Presentation on theme: "Other Blood Groups Lewis, Kell, Duffy, Kidd, Ii, MNSs & P"— Presentation transcript:
1 Other Blood Groups Lewis, Kell, Duffy, Kidd, Ii, MNSs & P
2 Introduction Over 500 blood group antigens “High incidence”, “public” or “high frequency” antigens are those present on almost every person’s red blood cells“Low incidence”, “private” or “low frequency” antigens are present on very, very few individuals red blood cells
3 IntroductionEach known antigen initially identified through the detection of its specific antibody in the serum.Knowledge of serologic behavior and characteristics of blood group antibodies is CRITICAL for identification
4 IntroductionEssential when evaluating antibody screen and panel studies.Considerations given to:Phase of reactivityAntibody class involvedAbility to cause HDFN and HTR
5 Major Blood Group Systems LewisIPMNSsKellKiddDuffy
6 Lewis SystemMajor antigens Lea and Leb , other antigens include Lec, Led and LexAntigens ARE NOT intrinsic to RBCs but are absorbed from the plasma and inserted into RBC membrane.
8 Lewis System Antigenic Development Genetic control reside in single gene “Le”Amorph le, if homozygous will not have Lewis antigensLea formed first, then modified to form Leb which is adsorbed preferentially over LeaLewis phenotype of RBC can be changed by incubating with plasma containing Lea or Leb glycoplipid.
9 Lewis System Lewis Phenotypes and Their Frequencies White Black Le (a+b-)22%23%Le (a-b+)72%55%Le (a-b-)6%Le (a+b+)Rarerare
10 Lewis System Lewis antigens in infants Antigens absent or extremely weak at birthExpression of Leb gradualBirth Le (a-b-)2 months Le(a+b-)12 to 18 months Le(a+b+)2 to 3 years Le (a-b+)
11 Lewis System Lewis antigens and pregnancy Antigen strength may decline dramaticallyTransiently Le (a-b-) may produce Lewis antibodies during pregnancyAntigens return after delivery and antibodies disappear
12 Lewis System Interaction of Le, Se and H Genes lele will not have Lewis antigens, but if Se present will have A, B and H in secrectionsGenotype se/se and have one Lewis antigen will have Lea in their secretions but no A, B or H.
14 Lewis System Le (a+b-) Le (a-b+) Le (a-b-) Lewis Phenotype ABH SecretorLewis SecretorLe (a+b-)All ABH NON-SecretorsAll Lea SecretorsLe (a-b+)All ABH secretorsAll secretors of Lea and LebLe (a-b-)80% ABH secretors20% ABH NON secretorsNONE
15 Lewis System Lewis Antibodies Almost always IgM, react strongly at RT, may cause ABO discrepancy if reverse cells have Lewis antigen.Occur almost exclusively in Le (a-b-) and production of anti-Lea AND –Leb not unusualAnti-Lea frequently encountered, anti-Leb rarely encountered.
17 Lewis System Lewis Antibodies Although most react at RT reactivity may be seen at 37C, but is weaker and may be weakly reactive at AHGCan bind complement and cause IN-VITRO hemolysis, most often with enzyme treated cellsBecause antibodies are IgM and antigens are poorly developed at birth antibodies NOT implicated in HDFN.
19 Lewis System Lewis antibodies Can be neutralized in-vitro by additions of Lewis SubstanceLe antigens are present in secretionsAdd to serum with Lewis antibodies and the antibodies will be bound to the soluble Lewis antigensUseful when multiple antibodies are present and 1 is a Lewis, eliminates the activity of the antibody
20 Lewis Antibodies Anti-Le a, Anti-Le b, Anti-Lex Most react at room temperature or below -Often fix complementSome in vitro hemolysisLe a may cause HTR
21 Lewis Antibodies Anti-Le a Found in Lea-b- secretors best room temperature or belowOften fix complementSome in vitro hemolysisLe a may cause HTR
22 Lewis Antibodies Anti-Le b Often found with Anti-Lea Most react at room temperature or belowTwo types - Anti-LebH and Anti-LebLRare cause of HTR
23 Lewis Antibodies Anti-Lex Most react at room temperature or below - Reacts with both Lea and Leb as a single antibody
24 Lewis Antibodies Special Problems in the Blood Bank Lewis antigens may be weaker during pregnancy and women produce antibodiesCan neutralize Lewis antibodies with Lewis plasmaPregnant woman with room temperature antibodies, neutralize with Lewis antigen when testing for HDN antibodies
25 Lewis System Transfusion Practice Transfused RBCs will acquire the Lewis phenotype of the recipient within a few daysLewis antibodies in patient will be neutralized by Lewis substance in donor plasmaLewis antibodies rarely cause in-vivo hemolysisIt is not necessary to phenotype donors for Lewis antigens prior to transfusion, give crossmatch compatible
