other blood group systems

1. Other Blood Group Systems Renee Wilkins, PhD, MLS(ASCP)cm CLS 325/435 School of Health Related Professions University of Mississippi Medical Center

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

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-) May become hemolytic in vitro (in the tube) If pregnant women have Le antibodies detected, they need to first be neutralized so that HDN antibodies may be detectedMay become hemolytic in vitro (in the tube) If pregnant women have Le antibodies detected, they need to first be neutralized so that HDN antibodies may be detected

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 PCH- paroxysmal cold hemoglobinuriaPCH- paroxysmal cold hemoglobinuria

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

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

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

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%) Kpa = Penney Kpb = Rautenberg Jsa = Sutter Jsb = MatthewsKpa = Penney Kpb = Rautenberg Jsa = Sutter Jsb = Matthews

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

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

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

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

50. Remember enzyme activity:

51. Remembering Dosage: Kidds and Duffy the Monkey (Rh) eat lots of M&Ns