The ABO Blood Group System PDF

THE ABO BLOOD GROUP SYSTEM Dr SKB Bani 1 2  Each species of animal including human beings have certain inherited antigens on the surface of the rbc which are unique for that species. These are known as isoantigens. Alloantigens are common to some, but not all member of that parti...

THE ABO BLOOD GROUP SYSTEM Dr SKB Bani 1 2  Each species of animal including human beings have certain inherited antigens on the surface of the rbc which are unique for that species. These are known as isoantigens. Alloantigens are common to some, but not all member of that particular species. And are capable of inducing alloantibody production in individuals who do not have it. Blood group serology involves the detection of these antigens and their antibodies. 3  EARLY IN THE 20TH CENTURY, A MOST IMPORTANT DISCOVERY WAS MADE IN BLOOD TRANSFUSION BY KARL LANDSTEINER. HE SHOWED THAT BY CROSS- TESTING ONE BLOOD SAMPLE WITH ANOTHER, SOME WILL MIX SUCCESSFULLY WITH NO VISUAL SIGNS OF REACTION WHILES OTHERS 4 REACT STRONGLY.  THIS AGGLUTINATION WAS ATTRIBUTED TO THE PRESENCE OF AN ANTIGEN ON THE RED CELLS AND AN ANTIBODY IN THE SERUM. IT WAS SHOWN BY THIS EXPERIMENT THAT 2 DIFFERENT RED CELL ANTIGENS EXIST WHICH ARE CALLED ANTIGEN A AND B WITHIN THE ABO GROUPS, IT IS POSSIBLE FOR THE RED CELLS TO HAVE EITHER OF 5 THESE ANTIGENS ON THEIR SURFACE  CELLS THAT ONLY HAVE THE A ANTIGEN ARE CALLED GROUP A, AND THOSE WITH THE B ANTIGEN GROUP B. CELLS THAT HAVE BOTH THE A AND B ANTIGENS ARE CALLED GROUP AB IT IS ALSO POSSIBLE FOR THE CELLS TO LACK BOTH OF THESE ANTIGENS, 6 IN WHICH CASE THE GROUP IS O  IN A SIMILAR WAY TWO DIFFERENT ANTIBODIES EXIST IN THE SERUM, ONE THAT REACTS SPECIFICALLY WITH GROUP A CELLS CAUSING THEM TO AGGLUTINATE IS CALLED ANTI-A, THE OTHER WHICH REACTS SPECIFICALLY WITH B CELLS IN 7 THE SAME WAY IS CALLED ANTI-B  THE PRESENCE OF ANTI-A AND ANTI-B ANTIBODIES IN THE SERUM DIFFERS ACCORDING TO THE AB ANTIGENS PRESENT ON THE RED CELLS. 8 THE BASIC GENETICS OF THE ABO BLOOD GROUPS IN 1924, BERNSTEIN POSTULATED THE EXISTENCE OF 3 ALLELIC GENES A B AND O., AND THAT AN INDIVIDUAL INHERITED TWO GENES ONE FROM EACH PARENT. IT IS THESE GENES THAT DETERMINED WHICH ABO AG WOULD BE PRESENT ON THE PERSON’S ERYTHROCYTES. THE O GENE IS AMORPHIC AS NO DETECTABLE AG IS PRODUCED IN RESPONSE TO THE INHERITANCE OF THIS GENE. 9  EXPRESSION OF THE A AND B GENES ON ERYTHROCYTES OR BODY FLUIDS RESULTS FROM THE INHERITANCE (INDEPENDENT) OF Hh, Sese, AND A AND B GENES, THE LATER ON X’OME 9 AND THE FORMER ON X’OME 19 THE H ALLELE PRODUCES AN ENZYME THAT ACTS AT THE CELLULAR LEVEL TO CONSTRUCT THE H SUBSTANCE, THE PRECURSOR SUBSTANCE ON WHICH A