Unit 9 Other Blood Group Systems Part 2 Terry Kotrla, MS, MT(ASCP)BB Systems that Produce Cold-Reacting Antibodies Covered So Far I i Lewis P MNSs Blood System (ISBT 002) 4 important antigens (more exist): M N S s U (ALWAYS present when S & s are inherited) Antibodies M – antibodies USUALLY reactive at RT N - antibodies USUALLY reactive at RT S – antibodies are clinically significant s – antibodies are clinically significant U - antibodies are clinically significant MNSs Antibodies – General Information 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) Dosage Cell IS 37 IgG 1 M+N= (MM) 3+ 1+ 0 2 M+N+ (MN) 2+ 0 0 3 N+N+ (NN) 0 0 0 Cell 1 is homozygous for M, it has a “double” dose of the antigen and all antigens on the cell for this blood group will be M. Notice the 3+ reaction. Cell 2 is heterozygous, a single dose of each, only 50% of the antigens will be M and 50% will be N. Notice the 2+ reaction Because there are a decreased number of ANTIGENS you will expect DECREASED serologic reactivity. When varying strengths of reactions are noted within a single phase of reactivity THINK DOSAGE first and multiple antibodies second. Anti-M Frequently detected as a naturally occurring saline agglutinin at RT testing. Most examples occur WITHOUT red cell stimulus. Weak examples of the antibody can be enhanced by “acidifying” the serum, lowering the pH to 6.5. RARE examples have been found that are partly or wholly IgG which have caused HDFN or HTR MOST are clinically INSIGNIFICANT, no HDFN or HTR. Do NOT need to confirm donors are M negative, must be crossmatch compatible. Will NOT react with enzyme treated cells. Anti-N Rarely encountered. IgM Typically weakly reactive at RT Considered clinically insignificant although RARE examples of IgG have been observed. Do NOT need to confirm donors are M negative, must be crossmatch compatible. Will NOT react with enzyme treated cells. N Typing Reagent Lectin extracted from Vicia graminea has specificity for N antigen. Add to test RBCs as well as positive and negative controls. N antigen present = positive agglutination reaction. N antigen absent = negative agglutination reaction. Variant MN Antigen Mg VERY RARE Person with genotype Mg N will test as M=N+ leading to false conclusion that genotype is NN. Of primary importance in paternity testing. S, s and U Antigens S and s produced by pair of allelic antigens at locus closely linked to MN locus. White Black S+s=U+ 11% 3% S+s+U+ 44% 28% S=s+U+ 45% 69% S=s=U= 0% Less than 1% Frequency of MNSs antigens Phenotypes M+ Blacks (%) 74 Whites (%) 78 N+ 75 72 S+ 30.5 55 s+ 94 89 U+ 99 99.9 High-incidence antigen S, s and U Antibodies Clinically significant IgG Causes HDFN and HTR Will NOT react with enzyme treated cells, antigens are destroyed by enzyme treatment. Must confirm that donor units are negative for antigen(s). Donor units must be crossmatch compatible. U (Su) The U antigen is ALWAYS present when S and s are inherited Establish as U negative by proving they are S=s=. Can only give U-negative blood units found in <1% of Black population Suspect anti-U when a pregnant or previously transfused black individual reacts with ALL cells tested and has a negative autocontrol. Will NOT find U negative blood in any population except the black population. Two potential sources are siblings and rare donor blood. 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% Summary of MNSs Antibody Characteristics Antibody Anti-M IgG Class Clinically significant IgM (rare IgG) No Anti-N IgM No Anti-S IgG Yes Anti-s IgG Yes Anti-U IgG Yes Lutheran Blood Group System (ISBT 005) First example of anti-Lua was found in 1946. Two codominant alleles: Lua and Lub Antigens are poorly developed at birth. Lutheran Antigens Genotype Frequency Lu(a+b=) 0.15% Lu (a+b+) 7.5% Lu (a=b+) 92.35% Lu (a=b=) Very Rare Anti-Lua Uncommon, usually naturally occurring saline agglutinin. Not clinically significant Reacts at room temperature RARE Mild HDN Naturally occurring or RARELY immune stimulated. May agglutinate RBCs in-vitro in MF manner which is a characteristic helpful in identifying. Donors do NOT need to be