Other Blood Groups

The Kell Blood Group System

Background information The Kell blood group system was discovered in 1946. Number of Kell antigens: > 20 These antigens are the third most potent, after those of the ABO and Rh blood groups, at triggering an immune reaction.

Molecular information The KEL gene is found on chromosome 7 The KEL gene is highly polymorphic, with different alleles at this locus encoding the 25 antigens that define the Kell blood group. The Kell protein is a polypeptide chain of 732 amino acids in length that becomes glycosylated at five different sites. It makes a single pass through the RBC membrane.

Kell Blood Group System XK gene produces Kx substance, which is a precursor of of Kell Ags Kel genes convert Kx substance into the Kell Ags on RBCs K (Kell) & k (cellano) are produced by allelic genes, this results into 3 phenotypes: K+k- (genotype KK) K+k+ (genotype Kk) K-k+ (genotype kk) Other allelic genes include: Kpa/Kpb, Jsa/Jsb

XK Gene (Chromosome X) KEL Gene RBC Kx Kell system glycoprotein: Kell Ag’s reside here. KEL Gene RBC

Frequency of Kell phenotypes Caucasians Blacks K-k+ 91 % 98 % K+k- 0.2 % Rare K+k+ 8.8 2

Kx Substance Kx substance is present on RBCs & WBCs Kell genes convert Kx substance into the Kell Ags on RBCs Kell genes do not convert Kx on WBCs

McLeod Phenotype Absence of Kx proteins in RBCs membrane lead to McLeod Phenotype This absence cause: abnormal RBCs shape (acanthocytes) & reduced in-vivo survival.

Chronic Granulomatous Disease Absence of Kx proteins in WBCs cause CGD Leukocytes are able to phagocytose but not to kill bacteria Patients with CGD have recurrent bacterial infections Patients who lack Kx on RBCs & WBCs have both Mcleod and CGD

Kell Null (K0) Phenotype 1. K0 is a silent Kell allele 2. When homozygous K0K0 inherited no Kell system antigens are expressed. 3. Kx antigen expression is enhanced 4. Very rare Kx

Kell Antibodies K- individuals produce anti-K when exposed to K+ cells Frequency of K is low (9%), easy to find compatible blood for the patient with anti-k. On the other hand frequency of k antigen is 99.9% Difficult to find blood

Antibodies produced against Kell antigens Kell Abs Clinically Significant Yes Abs class IgG , (rarely) IgM Thermal range 4 - 37 HDNB Transfusion Reactions Extravascular Intravascular Rare

Duffy Blood Group System The Duffy blood group was discovered in 1950. The Duffy glycoprotein is encoded by the FY gene, found on chromosome 1 , of which there are two main alleles, FYA and FYB. They are codominant. The Duffy gene codes for a glycoprotein also found in other tissues: brain, kidney, spleen, heart and lung. The Duffy glycoprotein is a transmembrane protein Five alleles at Duffy locus, the most important: Fya, Fyb & Fy (Silent Allele) Fya is more immunogenic than Fyb

Different genes Fy(a-b-) blacks do not produce anti-Fya or anti-Fyb following transfusion with Fy(a+) or Fy(b+) blood Fy(a-b-) Caucasians become sensitized following transfusion with Fy(a+) or Fy(b+) blood This suggest that Fy(a-b-) phenotype arises from different genes in the two populations

Duffy Antigens Fya, Fyb antigens are Destroyed by enzymes Abs DO NOT agglutinate enzyme treated cells Moderately immunogenic.

Duffy Antigens 65 49 18 Phenotype Caucasians % Blacks % Fy (a+b+) 2 14 Fy (a-b+) 33 19 Fy (a-b-) rare 65

Clinically Significant Transfusion Reactions Duffy Antibodies IgG antibodies and can activate complement Anti- Fya is more frequently encountered Anti- Fyb is more frequently found in patients produced multiple alloantibodies Duffy Abs Clinically Significant Yes Abs class IgG Thermal range 4 - 37 HDNB Transfusion Reactions Extravascular Intravascular

Duffy and Malaria Black people with the Duffy phenotype of Fy(a–b–) appear to have resistance to Plasmodium vivax & Plasmodium knowlesi causative agents of Malaria. Duffy antigens appear to be a receptor for the P. vivax organism and when the antigen is not present on the red blood cell membrane P. vivax is unable to access the red blood cell Some area’s of West Africa are 100% Fy(a–b–). Plasmodium falciparum binds to RBCs at integral glycophorin A & B

Kidd Blood Group System The Kidd blood group was discovered in 1950. The Kidd gene is located on chromosome 18 Three alleles: Jka, Jkb, Jk Codominant Inheritance Jk is a silent allele (amorph) The Kidd protein is an integral protein of the RBC membrane.

Kidd Phenotype Frequencies Caucasians (%) Jk (a+ b-) 29 Jk (a+ b+) 49 Jk (a- b+) 22 Jk (a- b-) Exceedingly rare

Kidd Antigens & Antibodies Ags are well developed at birth Have tendency to drop to low or undetectable levels following formation. Abs are of IgG type & can activate complement (Anti-Jka, Anti-Jkb ) Produced following transfusion or pregnancy Can cause HDNB They are also a very common cause of delayed HTRs

Ii Blood Group Found nearly on all RBCS Their products are transferase enzymes that attach repeating units of Gal and GlcNAc to the ABO Precursor Substance. Big I gene codes for branching of the Precursor Substance.