AND B ANTIGENS ARE BUILT 10 INHERITANCE q Strict Mendelian mode of inheritance. q A and B are dominant to O q A and B are co-dominant AO BO AB BO AO OO  THE Se GENE IS RESPONSIBLE FOR THE EXPRESSION OF THE H ON THE GLYCOPROTEINS IN EPITHELIAL SECRETIONS SUCH AS SALIVA THE H GENE CODES FOR THE PRODUCTION OF L-FUCOSYL TRANSFERASE THAT CATALYSES THE ADDITION OF L-FUCOSE TO THE PRECURSOR SUBSTANCE 13  ONCE THE L-FUCOSE HAS BEEN ADDED TO THE PRECURSOR SUBSTANCE, THE H SUBSTANCE IS THUS FORMED IF A PERSON DOES NOT INHERIT AT LEAST ONE H GENE, L-FUCOSE IS NOT ADDED TO THE PRECURSOR SUBSTANCE AND THE H SUBSTANCE IS THUS NOT FORMED. THE A AND B GENES ALSO PRODUCE TRANSFERASES THAT ACT ON THE H SUBSTANCE TO CONVERT IT TO A AND B ANTIGENS 14 RESPECTIVELY  THE A GENE PRODUCES N-ACETYL GALACTOSAMINYL TRANSFERASE AND THE B GENE PRODUCES D- GALACTOSYL TRANSFERASE. THE O GENE HOWEVER DOES NOT PRODUCE ANY TRANSFERASE ENZYME. 15  H antigen THE H ANTIGEN IS THE FOUNDATION UPON WHICH A AND B ANTIGENS ARE BUILT A AND B GENES CODE FOR ENZYMES THAT ADD A SUGAR TO THE H ANTIGEN IMMUNODOMINANT SUGARS ARE PRESENT AT THE TERMINAL ENDS OF THE CHAINS AND CONFER THE ABO ANTIGEN SPECIFICITY A AND B ANTIGEN The “A” gene codes for an enzyme (transferase) that adds N- acetylgalactosamine to the terminal sugar of the H antigen N-acetylgalactosaminyltransferase The “B” gene codes for an enzyme that adds D-galactose to the terminal sugar of the H antigen D-galactosyltransferase Formation of the A antigen RBC Glucose Galactose N-acetylglucosamine Galactose N-acetylgalactosamine Fucose Formation of the B antigen RBC Glucose Galactose N-acetylglucosamine Galactose Galactose Fucose H antigen Certain blood types possess more H antigen than others: O>A2>B>A2B>A1>A1B Greatest amount of H Least amount of H The O allele WHY DO GROUP O INDIVIDUALS HAVE MORE H ANTIGEN THAN THE OTHER GROUPS? THE O GENE IS A SILENT ALLELE. IT DOES NOT ALTER THE STRUCTURE OF THE H SUBSTANCE….THAT MEANS MORE H ANTIGEN SITES  A A A A Group O Group A Many H Fewer A antigen sites H antigen sites Most of the H antigen sites in a Group A individual have been converted to the A antigen SECRETORS AND NON-SECRETORS THE TERMS SECRETOR AND NON-SECRETOR ONLY REFER TO THE PRESENCE OF WATER-SOLUBLE ABH AG SUBSTANCES IN BODY FLUID IT IS INFLUENCED BY THE INDEPENDENTLY INHERITED REGULATOR Se GENE. THE SECRETION OF THE A B AND H ANTIGENS IN BODY FLUIDS IS DEPENDENT ON THE PRESENCE OF THE Se GENE. IT IS PRESENT IN ABOUT 80% OF CAUCASIANS AND FORMS THE BASIS OF MOST CRIME SCENE INVESTIGATIONS 24 TYPE A GROUP A AG’S CAN BE DIFFERENTIATED INTO 2 PRINCIPAL SUBGROUPS A1 AND A2, 80% ARE GROUP A1 AND 20% GROUP A2 IT IS BELIEVED THAT DIFFERENT GENES CODE FOR A1 AND A2. THE SEROLOGIC DISTINCTION BETWEEN A1 AND A2 IS BASED ON THE REACTIONS OF ERYTHROCYTES TO VARIOUS ANTISERA. 