BB. MLT309. 2013-2014.Lec.6.Mr. Waggas

Other Blood Group Systems

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. MLT309. 2013-2014.Lec.6.Mr. Waggas

Major Blood Group Systems Lewis I P MNSs Kell Kidd Duffy BB. MLT309. 2013-2014.Lec.6.Mr. Waggas

Systems that Produce Cold-Reacting Antibodies

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. MLT309. 2013-2014.Lec.6.Mr. Waggas

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. MLT309. 2013-2014.Lec.6.Mr. Waggas

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. MLT309. 2013-2014.Lec.6.Mr. Waggas

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. MLT309. 2013-2014.Lec.6.Mr. Waggas

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. MLT309. 2013-2014.Lec.6.Mr. Waggas

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. MLT309. 2013-2014.Lec.6.Mr. Waggas

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. MLT309. 2013-2014.Lec.6.Mr. Waggas

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. MLT309. 2013-2014.Lec.6.Mr. Waggas

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. MLT309. 2013-2014.Lec.6.Mr. Waggas

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. MLT309. 2013-2014.Lec.6.Mr. Waggas

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. MLT309. 2013-2014.Lec.6.Mr. Waggas

P1 Antigen Strength of the antigen decreases upon storage Found in secretions like plasma and hydatid cyst fluid Cyst of a dog tapeworm BB. MLT309. 2013-2014.Lec.6.Mr. Waggas

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. MLT309. 2013-2014.Lec.6.Mr. Waggas

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. MLT309. 2013-2014.Lec.6.Mr. Waggas

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)

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. MLT309. 2013-2014.Lec.6.Mr. Waggas

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

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% BB. MLT309. 2013-2014.Lec.6.Mr. Waggas

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. MLT309. 2013-2014.Lec.6.Mr. Waggas

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. MLT309. 2013-2014.Lec.6.Mr. Waggas

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. MLT309. 2013-2014.Lec.6.Mr. Waggas

Systems that Produce Warm-Reacting Antibodies

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. MLT309. 2013-2014.Lec.6.Mr. Waggas

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. MLT309. 2013-2014.Lec.6.Mr. Waggas

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. MLT309. 2013-2014.Lec.6.Mr. Waggas

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. MLT309. 2013-2014.Lec.6.Mr. Waggas

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. MLT309. 2013-2014.Lec.6.Mr. Waggas

Kidd Antigens Well developed at birth Enhanced by enzymes Not very accessible on the RBC membrane BB. MLT309. 2013-2014.Lec.6.Mr. Waggas

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. MLT309. 2013-2014.Lec.6.Mr. Waggas

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. MLT309. 2013-2014.Lec.6.Mr. Waggas

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. MLT309. 2013-2014.Lec.6.Mr. Waggas

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. MLT309. 2013-2014.Lec.6.Mr. Waggas

Other Blood Group Antigens…

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. MLT309. 2013-2014.Lec.6.Mr. Waggas

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. MLT309. 2013-2014.Lec.6.Mr. Waggas

Cold Antibodies (IgM) LIiPMABHN Anti-Lea Anti-Leb Anti-I Anti-P1 Anti-M Anti-A, -B, -H Anti-N LIiPMABHN Naturally Occurring BB. MLT309. 2013-2014.Lec.6.Mr. Waggas

Warm antibodies (IgG) Rh Kell Duffy Kidd S,s U BB. MLT309. 2013-2014.Lec.6.Mr. Waggas

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. MLT309. 2013-2014.Lec.6.Mr. Waggas

Thanks BB. MLT309. 2013-2014.Lec.6.Mr. Waggas