
Common cause of delayed HTR
Usually appears with other antibodies when
detected
44. Duffy Blood Group
Predominant genes (codominant alleles):
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
45. 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
46. 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
48. 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
49. Lutheran antibodies
Anti-Lua
IgM and IgG
Not clinically significant
Reacts at room temperature
Mild HDN
Naturally occurring or immune stimulated
Anti-Lub
Rare because Lub is high incidence antigen
IgG
Associated with transfusion reactions (rare HDN)
50. Bg Antigens
Three (Bennett-Goodspeed) Bg antigens:
Bga
Bgb
Bgc
Related to human leukocyte antigens
(HLA) on RBCs
Antibodies are not clinically significant
51. 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
52. Xg Blood Group
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
53. 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
55. Remember enzyme activity:
Enhanced by
enzymes
Destroyed
by enzymes
Kidd
Rh
Lewis
I
P
Fya and Fyb
M, N
S, s
Papain, bromelin,
ficin, and trypsin
56. Remembering Dosage:
Kidds and Duffy the Monkey (Rh) eat
lots of M&Ns
Jka, Jkb, Fya, Fyb, C, c, E, e (no D), M, N, S, s
M&Ns
M&Ns
Kidd Duffy Rh
MNSs
