1. Other Blood Group
Systems
BUDANG

2. 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

3. Major Blood Group Systems
 Lewis
I
P
 MNSs
 Kell
 Kidd
 Duffy

4. Basic terms to remember
 Clinical significance: antibodies that are
associated with decreased RBC survival
 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

5. Systems that Produce
Cold-Reacting Antibodies

6. 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 substance
in plasma
Le
genes

7. 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:
 Le se H  Le(a+b-)
 Le Se H  Le(a-b+)
 le H se  Le(a-b-)
 le hh se  Le(a-b-)

8. 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…Why?
 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-)

9. 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

10. 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

11. 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 would have a weaker reaction

12. Anti-I antibodies
 Anti-I:
 Associated as a cause of Cold Agglutinin
Disease (similar to PCH)
 May be secondary to Mycoplasma
pneumoniae infections
 Anti-i:
 rare and is sometimes associated with
infectious mononucleosis

13. 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

14. P1 Antigen
 Strength of the antigen decreases upon
storage
 Found in secretions like plasma and
hydatid cyst fluid
 Cyst of a dog tapeworm

15. P antibodies
 Anti-P1
 Naturally occurring IgM
 Not clinically significant
 Can be neutralized by hydatid cyst fluid to reveal more
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 Hgb)
 This PCH antibody is also called the Donath-
Landsteiner antibody

16. MNSs Blood System
 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
 Remember: Glycophorin is a protein that
carries many RBC antigens

17. MNSs Antigens
M & N only differ in
M their amino acid
Glycophorin A N sequence at positions
1 and 5
RBC
S S & s only differ in
U
Glycophorin B s their amino acid
sequence at position
29
COOH end ….. ….5, 4, 3, 2, 1 (NH2 end)

18. 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)

19. U (Su) antigen
 The U antigen is ALWAYS present when S
& s are inherited
 About 85% of S-s- individuals are U-
negative (RARE)
 U-negative cells are only found in the
Black population

20. Frequency of MNSs antigens
Phenotypes Blacks Whites
(%) (%)
M+ 74 78
N+ 75 72
S+ 30.5 55
s+ 94 89
U+ 99 99.9
High-incidence antigen

21. Thought…..
 Can a person have NO MNSs antigens?
 Yes, the Mk allele produces no M, N, S, or s
antigens
 Frequency of 0.00064 or .064%

22. 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

23. 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

24. 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

25. Systems that Produce Warm-
Reacting Antibodies

26. Kell System
 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

27. 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%)

28. 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)

29. 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

30. 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

31. 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

32. 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:
 Acanthocytes – spur cells (defected cell membrane)
 Reticulocytes – immature red cells
 Associated with chronic granulomatous
disease
 WBCs engulf microorganisms, but cannot kill (normal
flora)

33. Kidd Blood Group
 2 antigens
 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

34. Kidd Antigens
 Well developed at birth
 Enhanced by enzymes
 Not very acessible on the RBC membrane

35. 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

36. Kidd antibodies
 Anti-Jk3
 Found in some individuals who are Jk(a-b-)
 Far East and Pacific Islanders (RARE)

37. 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

38. 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

39. 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

40. Other Blood Group
Antigens…

41. 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

42. 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)

43. Bg Antigens
 Three (Bennett-Goodspeed) Bg antigens:
 Bga
 Bgb
 Bgc
 Related to human leukocyte antigens
(HLA) on RBCs
 Antibodies are not clinically significant

44. 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

45. 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

46. 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

47. Review

48. Cold Antibodies (IgM)
 Anti-Lea
 Anti-Leb
 Anti-I
 Anti-P1
 Anti-M
 Anti-A, -B, -H
 Anti-N
LIiPMABHN
Naturally Occurring

49. Warm antibodies (IgG)
 Rh antibodies
 Kell
 Duffy
 Kidd
 S,s

50. Remember enzyme activity:
Papain, bromelin, Enhanced by Destroyed
ficin, and trypsin enzymes by enzymes
Kidd Fya and Fyb
Rh M, N
Lewis S, s
I
P

51. Remembering Dosage:
 Kidds and Duffy the Monkey (Rh) eat
lots of M&Ns
M&Ns
M&Ns
Jka, Jkb, Fya, Fyb, C, c, E, e (no D), M, N, S, s
MNSs
Kidd Duffy Rh