Ii Antigens Little i antigen is LINEAR Found on cord cells, predominantly Big I antigen is BRANCHED Gradually convert from i to I during the first 18 months of life. Not all i converted to I, some i still present on adult cells, normally. Rare adult individuals termed iadult do not express i Ag on their red cells The I and i antigen sites are considered uncompleted ABH active chains. When ABH are removed from RBCs more I Ags are expressed I structure located beneath the ABH Ags

Clinically Significant Transfusion Reactions I Antibodies: Anti-I Anti-I is naturally occurring often due to a Mycoplasma pneumoniae infection Anti-I reacts with all adult cells (including patient’s own, all reagent cells, all donor cells) Anti-I does not react with cord cells Auto-anti-I is a common “cold agglutinin” Anti-I Abs Clinically Significant Rare Abs class IgM Thermal range 4 - 10 HDNB No Transfusion Reactions Extravascular Intravascular rare

Antii Antibodies Antii is rarely found in healthy individuals Reacts preferably with cord cells anti-i can be found secondary to Infectious Mononucleosis. Transient: Only present with active disease

MNSs Blood Group System The antigens M and N are produced by co-dominant alleles closely linked to the S and s genes, which are also co-dominant.  Chromosome 4 contains these linked genes Genes produce two distinct glycophorins or sialyglycoproteins (SGP) on the RBC membrane.

MN Genetics MN Locus genes produce Glycophorin A (GPA) M-GPA’s 1st five aa’s = Serine-Ser-Thr-Thr-Glycine N-GPA’s 1st five aa’s = Leucine-Ser-Thr-Thr-Glutamic acid Amino acids (aa) 2, 3 & 4 are the same for both Glycophorin A (GPA) is a glycoprotein also known as MN-sialoglycoprotein

MN Genotypes & Phenotypes Frequency % M+N- MM 30 M+N+ MN 50 M-N+ NN 20

Ss Genetics Ss genes code for the production of Glycophorin B(GPB) S glycophorin B has Methionine aa at position 29 s glycophorin B has Threonine aa at position 29 Glycophorin B (GPB) is a glycoprotein also known as Ss-sialoglyprotein

Ss Genotypes & Phenotypes Frequency % Caucasians Blacks S+s- SS 11 6 S+s+ Ss 44 24 S-s+ ss 45 68 S-s- Susu 2 U antigen is a high incident antigen NOT seen in individuals who lack both S and s antigens.  Individuals who lack this antigen (<1%) have a high likelihood of forming anti-U as well as anti-S and anti-s. 

Clinically Significant Transfusion Reactions Anti-M Antibodies Anti-M Abs Clinically Significant Seldom Abs class IgG & IgM Thermal range 4 – 22 Rare 22-37 HDNB rare Transfusion Reactions Extravascular Intravascular Rare No Variability of reactivity (Dosage) Strong reactions with RBCs homozygous for MM Weak reactions with RBCs heterozygous MN

Clinically Significant Transfusion Reactions Anti-N antibodies Naturally occurring cold agglutinin Can form in patients with renal Failure During dialysis with formaldehyde sterilized equipment Formaldehyde may alter the N Ag structure making it appear foreign Anti-N Abs Clinically Significant No Abs class IgM Thermal range 4 - 22 HDNB Transfusion Reactions Extravascular Intravascular

Anti-S and Anti-s antibodies Anti-S Abs Clinically Significant Sometimes Abs class IgG & IgM Thermal range 4 - 37 HDNB Yes Transfusion Reactions Extravascular Intravascular No Anti-s Abs Clinically Significant Yes Abs class IgG Thermal range 4 - 37 HDNB Transfusion Reactions Extravascular Intravascular No

P Blood Group System Genetics: These genes code for enzymes that sequentially add sugars to precursor substance. This system is related to the ABO, Le and Ii systems. Genes: P1, Pk, P and lower case p (silent allele) All antigens are expressed on glycolipids on red cells

Phenotypes, Detectable Antigens & Frequencies Whites % P1 P1, P 79% P2 P 21% Pk1 P, Pk Rare Pk2 Pk p N/A Pk is the precursor of P. Rare individuals do not convert Pk into P. Those will have Pk on RBCs.

Clinically Significant Transfusion Reactions Anti-P1 Antibodies Anti-P1 Abs Clinically Significant occasionally Abs class IgM Thermal range 4 – 22 Rare 22-37 HDNB Yes Transfusion Reactions Extravascular Intravascular No Rare Naturally occcurring Abs found in the serum of P2 Individuals

Clinically Significant Transfusion Reactions Allo Anti-P Antibodies Naturally occcurring Abs found in the serum of Pk and p Individuals Allo Anti-P Abs Clinically Significant Yes Abs class IgM Rare IgG Thermal range 4 – 37S HDNB Rare Transfusion Reactions Extravascular Intravascular No

Clinically Significant Transfusion Reactions Auto anti-P Antibodies It is an IgG biphasic Ab associated with Paroxysmal Cold Hemoglobinuria (PCH) Binds complement at cold temperatures and activates that complement in warm temperatures lysing the red blood cells. Auto Anti-P Abs Clinically Significant Yes Abs class IgG Biphasic Binds at 0 Hemolysis 37 HDNB Rare Transfusion Reactions Extravascular Intravascular

Anti Tja Antibodies Combination of anti-P, anti-P1 & anti-Pk Found in serum of individuals who have no P, P1 & Pk Ags on red cells