other chapter 4 (1).pptx PowerPoint presentation

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1. Chapter Four MINOR Blood Group Systems

2. 4.1.Kell Blood Group system 4.2 .Duffy Blood Group system 4.3 .Lutheran blood group system 4.4 .Lewis Blood group system 4.5. I blood group system 4.6. P blood group system 4.7.MNSs blood group system 4.8. Kidd (JK) blood group system

3. Learning objectives At the end of this chapter, the student should be able to: Briefly explain the characteristics and biochemistry of other blood group antigen. Name the type of immunoglobulin class produced in other blood group system and their reactivity. Compare and contrast the characteristics of antibodies in other blood group system.

4. 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

5. M in or Blood Group Systems Lewis I P MNSs Kell Kidd Duffy

6. 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

7. Systems that Produce Cold-Reacting Antibodies

8. Lewis Antigens Soluble antigens produced by tissues and found in body fluids (plasma) Adsorbed on the RBC Le genes Le substance in plasma RBC Lewis substance adheres to RBC becoming an antigen

9. 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, Le a substance is produced Le , H , and Se genes must ALL be inherited to convert Le a to Le b . 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-)

10. 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-)

11. 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

12. 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

13. 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

14. 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

15. P Antigen Similar to the ABO system The most common phenotypes are P 1 and P 2 P 1 – consists of P 1 and P antigens P 2 – consists of only P antigens Like the A 2 subgroup, P 2 groups can produce anti-P 1 75% of adults have P 1

16. P 1 Antigen Strength of the antigen decreases upon storage Found in secretions like plasma and hydatid cyst fluid Cyst of a dog tapeworm

17. P antibodies Anti-P 1 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

18. 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

19. 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 (NH 2 end) COOH end …..

20. 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)

21. U (S u ) 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

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 M k allele produces no M, N, S, or s antigens Frequency of 0.00064 or .064%

24. 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

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

26. MNSs Antibody Characteristics Antibody IgG 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

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 (2 nd to the D antigen) in stimulating antibody production

29. 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 Kp a is a low frequency antigen (only 2%) Kp b is a high frequency antigen (99.9%) Js antigens Js a (20% in Blacks, 0.1% in Whites) Js b is high frequency (80-100%)

30. 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)

31. Kell null or K No expression of Kell antigens except a related antigen called Kx As a result of transfusion, K individuals can develop anti-Ku (Ku is on RBCs that have Kell antigens) Rare Kell negative units should be given

32. 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, Kp b , and Js b 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

33. 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 K

34. 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)

35. Kidd Blood Group 2 antigens Jk a and Jk b (codominant alleles) Show dosage Genotype Phenotype Whites (%) Blacks (%) Jk a Jk a Jk(a+b-) 26.3 51.1 Jk a Jk b Jk(a+b+ 50.3 40.8 Jk b Jk b Jk(a-b+) 23.4 8.1 JkJk Jk(a-b-) rare rare

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

37. Kidd antibodies Anti-Jk a and Anti-Jk b IgG Clinically significant Implicated in HTR and HDN Common cause of delayed HTR Usually appears with other antibodies when detected

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

39. Duffy Blood Group Predominant genes (codominant alleles): Fy a and Fy b 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

40. 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

41. The Duffy and Malaria Connection Most African-Americans are Fy(a-b-) Interestingly, certain malarial parasites ( Plasmodium knowlesi and P. vivax ) will not invade Fy a and Fy b negative cells It seems either Fy a or Fy b 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

42. Other Blood Group Antigens…

43. Lutheran Blood Group System 2 codominant alleles: Lu a and Lu b Weakly expressed on cord blood cells Most individuals (92%) have the Lu b antigen, Lu(a-b+) The Lu(a-b-) phenotype is RARE

44. Lutheran antibodies Anti-Lu a IgM and IgG Not clinically significant Reacts at room temperature Mild HDN Naturally occurring or immune stimulated Anti-Lu b Rare because Lu b is high incidence antigen IgG Associated with transfusion reactions (rare HDN)

45. Review

46. Cold Antibodies (IgM) Anti-Le a Anti-Le b Anti-I Anti-P1 Anti-M Anti-A, -B, -H Anti-N LI i PMA BH N Naturally Occurring

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

48. Remember enzyme activity: Enhanced by enzymes Destroyed by enzymes Kidd Rh Lewis I P Fy a and Fy b M, N S, s Papain, bromelin, ficin, and trypsin

49. Remembering Dosage: Kidds and Duffy the Monkey ( Rh ) eat lots of M&Ns Jk a , Jk b , Fy a , Fy b , C, c, E, e (no D), M, N, S, s M&Ns adapted from Clinical Laboratory Science Review: A Bottom Line Approach (3 rd Edition) M&Ns Kidd Duffy Rh MNSs