REDBLOODCELLANTIGENS

HISTORY OF TRANSFUSION

1665 The first recorded successful blood transfusion occurs in England: Physician Richard Lower keeps dogs alive by transfusion of blood from other dogs.

1667 Jean-Baptiste Denis in France and Richard Lower in England separately report successful transfusions from lambs to humans. Within 10 years, transfusing the blood of animals to humans becomes prohibited by law because of reactions.

1795 In Philadelphia, American physician Philip Syng Physick, performs the first human blood transfusion, although he does not publish this information.

CONTD..

• 1818 James Blundell, a British obstetrician, performs the first successful transfusion of human blood to a patient for the treatment of postpartum hemorrhage. Using the patient's husband as a donor, he extracts approximately four ounces of blood from the husband's arm and, using a syringe, successfully transfuses the wife. Between 1825 and 1830, he performs 10 transfusions, five of which prove beneficial to his patients, and publishes these results. He also devises various instruments for performing transfusions and proposed rational indications.

• 1840 At St. George's School in London, Samuel Armstrong Lane, aided by consultant Dr. Blundell, performs the first successful whole blood transfusion to treat hemophilia.

At the beginning of the 20th century an Austrian scientist, Karl Landsteiner, noted that the RBCs of some individuals were agglutinated by the serum from other individuals. He made a note of the patterns of agglutination and showed that blood could be divided into groups. This marked the discovery of the first antigens present on red cell surface..“The red cell antigens”

ANTIGENA substance that can cause an immune response , when recognised as foreign to body.

RED CELL ANTIGENSThese are like any other antigens i.e capable of causing immune response when foreign to body.Red cell antigens are naturally occuring antigens on red cell surfaceThere are over 400 red cell antigens discovered tell date.These are sugars or proteins or both.

CLASSIFICATION OF RED CELL ANTIGENS

According to terminology given by international society of blood transfusion(ISBT).

1.Blood group systems2.Collections3.Series

Blood group system

• A blood group system contains antigens controlled by a single gene(or by multiple closely linked loci),the system is genetically distinct.

• There are 29 blood group systems.• According to ISBT each antigens is assigned a 6

digit number, first 3 digits represent blood group system and next three identify antigen. e.g:-antigen -A is represented as 001001.

COLLECTIONS

• A COLLECTION CONTAINS ANTIGENS THAT ARE RELATED IN SOME WAY , AS BY GENETICS OR BIOCHEMISTRY,BUT DO NOT THE CRITERIA TO FORM A BLOOD GROUP.ONCE A COLLECTION OF ANTIGENS CAN BE PROVEN GENETICALLY DISTINCT ,THEY ARE GIVEN THE STATUS OF BLOOD GROUP .THERE ARE 6 COLLECTIONS

SERIES

• Red cell antigens that do not fit in blood group or collections are sorted into 2 series ; if there frequency is low i.e <1% ,they are placed in series 700; if there frequency is more than 90% they are placed in 901 series.

• There are 22 antigens in 700 series and 11 antigens in 901 series.

ABO BLOOD GROUP SYSTEM

• It was first system to be discovered in the year 1900 by austrian scientist karl landsteiner;he earned a nobel prize for this.

• Till date it is the most imp. System ; due to higher potency of its antigens and naturally occuring antibodies

No. of antigens:- 4 A , B ,AB ,A1

Antigen specificity:-carbohydrate sequence of oligosaccharide determines whether antigen is A ,B or A1

Antigen carrying molecule:- glycoproteins or glycolipids of unknown function . the ABO blood group antigens are attached to oligosaccharide chains that project above the RBc surface.these chains are attached to proteins and lipids that lie in the rbc membrane.

Molecular basis:- the ABO gene indirectly encodes for allelic forms A,B and O.The ABO locus has three main allelic forms A , B and O. the A and B alleles each encode a glycosyltransferase that catalyses the final step in the synthesis of A & B antigens, here the H-antigen is modiefied to give A orB antigen by the action of A or B transferases respectively.A transferases differ from B transferases by 4 a.acids. The o allele encodes for inactive glycosyltransferase that leaves the h antigen unmodified.

Genetic basis:- ABO locus is located on chromosome 9.A and B allele differ from each other by 7 nucleotides.the O allele differ from A allele by the deletion of guanine at position 261.There are many variants ABO allele that encode no. of variant ABO phenotype.for example weak A subgroups like A3,Ax and Ael and weak B subgroups like B3 and Bx express b antigen.

A gene causes N-acetyl-galactosamine to be added to H substance, producing A antigen

B gene causes D-galactose to be added to H substance, producing B antigen.

H ANTIGEN• IT IS A PRECURSOR SUBSTANCE FOR THE FORMATION OF A AND B

ANTIGEN.• SPECIFICITY OF H ANTIGEN IS DETERMINED BY THE SEQUENCE OF

OLIGOSCCHARIDES FUCOSE-GALACTOSE.• IT IS PRESENT ON 99.9% RBCS OF ALL POPULATION.ITS DEFICIENCY

IS KNOWN AS BOMBAY PHENOTYPE.• ISBT SYMBOL:-018• H ANTIGEN LOCUS IS LOCATED ON CHROMOSOME 19.ITS

BIOSYNTHESIS INVOLVES SERIES OF ENZYMES (GLYCOTRANSFERASES)THAT TRANSFER MONOSASSHARIDES.THE RESULTING ANTIGEN IS CHAINS OF OLIGOSACCHARIDE ATTACHED TO LIPIDS AND PROTEINS THAT ARE ANCHORED IN THE RBC MEMBRANE.

EXPRESSION

• ABO anigens are not only expressed on rbcs but on majority of other tissues.

• In individuals who are secretors antigens are found in saliva and all bodily fluids.

• There are 200 million molecules of ABO blood group antigens

NOMENCLATURE

• As given by ISBT • Symbol :-ABO• Number:-001

RH BLOOD GROUP SYSTEM

No of antigens:-49D,C,E,c and e are clinically important

Antigen specificity:-proteinThe sequence of amino acids determine the specificity of Rh antigen

The antigen carrying molecule:-protein of unknown functionThe RhD and RhCEproteins are both transmembrane,that are integral

to rbc membrane.the Rh proteins are not glycosylated but are closely associated with rbc membrane glycoprotein called RhAG.the function of rh protein is the transportation of ammonia and carbon-dioxide.

Molecular basis:- the rh locus is located on long arm of chromosome 1 and it contains gene RHD and RHCE, which lie in tendem.The genes encode for transmembrane proteins that are 4oo a.acids in length and transverse rbc membrane 12 times.RhD protein differs from RhCE protein by 35 a.acids.the RhD protein bears the d antigen which has over 30 epitopes.the RhCE carries epitopes for C or c antigen on the second extracellular loop and the epitope for E or e antigen on 4th extracellular loop.

Weak d (Du)In this all D antigen epitopes are present but are underexpressed. Du is a Rh phenotype found in less than 1% of people.it is typically caused by single a.acid switch in the transmembrane regionof the RhD protein.this disrupts how the RhD protein is inserted into the rbc membrane, reducing the level of expression of RhD.

EXPRESSIONThe rh antigens are expressed as a part of a protein complex in the rbc membrane.these antigens are only expressed on the cells of erythroid lines.compesition of complx is unknown but is thought to be a tetramer.

Nomenclature as by ISBT:Symbol:-RhNumber:-004

THE KELL BLOOD GROUP SYSTEM