3Background information The Kell blood group system was discovered in 1946.Number of Kell antigens: > 20These antigens are the third most potent, after those of the ABO and Rh blood groups, at triggering an immune reaction.
4Molecular information The KEL gene is found on chromosome 7The 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.
5Kell Blood Group System XK gene produces Kx substance, which is a precursor of of Kell AgsKel genes convert Kx substance into the Kell Ags on RBCsK (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
6XK Gene (Chromosome X) KEL Gene RBC Kx Kell system glycoprotein: Kell Ag’s reside here.KEL GeneRBC
7Frequency of Kell phenotypes CaucasiansBlacksK-k+91 %98 %K+k-0.2 %RareK+k+8.82
8Kx Substance Kx substance is present on RBCs & WBCs Kell genes convert Kx substance into the Kell Ags on RBCsKell genes do not convert Kx on WBCs
9McLeod PhenotypeAbsence of Kx proteins in RBCs membrane lead to McLeod PhenotypeThis absence cause:abnormal RBCs shape (acanthocytes) & reduced in-vivo survival.
10Chronic Granulomatous Disease Absence of Kx proteins in WBCs cause CGDLeukocytes are able to phagocytose but not to kill bacteriaPatients with CGD have recurrent bacterial infectionsPatients who lack Kx on RBCs & WBCs have both Mcleod and CGD
11Kell Null (K0) Phenotype 1. K0 is a silent Kell allele2. When homozygous K0K0 inherited no Kell system antigens are expressed.3. Kx antigen expression is enhanced4. Very rareKx
12Kell 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
13Antibodies produced against Kell antigens Kell AbsClinically SignificantYesAbs classIgG , (rarely) IgMThermal range4 - 37HDNBTransfusion ReactionsExtravascularIntravascularRare
14Duffy 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 proteinFive alleles at Duffy locus, the most important: Fya, Fyb & Fy (Silent Allele)Fya is more immunogenic than Fyb
15Different genesFy(a-b-) blacks do not produce anti-Fya or anti-Fyb following transfusion with Fy(a+) or Fy(b+) bloodFy(a-b-) Caucasians become sensitized following transfusion with Fy(a+) or Fy(b+) bloodThis suggest that Fy(a-b-) phenotype arises from different genes in the two populations
16Duffy Antigens Fya, Fyb antigens are Destroyed by enzymes Abs DO NOT agglutinate enzyme treated cellsModerately immunogenic.
18Clinically Significant Transfusion Reactions Duffy AntibodiesIgG antibodies and can activate complementAnti- Fya is more frequently encounteredAnti- Fyb is more frequently found in patients produced multiple alloantibodiesDuffy AbsClinically SignificantYesAbs classIgGThermal range4 - 37HDNBTransfusion ReactionsExtravascularIntravascular
19Duffy and MalariaBlack 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 cellSome area’s of West Africa are 100% Fy(a–b–).Plasmodium falciparum binds to RBCs at integral glycophorin A & B
20Kidd Blood Group System The Kidd blood group was discovered in 1950.The Kidd gene is located on chromosome 18Three alleles: Jka, Jkb, JkCodominant InheritanceJk is a silent allele (amorph)The Kidd protein is an integral protein of the RBC membrane.
22Kidd Antigens & Antibodies Ags are well developed at birthHave 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 pregnancyCan cause HDNBThey are also a very common cause of delayed HTRs
23Ii 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.
24Ii Antigens Little i antigen is LINEAR Found on cord cells, predominantlyBig I antigen is BRANCHEDGradually 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 cellsThe I and i antigen sites are considered uncompleted ABH active chains.When ABH are removed from RBCs more I Ags are expressedI structure located beneath the ABH Ags
25Clinically Significant Transfusion Reactions I Antibodies: Anti-IAnti-I is naturally occurring often due to a Mycoplasma pneumoniae infectionAnti-I reacts with all adult cells (including patient’s own, all reagent cells, all donor cells)Anti-I does not react with cord cellsAuto-anti-I is a common “cold agglutinin”Anti-I AbsClinically SignificantRareAbs classIgMThermal range4 - 10HDNBNoTransfusion ReactionsExtravascularIntravascularrare
26Antii Antibodies Antii is rarely found in healthy individuals Reacts preferably with cord cellsanti-i can be found secondary to Infectious Mononucleosis.Transient: Only present with active disease
27MNSs Blood Group System The antigens M and N are produced by co-dominant allelesclosely linked to the S and s genes, which are also co-dominant. Chromosome 4 contains these linked genesGenes produce two distinct glycophorins or sialyglycoproteins (SGP) on the RBC membrane.
28MN Genetics MN Locus genes produce Glycophorin A (GPA) M-GPA’s 1st five aa’s = Serine-Ser-Thr-Thr-GlycineN-GPA’s 1st five aa’s = Leucine-Ser-Thr-Thr-Glutamic acidAmino acids (aa) 2, 3 & 4 are the same for bothGlycophorin A (GPA) is a glycoprotein also known as MN-sialoglycoprotein
29MN Genotypes & Phenotypes Frequency %M+N-MM30M+N+MN50M-N+NN20
30Ss Genetics Ss genes code for the production of Glycophorin B(GPB) S glycophorin B has Methionine aa at position 29s glycophorin B has Threonine aa at position 29Glycophorin B (GPB) is a glycoprotein also known as Ss-sialoglyprotein
31Ss Genotypes & Phenotypes Frequency %CaucasiansBlacksS+s-SS116S+s+Ss4424S-s+ss4568S-s-Susu2U 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.
32Clinically Significant Transfusion Reactions Anti-M AntibodiesAnti-M AbsClinically SignificantSeldomAbs classIgG & IgMThermal range4 – 22Rare 22-37HDNBrareTransfusion ReactionsExtravascularIntravascularRareNoVariability of reactivity (Dosage)Strong reactions with RBCs homozygous for MMWeak reactions with RBCs heterozygous MN
33Clinically Significant Transfusion Reactions Anti-N antibodiesNaturally occurring cold agglutininCan form in patients with renal FailureDuring dialysis with formaldehyde sterilized equipmentFormaldehyde may alter the N Ag structure making it appear foreignAnti-N AbsClinically SignificantNoAbs classIgMThermal range4 - 22HDNBTransfusion ReactionsExtravascularIntravascular
35P Blood Group SystemGenetics: 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
36Phenotypes, Detectable Antigens & Frequencies Whites %P1P1, P79%P2P21%Pk1P, PkRarePk2PkpN/APk is the precursor of P.Rare individuals do not convert Pk into P.Those will have Pk on RBCs.
37Clinically Significant Transfusion Reactions Anti-P1 AntibodiesAnti-P1 AbsClinically SignificantoccasionallyAbs classIgMThermal range4 – 22Rare 22-37HDNBYesTransfusion ReactionsExtravascularIntravascularNoRareNaturally occcurring Abs found in the serum of P2 Individuals
38Clinically Significant Transfusion Reactions Allo Anti-P AntibodiesNaturally occcurring Abs found in the serum of Pk and p IndividualsAllo Anti-P AbsClinically SignificantYesAbs classIgMRare IgGThermal range4 – 37SHDNBRareTransfusion ReactionsExtravascularIntravascularNo
39Clinically Significant Transfusion Reactions Auto anti-P AntibodiesIt 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 AbsClinically SignificantYesAbs classIgGBiphasicBinds at 0Hemolysis 37HDNBRareTransfusion ReactionsExtravascularIntravascular
40Anti 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