1. BB. MLT Lec.6.Mr. Waggas

2. Other Blood Group Systems

3. Introduction For each blood group system you MUST know:
Antigen development, if important.
Antibody class usually involved.
Phase of reactivity in in-vitro tests.
Clinical significance.
Whether donor units must be antigen negative.
Any unique characteristics of the blood group antigens and/or antibodies.
BB. MLT Lec.6.Mr. Waggas

4. Major Blood Group Systems
Lewis I P
MNSs
Kell
Kidd
Duffy
BB. MLT Lec.6.Mr. Waggas

5. Systems that Produce Cold-Reacting Antibodies

6. Lewis System (ISBT 007)
Major antigens Lea and Leb , they are glycoproteins
Antigens ARE NOT intrinsic to RBCs but are absorbed from the plasma and inserted into RBC membrane.
Genetic control reside in single gene “Le”
Amorph le, if homozygous will not have Lewis antigens
Lea formed first, then modified to form Leb
Lewis phenotype of RBC can be changed by incubating with plasma containing Lea or Leb glycoplipid.
BB. MLT Lec.6.Mr. Waggas

7. Lewis System Lewis antigens in infants
Antigens absent or extremely weak at birth
Expression of Leb is gradual
Birth Le (a-b-)
2 months Le(a+b-)
12 to 18 months Le(a+b+)
2 to 3 years Le (a-b+)
Lewis antigens cannot be used for paternity testing on infants. Why?
BB. MLT Lec.6.Mr. Waggas

8. Lewis Antigens and Pregnancy
Antigen strength may decline dramatically during pregnancy.
Transiently Le (a-b-) may produce Lewis antibodies during pregnancy.
Antigens return after delivery and antibodies disappear.
BB. MLT Lec.6.Mr. Waggas

9. Interaction of Le, Se and H Genes
The le, h and se genes are amorphs and produce no detectable products.
lele will not have Lewis antigens, but if Se present will have A, B and H in secretions
Genotype se/se and have one Lewis gene will have Lea in their secretions but no A, B or H.
BB. MLT Lec.6.Mr. Waggas

10. Lewis Antibodies Almost always IgM
Naturally occurring, NOT clinically significant
Almost always IgM
React most often at RT
Agglutination relatively fragile, easily dispersed
May cause ABO discrepancy if reverse cells have Lewis antigen.
Occur almost exclusively in Le (a-b-) and production of anti-Lea AND –Leb not unusual
Anti-Lea frequently encountered, anti-Leb rarely encountered.
BB. MLT Lec.6.Mr. Waggas

11. Lewis Antibodies
Although most react at RT reactivity may be seen at 37C, but is weaker and may be weakly reactive at AHG
Can bind complement and cause IN-VITRO hemolysis, most often with enzyme treated cells
Antibodies NOT implicated in HDFN – TWO REASONS
Antibodies are IgM and
Antigens are poorly developed at birth
BB. MLT Lec.6.Mr. Waggas

12. I Blood Group (ISBT 027) Antigens are I or I Newborns have i antigen
Adults have I antigen
i antigen converts to I as the child matures at about 18 months
BB. MLT Lec.6.Mr. Waggas

13. I antibodies
Are IgM, naturally occurring auto-agglutinins with low thermal range.
They are not clinically significant unless they react above 30oC.
Can attach complement (no hemolysis unless it reacts at 37°)
Enzymes can enhance detection
BB. MLT Lec.6.Mr. Waggas

14. 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
Remember : strength of H sub. : O > A2 > A2B > B > A1 > A1B.
BB. MLT Lec.6.Mr. Waggas

15. Anti-I antibodies Anti-I: Anti-i:
Associated as a cause of Cold Agglutinin Disease
May be secondary to Mycoplasma pneumoniae infections
Anti-i:
rare and is sometimes associated with infectious mononucleosis
PCH- paroxysmal cold hemoglobinuria
BB. MLT Lec.6.Mr. Waggas

