Minor Blood Group Systems Nada Mohamed Ahmed , MD, MT (ASCP)i

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

Objectives of Minor Blood Group Systems Lewis Kell Kidd Antibodies Duffy Antigens rare characteristic

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 Dosage effect amount of the product of the gene. Enzymes enhance activity they speed up reactions by providing an alternative reaction pathway of lower activation energy.

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

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.

Lewis Antibodies Usually occur naturally in those who are Le(a-b-) 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 detected

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

Kell antibodies Clinically significant 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 antibodies are rare (many individuals have these antigens and won’t develop an antibody)

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

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

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

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(infective stage of Malaria) 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

Cold Antibodies (IgM) Naturally Occurring Anti-Lea Anti-Leb Anti-A, -B, -H Naturally Occurring

Warm antibodies (IgG) Rh antibodies Kell Duffy Kidd

Remember enzyme activity: Enhanced by enzymes Destroyed by enzymes Kidd Rh Lewis Fya and Fyb Papain, bromelin, ficin, and trypsin

Remembering Dosage: Kidds and Duffy the Monkey (Rh) eat lots of doses. Jka, Jkb, Fya, Fyb, C, c, E, e (no D), Kidd Duffy Rh