* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Download Other Blood Groups
Survey
Document related concepts
Point mutation wikipedia , lookup
Site-specific recombinase technology wikipedia , lookup
Minimal genome wikipedia , lookup
Genomic imprinting wikipedia , lookup
Designer baby wikipedia , lookup
Polycomb Group Proteins and Cancer wikipedia , lookup
X-inactivation wikipedia , lookup
Biology and consumer behaviour wikipedia , lookup
Artificial gene synthesis wikipedia , lookup
Epigenetics of human development wikipedia , lookup
Genome (book) wikipedia , lookup
Dominance (genetics) wikipedia , lookup
Human leukocyte antigen wikipedia , lookup
Transcript
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. Frequency of Kell phenotypes Phenotype 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 Kx 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 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 Abs class Yes IgG , (rarely) IgM Thermal range HDNB 4 - 37 Yes Transfusion Reactions Extravascular Intravascular Yes 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 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 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 Abs class Yes IgG Thermal range HDNB 4 - 37 Yes Transfusion Reactions Extravascular Intravascular Yes Yes 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 Phenotype 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 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 Abs class Rare IgM Thermal range HDNB 4 - 10 No Transfusion Reactions Extravascular Intravascular No rare Antii Antibodies Antii 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 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 MN Locus genes produce Glycophorin A (GPA) – M-GPA’s 1st five aa’s = Serine-Ser-Thr-ThrGlycine – N-GPA’s 1st five aa’s = Leucine-Ser-Thr-ThrGlutamic 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) 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 Phenotype Genotype S+s- Frequency % Caucasians Blacks SS 11 6 S+s+ Ss 44 24 S-s+ ss 45 68 S-s- S u 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 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 IgG & IgM 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 IgM 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 IgG & IgM Sometimes Anti-s Abs Clinically Significant Abs class IgG Yes Thermal range HDNB Thermal range HDNB 4 - 37 Yes 4 - 37 Yes Transfusion Reactions Transfusion Reactions Extravascular Intravascular Extravascular Intravascular Yes No Yes 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 Phenotype Detectable Antigens Frequencies P1 P1, P 79% P2 P 21% Pk1 P, Pk Rare Pk2 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-P1 Antibodies Naturally occcurring Abs found in the serum of P2 Individuals Anti-P1 Abs Clinically Significant Abs class IgM 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 IgG Thermal range HDNB 4 – 37S Rare IgM Transfusion Reactions Extravascular Intravascular No Yes 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 Abs class IgG Yes Biphasic HDNB Binds at 0 Rare Hemolysis 37 Transfusion Reactions Extravascular Intravascular Rare Yes 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