16. P Blood Group (ISBT 003) 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
BB. MLT Lec.6.Mr. Waggas

17. P1 Antigen Strength of the antigen decreases upon storage
Found in secretions like plasma and hydatid cyst fluid
Cyst of a dog tapeworm
BB. MLT Lec.6.Mr. Waggas

18. P antibodies Anti-P1 Anti-P Naturally occurring IgM
Not clinically significant
Can be neutralized by hydatid cyst fluid
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
BB. MLT Lec.6.Mr. Waggas

19. MNSs Blood System 4 important antigens (more exist):
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
BB. MLT Lec.6.Mr. Waggas

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

21. MNSs antigens Antigens are destroyed by enzymes (i.e. ficin, papain)
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
BB. MLT Lec.6.Mr. Waggas

22. 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

23. Thought….. Can a person have NO MNSs antigens?
Yes, the Mk allele produces no M, N, S, or s antigens
Frequency of or .064%
BB. MLT Lec.6.Mr. Waggas

24. Anti-M and anti-N antibodies
IgM (rarely IgG)
Clinically insignificant
If IgG, could be implicated in HDN (RARE)
Will not react with enzyme treated cells
BB. MLT Lec.6.Mr. Waggas

25. 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
BB. MLT Lec.6.Mr. Waggas

26. MNSs Antibody Characteristics
IgG Class
Clinically significant
Anti-M
IgM (rare IgG) No
Anti-N
IgM
Anti-S
IgG
Yes
Anti-s
Anti-U
BB. MLT Lec.6.Mr. Waggas

27. Systems that Produce Warm-Reacting Antibodies

28. 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
BB. MLT Lec.6.Mr. Waggas

29. Kell antigens
Kell antigens have disulfide-bonded regions on the glycoproteins
This makes them sensitive to sulfhydryl reagents:
2-mercaptoethanol (2-ME)
Dithiothreitol (DTT)
So Kell system Ags are easily inactivated by treating RBCs with these substances.
BB. MLT Lec.6.Mr. Waggas

30. 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
BB. MLT Lec.6.Mr. Waggas

31. 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
BB. MLT Lec.6.Mr. Waggas

32. Kidd Blood Group 2 antigens Jka and Jkb (codominant alleles) 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
BB. MLT Lec.6.Mr. Waggas

33. Kidd Antigens Well developed at birth Enhanced by enzymes
Not very accessible on the RBC membrane
BB. MLT Lec.6.Mr. Waggas

34. 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
BB. MLT Lec.6.Mr. Waggas

35. Duffy Blood Group Predominant genes (codominant alleles):
Fya and Fyb code for antigens that are well developed at birth
Antigens are destroyed by enzymes
Phenotypes
Blacks
Whites
Fy(a+b-) 9 17
Fy(a+b+) 1 49
Fy(a-b+) 22 34
Fy(a-b-) 68
RARE
BB. MLT Lec.6.Mr. Waggas

36. 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
BB. MLT Lec.6.Mr. Waggas

37. 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
BB. MLT Lec.6.Mr. Waggas

38. Other Blood Group Antigens…

39. 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
BB. MLT Lec.6.Mr. Waggas

40. Lutheran antibodies Anti-Lua Anti-Lub 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)
BB. MLT Lec.6.Mr. Waggas

41. Cold Antibodies (IgM) LIiPMABHN Anti-Lea Anti-Leb Anti-I Anti-P1
Anti-M
Anti-A, -B, -H
Anti-N
LIiPMABHN
Naturally Occurring
BB. MLT Lec.6.Mr. Waggas

42. Warm antibodies (IgG) Rh Kell Duffy Kidd S,s U
BB. MLT Lec.6.Mr. Waggas

43. 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
BB. MLT Lec.6.Mr. Waggas

44. Thanks
BB. MLT Lec.6.Mr. Waggas