Other Blood Groups The Kell Blood Group System
Other Blood Groups
The Kell Blood Group System
Background information The Kell blood group system was discovered in 1946. l Number of Kell antigens: > 20 l These antigens are third most potent, after those of the ABO and Rh blood groups, at triggering an immune reaction. l
Molecular information The KEL gene is found on chromosome 7 l The KEL gene is highly polymorphic, with different alleles at this locus encoding the 25 antigens that define the Kell blood group. l 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. l
Kell Blood Group System l l 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: l K+k- (genotype KK) l K+k+ (genotype Kk) l 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.
Frequency of Kell phenotypes Phenotype Caucasians Blacks K-k+ 91 % 98 % K+k- 0. 2 % Rare K+k+ 8. 8 2
Kx Substance l l l 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
Mc. Leod Phenotype l l Absence of Kx proteins in RBCs membrane lead to Mc. Leod Phenotype This absence cause: § abnormal RBCs shape (acanthocytes) & reduced in-vivo survival.
Chronic Granulomatous Disease Absence of Kx proteins in WBCs cause CGD l Leukocytes are able to phagocytose but not to kill bacteria l Patients with CGD have recurrent bacterial infections l Patients who lack Kx on RBCs & WBCs have both Mcleod and CGD l
Kell Null (K 0) Phenotype Kx 1. K 0 is a silent Kell allele 2. When homozygous K 0 K 0 inherited no Kell system antigens are expressed. 3. Kx antigen expression is enhanced 4. Very rare
Kell Antibodies l l 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 Abs class Yes Ig. G , (rarely) Ig. M Thermal range HDNB 4 - 37 Yes Transfusion Reactions Extravascular Intravascular Yes Rare
Duffy Blood Group System l l l 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 l Fy(a-b-) Caucasians become sensitized following transfusion with Fy(a+) or Fy(b+) blood l This suggest that Fy(a-b-) phenotype arises from different genes in the two populations l
Duffy Antigens l l l Fya, Fyb antigens are Destroyed by enzymes Abs DO NOT agglutinate enzyme treated cells Moderately immunogenic.
Duffy Antigens Phenotype Caucasians % Blacks % Fy (a+b+) 49 2 Fy (a+b-) 18 14 Fy (a-b+) 33 19 Fy (a-b-) rare 65
Duffy Antibodies l l l Ig. G antibodies and can Duffy Abs activate complement Clinically Abs class a Anti- Fy is more Significant frequently encountered Yes Ig. G b Anti- Fy is more frequently found in Thermal range HDNB patients produced multiple 4 - 37 Yes alloantibodies Transfusion Reactions Extravascular Intravascular Yes
Duffy and Malaria l l 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 l l 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 Phenotype Caucasians (%) Jk (a+ b-) 29 Jk (a+ b+) 49 Jk (a- b+) 22 Jk (a- b-) Exceedingly rare
Kidd Antigens & Antibodies l l l Ags are well developed at birth Have tendency to drop to low or undetectable levels following formation. Abs are of Ig. G 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 l l l Found nearly on all RBCS Their products are transferase enzymes that attach repeating units of Gal and Glc. NAc to the ABO Precursor Substance. Big I gene codes for branching of the Precursor Substance.
Ii Antigens l l l 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
I Antibodies: Anti-I l l 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 Abs class Rare Ig. M Thermal range HDNB 4 - 10 No Transfusion Reactions Extravascular Intravascular No rare
Anti i Antibodies l l l 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 l l The antigens M and N are produced by codominant 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 l l MN Locus genes produce Glycophorin A (GPA) – M-GPA’s 1 st five aa’s = Serine-Ser-Thr. Glycine – N-GPA’s 1 st five aa’s = Leucine-Ser-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 Phenotype Genotype 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) l S glycophorin B has Methionine aa at position 29 l s glycophorin B has Threonine aa at position 29 l Glycophorin B (GPB) is a glycoprotein also known as Ss-sialoglyprotein l
Ss Genotypes & Phenotypes Phenotype Genotype S+s- Frequency % Caucasians Blacks SS 11 6 S+s+ Ss 44 24 S-s+ ss 45 68 S-s- Su su 0 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.
Anti-M Antibodies l Variability of reactivity (Dosage) § Strong reactions with RBCs homozygous for MM § Weak reactions with RBCs heterozygous MN Anti-M Abs Clinically Significant Abs class Seldom Ig. G & Ig. M Thermal range HDNB 4 – 22 Rare 22 -37 rare Transfusion Reactions Extravascular Intravascular Rare No
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 Abs class Ig. M No Thermal range HDNB 4 - 22 No Transfusion Reactions Extravascular Intravascular No No
Anti-S and Anti-s antibodies Anti-S Abs Clinically Significant Abs class Ig. G & Ig. M Sometimes Anti-s Abs Clinically Significant Abs class Ig. G Yes Thermal range HDNB 4 - 37 Yes Transfusion Reactions Extravascular Intravascular Yes No
P Blood Group System l l 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: P 1, Pk, P and lower case p (silent allele) All antigens are expressed on glycolipids on red cells
Phenotypes, Detectable Antigens & Frequencies Phenotype Detectable Antigens Frequencies P 1 , P 79% P 21% Pk 1 P, Pk Rare Pk 2 Pk Rare p N/A Rare • Pk is the precursor of P. • Rare individuals do not convert Pk into P. • Those will have Pk on RBCs. Whites %
Anti-P 1 Antibodies Naturally occcurring Abs found in the serum of P 2 Individuals Anti-P 1 Abs Clinically Significant Abs class Ig. M occasionally Thermal range HDNB 4 – 22 Yes Rare 22 -37 Transfusion Reactions Extravascular Intravascular No Rare
Allo Anti-P Antibodies Naturally occcurring Abs found in the serum of Pk and p Individuals Allo Anti-P Abs Clinically Significant Abs class Yes Rare Ig. G Thermal range HDNB 4 – 37 S Rare Ig. M Transfusion Reactions Extravascular Intravascular No Yes
Auto anti-P Antibodies l l It is an Ig. G 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 Abs class Ig. G Yes Biphasic HDNB Binds at 0 Rare Hemolysis 37 Transfusion Reactions Extravascular Intravascular Rare Yes
Anti Tja Antibodies l l Combination of anti-P, anti-P 1 & anti-Pk Found in serum of individuals who have no P, P 1 & Pk Ags on red cells
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