This document discusses several major blood group systems including Lewis, I, P, MNSs, Kell, Kidd, Duffy, Lutheran, Bg, Sda, and Xg. It provides information on the antigens and genes involved in each system, the clinical significance of associated antibodies, and inheritance patterns. Some key points covered include that Lewis, I, and P antigens produce cold-reacting antibodies while Kell, Kidd, and Duffy produce warm-reacting antibodies. The MNSs, Kell, and Kidd systems can produce clinically significant antibodies implicated in hemolytic transfusion reactions and hemolytic disease of the newborn.

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