antigen typed, must be crossmatch compatible. Anti-Lub Clinically significant IgG. Has caused MILD HDFN. Has been reported to cause diminished survival of transfused RBCs (HTR). Rare because Lub is high incidence antigen. Finding compatible blood difficult, 99% of population is positive. What are two potential sources of compatible blood? Donors must be antigen negative AND crossmatch compatible. Systems that Produce WarmReacting Antibodies Kell System (ISBT 006) K antigen first identified in 1946 as causative antibody in case of HDFN. 2 major alleles (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 Kell antibodies Produced as a result of immune stimulation. IgG (react well at AHG) Clinically significant Anti-K is most common because the K antigen is extremely immunogenic Caused numerous cases of HTRs both immediate and delayed. Cause of severe HDFN. Anti-k occurs much less frequently due to high frequency of antigen, <1 in 500 people are k negative. Donor units must be antigen negative, crossmatch compatible. Other Kell System Antigens Other sets of alleles also exist in the Kell system. Kp antigens Kpa (Penney, KEL3, 1957) low frequency antigen (only 2%) Kpb (Rautenberg, KEL4, 1958) high frequency antigen (99.9%) Js antigens Jsa (Sutter, KEL6, 1958), 20% in Blacks, 0.1% in Whites Jsb (Matthews, KEL7, 1963), is high frequency 80-100% K is a null phenotype. McLeod McLeod Syndrome Phenotype has weakened expression of Kell system antigens Associated with structural and functional abnormalities of RBCs and leukocytes. 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) Other Kell System Antibodies Similar serologic characteristics. Clinically significant, immune antibodies. Frequency of detection influenced by Immunogenicity Distribution of antigen in population. Antibodies are rare which suggests low immunogenicity. If antigen 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 Kidd Antigens Well developed at birth Enhanced by enzymes Not very accessible on the RBC membrane 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 Kidd antibodies Anti-Jk3 Found in some individuals who are Jk(a-b-) Far East and Pacific Islanders (RARE) 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 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 as antigens are destroyed/denatured. The Duffy and Malaria Connection Most African-Americans are Fy(a-b-) Certain malarial parasites (Plasmodium knowlesi and P. vivax) cannot invade Fya and Fyb negative cells Antigen acts as a receptor for invasion and 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 Other Blood Group Antigens… Bg Antigens Three (Bennett-Goodspeed) Bg antigens: Bga Bgb Bgc Related to human leukocyte antigens (HLA) on RBCs Antibodies are not clinically significant 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 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 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 Review Cold Antibodies IgM React at RT or colder NO HDFN or HTR Donor units do not need to be phenotyped for antigen. Donor units must be crossmatch compatible. Cold Antibodies (IgM) Anti-Lea Anti-Leb Anti-I Anti-P1 Anti-M Anti-A, -B, -H Anti-N LIiPMABHN Naturally Occurring Cold Reacting Antibodies Warm Antibodies IgG React at 37C and, most frequently, at AHG Cause of HDFN and HTR Donor units must be phenotyped for antigen and be antigen negative. Donor units must be crossmatch compatible. Warm antibodies (IgG) Rh antibodies Kidd Kell Duffy S,s Warm Reacting Antibodies Remember enzyme activity: Papain, bromelin, ficin, and trypsin Enhanced by enzymes Destroyed by enzymes Kidd Rh Lewis I P Fya and Fyb M, N S, s Remembering Dosage: Kidds and Duffy the Monkey (Rh) eat lots of M&Ns M&Ns M&Ns Jka, Jkb, Kidd Fya, Fyb, Duffy C, c, E, e (no D), Rh M, N, S, s MNSs adapted from Clinical Laboratory Science Review: A Bottom Line Approach (3rd Edition) References Renee Wilkins, PhD, MLS(ASCP)cm University of Mississippi Medical Center AABB Technical Manual, 16th edition, 2008 Basic and Applied Concepts of Immunohematology, 2nd edition, 2008
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