25REAGENT ANTI-A SERA FROM HUMAN TYPE A IF ANTI-A FROM A GROUP B PERSON IS ADSORBED WITH A2 CELLS, A TYPING SERUM CAN BE PREPARED THAT WILL AGGLUTIUNATE A1 BUT NOT A2 ERYTHROCYTES FOR ROUTINE BLOOD TRANSFUSION HOWEVER, IT IS NOT NECESSARY TO DISTINGUISH BETWEEN A1 AND A2 EXCEPT WHEN WORKING WITH A2 OR A2B INDIVIDUALS WHOSE SERUM CONTAINS ANTI-A1 26 TYPE B SUBGROUPS OR VARIANTS OF TYPE B BLOOD ARE NOT AS COMMON AS THOSE OF A. THERE ARE THREE SUBGROUPS;CLASSIFICATION WAS DONE BY RACE AND SANGER QUALITATIVE AND QUANTITATIVE DIFFERENCES EXIST IN THE B AG. 27 28 29 GROUP ANTIBODY IN SERUM A1 ANTI-B A2 ANTI-B, ANTI-A1 IN UP TO 2% A1B NONE A2B ANTI-A IN UP TO 25% THE A2 IS WEAKLY REACTING AND THEREFORE NOT IMPORTANT IN SELECTING BLOOD FOR TRANSFUSION. OTHER A SUBTYPES INCLUDE A3, Aend,Abantu, AX etc. A 30bantu ITS FREQUENCY IS HIGHEST IN THE KHOSIAN PEOPLE OF SOUTH AFRICA ABNORMALITIES ENCOUNTERED IN THE EXPRESSION OF ABH ANTIGENS ON ERYTHROCYTES MODIFYING GENES ACQUIRED ANTIGENS ALTERED ANTIGENS HIGH LEVELS OF SOLUBLE ABH SUBSTANCES DEPRESSION OF A B AND H ANTIGENS IN DISEASE MIXTURES OF BLOOD 31 MODIFYING GENES IN SOME AB PEOPLE WITH RELATIVELY FEW A ANTIGEN SITES ON THE ERYTHROCYTES, THE DEFICIT OF A ANTIGEN IS BELIEVED TO BE CAUSED BY THE PRESENCE OF A SUPERACTIVE B TRANSFERASE. THIS IS CODED FOR BY A SUPERACTIVE B GENE THAT COMPETES WITH A1 OR A2 TRANSFERASE 32  ON RARE OCCASIONS A AND B ANTIGENS DEVELOP IN THE ABSENCE* OF H SUBSTANCE. LEVINE HYPOTHESISED THAT THIS WAS CAUSED BY A PARTIAL SUPPRESSOR AT THE Hh LOCUS THAT PREVENTED NORMAL QUANTITIES OF H SUBSTANCE FROM BEING PRODUCED. SOME INVESTIGATORS THEORISED THAT AN ALTERNATIVE PATHWAY EXISTS FOR THE FORMATION OF A ANTIGENS (AND PERHAPS 33 B) ACQUIRED ANTIGENS ACQUIRED A ANTIGEN HAS BEEN REPORTED IN PERSONS OF TYPE O OR TYPE B IN ASSSOCIATION WITH SEVERE SEPTIC INFECTIONS CAUSED BY PROTEUS MIRABILIS IN THESE CONDITIONS REACTIONS WITH ANTI-A REAGENT ARE VISIBLE MICROSCOPICALLY AS MIXED FIELD 34 AGGLUTINATION.  ACQUIRED B-LIKE ANTIGEN WAS FIRST RECOGNISED IN 1959 WITH CONDITIONS SUCH AS CA COLON, INTESTINAL OBSTRUCTION AND SEPTICAEMIA CAUSED BY PROTEUS VULGARIS. AFTER RECOVERY FROM THE INFECTION OR CONDITION,THE ACQUIRED B-LIKE ANTIGEN IS LOST AND THE PATIENT RETURNS TO NORMAL BLOOD STATUS 35THIS PHENOMENON IS INFREQUENTLY  THE ACQUISITION OF B ANTIGEN USUALLY OCCURS IN PERSONS WITH THE A1 PHENOTYPE DEACETYLATION OF THE A1 ANTIGEN BY BACTERIAL ENZYMES CAUSES A CHANGE 36 IN THE ANTIGEN. HIGH LEVELS OF SOLUBLE ABH SUBSTANCES OCCURS IN CONDITIONS