27 Background 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.
28 Molecular 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.
30 Kell 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
31 XK Gene (Chromosome X) KEL Gene RBC Kx Kell system glycoprotein: Kell Ag’s reside here.Kx
32 Frequency of Kell phenotypes CaucasiansBlacksK-k+91 %98 %K+k-0.2 %RareK+k+8.82
33 Kx 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
34 McLeod PhenotypeAbsence of Kx proteins in RBCs membrane lead to McLeod PhenotypeThis absence cause:abnormal RBCs shape (acanthocytes)& reduced in-vivo survival
35 Chronic 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 CGDcells of the immune system have difficulty forming the reactive oxygen compounds (most importantly, the superoxide radical) used to kill certain ingested pathogens
37 Kell 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
38 Kell Antibodies K- individuals produce anti-K when exposed to K+ cells Frequency of K+ is low (9%), easy to find bloodOn the other hand frequency of k is 99.9%k- individuals produce anti-k when exposed to k+ cellsDifficult to find blood
39 Antibodies produced against Kell antigens Kell AbsClinically SignificantYesAbs classIgG (rarely) IgMThermal range4 - 37HDNBTransfusion ReactionsExtravascularIntravascularRareHDN: Antigen is present on fetal cells as early as 10 weeks gestation
41 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 proteinFive alleles at Duffy locus, the most important: Fya, Fyb & Fy (Silent Allele)Fya is more immunogenic than Fyb
44 Different 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 populationsa mutation in the promoter region of the FYB allele abolishes the expression of the Duffy glycoprotein in RBCs, but the protein is still produced in other types of cells. these patients do not generally make anti-Fyb or anti-FyaLess commonly, the Fy(a-b-) phenotype is a result of point mutation that introduces a premature stop codon into the coding sequence. It is unlikely that the truncated Duffy protein is transported to the cell surface, and it is likely that the Duffy protein would be absent from all tissues in individuals who carry this type of mutation.
45 Duffy Antigens Fya, Fyb antigens are Destroyed by enzymes Abs DO NOT agglutinate enzyme treated cellsModerately immunogenicFya is more immunogenic than Fyb
46 Clinically 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
47 Duffy 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
50 Kidd 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.
52 Phenotype Frequencies What is the purpose of learning the phenotype frequencies of each blood group antigen?When crossmatches are required it helps the Tech know how many units to crossmatch or antigen type to find compatible blood.If a patient has anti-Jka antibody how many RBC units need to be antigen typed to find 2 compatible units?78% of the population is positive for the antigen therefore 22% are NEGATIVE for the antigen. Approximately 2 out of 10 units are compatible. Need to antigen type 10 units.
53 Kidd 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
55 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.
56 Ii Antigens Little i antigen is LINEAR Big I antigen is BRANCHED 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 cells
58 The 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
59 Clinically 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
60 Antii 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
61 MNSs 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.
62 MN 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
64 MN Genotypes & Phenotypes Frequency %M+N-MM30M+N+MN50M-N+NN20
65 MNSs AntigensM & N only differ in their amino acid sequence at positions 1 and 5MGlycophorin ANRBCS & s only differ in their amino acid sequence at position 29SUsGlycophorin BCOOH end …..….5, 4, 3, 2, 1 (NH2 end)
66 Ss Genetics Ss genes code for the production of Glycophorin B(GPB) S glycophorin B has Methionine at aa position 29s glycophorin B has Threonine at aa position 29Glycophorin B (GPB) is a glycoprotein also known as Ss-sialoglyprotein
67 Ss 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.
68 Rare Alleles Rare low incidence alleles found on MN locus Some may result from crossing over of genes of glycophorin A & BSuch crossing over results in hybrid sialoglycoproteins
69 Clinically Significant Transfusion Reactions Anti-M AntibodiesVariability of reactivity (Dosage)Strong reactions with RBCs homozygous for MMWeak reactions with RBCs heterozygous MNAnti-M AbsClinically SignificantSeldomAbs classIgG & IgMThermal range4 – 22Rare 22-37HDNBrareTransfusion ReactionsExtravascularIntravascularRareNo
70 Clinically Significant Transfusion Reactions Anti-N antibodiesAnti-N AbsClinically SignificantNoAbs classIgMThermal range4 - 22HDNBTransfusion ReactionsExtravascularIntravascularNaturally occurring cold agglutininCan form in patients with renal FailureDuring dialysis with formaldehyde sterilized equipmentFormaldehyde may alter the N Ag structure making it appear foreign
72 P 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
73 Phenotypes, 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.
74 Clinically Significant Transfusion Reactions Anti-P1 AntibodiesAnti-P1 AbsClinically SignificantoccasionallyAbs classIgMThermal range4 – 22Rare 22-37HDNBNOTransfusion ReactionsExtravascularIntravascularNoRareNaturally occcurring Abs found in the serum of P2Individuals
76 Allo Anti-P Antibodies Allo Anti-P AbsClinically SignificantYesAbs classIgMRare IgGThermal range4 – 37SHDNBRareTransfusion ReactionsExtravascularIntravascularNoNaturally occcurring Abs found in the serum of Pk and pIndividuals
77 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 AbsClinically SignificantYesAbs classIgGBiphasicBinds at 0Hemolysis 37HDNBRareTransfusion ReactionsExtravascularIntravascular