LIKE OVARIAN CYSTS, INTESTINAL OBSTRUCTION, AND CA OF THE STOMACH AND PANCREAS. LEVELS MAY BE SO HIGH AS TO INHIBIT THE ANTI-A OR ANTI-B REAGENT THERE IS NEUTRALIZATION OF THE REAGENT ANTI-A OR ANTI-B BY THE SPECIFIC SOLUBLE SUBSTANCES, LEAVING NO UNBOUND ANTIBODIES TO 37 REACT WITH THE PERSONS DEPRESSION OF A, B AND H SUBSTANCES WEAKENING OF THE A ANTIGEN HAS BEEN NOTED IN PATIENTS WITH LEUKAEMIA AND LYMPHOMA. THE B AND H ANTIGENS CAN ALSO BE DEPRESSED BUT IN SOME CASES AS THE LEVEL OF A OR B ANTIGEN DECREASES, THE LEVEL OF H ANTIGEN DETECTABLE ON THE ERYTHROCYTES INCREASES. 38 OTHER BLOOD GROUP ANTIGENS 39 OTHER BLOOD GROUP SYSTEMS These are of little clinical importance. Although naturally occurring antibodies of P, Lewis and MN system are not uncommon, they usually only react at low temperatures and hence are of no clinical consequence. Immune antibodies are detected infrequently and antigens are of low immunogenicity and are of no clinical importance  MNSs Feature Comments ISBT Number 002 First described MN: 1937 by Landsteiner and by/system established Levine by S: 1947 by Walsh and Montgomery s: 1961 by Levine Antigen symbol MNS OMIM number MN + 111300 Ss + 111740 Composition/type Protein Genes MN: GYPA Ss: GYPB Chromosomal 41 location 4q28-q31 Anchorage MN carried on glycophorin A  MNSs Incidence White people: M+N-28% M+N+50% M-N+22% S+s-11% S+s+44% S- s+45% Antibody characteristics MN reacts at temp up to 20oC, though some examples may react up to 37oC. Do not readily activate complement Ss capable of activating complement and are usually reactive at Clinical significance 37 oC MN normally considered to have little clinical significance, unless they react at 37 oC 42 Ss clinically significant, have been implicated in transfusion reactions and HDN  MNSs Disease associations Resistant to Plasmodium falciparum invasion and receptor of some E. coli Considered function Act as receptor for complement, bacteria and viruses GPA enhances the rate of folding and maturation of band 3 Major component contributing to the negatively Tissue distribution: charged Renal endothelium and RBC glycocalyx epithelium 43  Kell Feature Comments ISBT Number 006 First described Indentified by Weitkamp et at (1975) by/system using an antibody developed by Mrs Kell established by through the mechanism of materno- foetal incompatibility Antigen symbol KEL OMIM number 110900 Composition/type Zinc metallglycoproteins with neutral endopeptidase activity Genes K, k, Kpa, Kpb, Jsa and Jsb Chromosomal 7q33 location 44 Anchorage Resides on a 93kD membrane  Kell Incidence K: 9% in English population and 3% in Black population Kpb: 99.9% in Caucasian population Jsa: