BLOOD GROUPS

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Definitions
Blood groups are determined by antigens structures on the surfaces or red cells and are detected by reactions with specific antibodies. A blood group system is defined by a.g that are regulated either by allelic genes or closely linked genes.
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The number or red cell blood groups now exceeds 400. (table1). Table 1. Survey of major Red Cell Blood Group System System Important antigens
ABO MNSs P Rh Lutheran Kell Lewis Wright Diego Cartwright Xg Dombrock Colton
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A1,A2,B,H,A3,Am,Ax M,N,S,s,U,Mg,Mia,Hu,HeMta,Vw,M2,N2,S2 P1,pk,P2,(Tja) D,C,E,c,e,Cw,Ew,ce,Ce,G,CE,cE,Du,Cu,Eu,LW Lua,Lub K,k,Kpa,Kpb,Jsa,Jsb Lea,Leb Wra,Wrb Dia,Dib Yta,Ytb Xga Doa,Dob Coa,Cob
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Antibodies : sources & properties

1. Normal humans

A.bodies to some blood group a.g occur in the serum of individuals who lack the a.g and have had no prior exposure to it natural isohemagglutinins.
The major ones are directed against surface a.g such as the ABO, Ii and P systems controlled by oligosaccharides
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Isohemagglutinins with ABO are always

clinically significant Isohemagglutinins elicited by similar sequences on microbial surfaces >>Ig Ms effective hemolysins because they efficiently fix complement. Occasionally Ig G a.bodies specific for these a.g also appear.
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2. Immunized animals
If animals are immunized with human red cells may form a.bodies to certain of the xenogeneic blood group a.g important source of blood group anti sera carefully absorbed with human red cells to establish specificity. Recently developed a.g specific monoclonal a.bodies do not require such absorption.
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3. Immunized humans
The third major source of the blood group anti

bodies are donors who have been allogenically

immunized either by (1) prior blood

transfusions or (2) previous pregnancies

immune antibodies elicited by prior

exposure to red cell a.g are commonly IgGs

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Methods of detection
1. Agglutination by specific antibody Under physiologic conditions of pH and ionic strength, normal red cells repel each other owing to their negative surface charge or zeta potential 2. Enhancement of agglutination by antibody a. Reduction of zeta potential Can be reduced by addition of colloid (alb, polyvinylpyrrolidone or dextran).
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b. Insertion of a.b red cells bridges Agglutinations may produced or enhanced

by addition of Coomb reagent (i.e.,antiglobulin a.body)

3. Use of lectins
4. Automated techniques

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Genetics
According to mendelian laws Heredity is generally autosomal codominant i.e there is an expression of both alleles in the heterozygous individual 1.Linked genes 2.Interaction with other genes 3.Loci of blood groups genes on chromosomes (table 2) 4.Occurrence of blood group antigens
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Table 2. Chromosome Assignment of Some Blood Group Loci Locus ABO Rh Fy Chido, Rogers MNSs Xg Sc
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Chromosome 9 1 1 6 4 X 1
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ABO SYSTEM
a. Historical notes In subsequent work Landsteiner recognized that the pattern of reactions could be explained by two a.g, which designated A and B. O signified the state of not having A or B.
Table 3. The Landsteiner scheme

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Table 3. The ABO system defined by Anti-A and Anti B

Blood Groups O A B AB Antigens on RC None A B A and B Antibodies in serum Anti-A and Anti-B Anti-B Anti-A None

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b. Subdivisions of A antigen
A antigen and anti-A are complex. Anti-A serum from a group B donor contains 2 types of a.b, anti-A and anti-A1 . (table 4)
Group Antigens Reaction with Anti-A + + Anti-A1 + -

A1 A2

AA1 A

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Genetics Determining the blood group : genotype and phenotype. A child receives one of four genes from each parent : A1, A2, B1, or O. Six phenotypes are possible because the A a.g associated with group A2 and also A1. There are ten possible genotypes. Group A1 may have 3 genotypes (A1 A1, A2 O, A1A2). Group A2 can have either A2A2 or A2 O genotypes. Group B can have either BB or BO genotypes
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 Genotype : - specific genes that person carries

- determined by family studies

- AA, AO, BB, BO, AB and OO

- see fig 1.

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Family 1

Phenotype Genotype

B BO

A1 A1O

Phenotype Genotype

O OO

O OO

A1B A1B

Family 2

Phenotype Genotype

A1 A1A2

A2B A2B

Phenotype Genotype

A2B A2B

A1 A1A2

Fig 1. Illustration of usefulness of family studies in the elucidation of phenotype

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Phenotype :
Four phenotypes : A, B, AB and O

Although there are ten possible genotypes,

the absence of a specific anti-O prevents the

serological recognition of more than four

phenotypes. (table 5)

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Table 5. Blood Type

Phenotype Genotype Antigens on red cell Antibodies in plasma

O A B AB

OO AA or AO BB or BO AB

O A B AB

Anti-A, Anti-B Anti-B Anti-A None

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Fig.2 Synthesis of ABH antigens

R
glc gal glcnac Hh gen gal H precursor

fuc R glc gal glcnac gal H antigen

A gene

B gene

fuc R glc
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fuc R glc gal glcnac gal B antigen gal

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gal

glcnac gal A antigen

glcnac

H antigen
The surfaces oligosaccharides that

constitutes the H a.g is the precursor of the

A and B a.g Gene A & B responsible for converting H substance into A & B substance The O gene is an amorph and doesnt transform the H substance
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Rare variant Bombay, the H precursor

cannot be converted to H lack H ag & hence A or B phenotype cant be expressed. A terminal sugar molecules determine a.g specificity : A a.g : N acetylgalactosamine B a.g : galactosa

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Other Carbohydrate Antigen

a. Lewis system

The Lewis a.g are made from the same precursors as the ABH a.g except that they are exclusively type 1 chain.
The expression ag depends on the interaction of the H gene, Se gene and Le gene
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b. P system
These ag were recognized by antisera developed in rabbits glycosphingolipids and originate on a ceramide dihexose (GalGal-ceramide)

c. Ii system
Most cold a.bodies have specificity against the Ii a.g system. These a.g are found in red cells and nonhematopoietic tissue
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Rhesus System

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Rhesus a.b >> immune (previous transfusion or pregnancy), naturally << Anti-D is responsible for most of the clinical problems associated with the system the simple subdivision of subjects into Rh D + and Rh D , using anti-D is sufficient for routine clinical purposes.

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A. Nomenclature : relation to genetic models

1. Fischer-Race theory (table 6) : Postulates 3 closely linked genes Cc, Dd and Ee. Rhesus a.g is renamed D. Rhesus positive presence of the D antigen, also called Rh or Rh factor Rhesus negative absence of D but doesnt denote absence of other a.g of the Rh system (C,c,E or e)
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B. C.

D. E.

2. Weiner system 3. Rosenfield system Compound antigens Weakened antigens : - weakly reactive ag Du - formal terminology : Rh +, Du variant - for transfusion : Du is equivalent to Rh + Deleted antigens : Rh null cells. Rh antigens structure
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Table 6. Rh gene complexes

Fischer-Race CDe cde cDE cDe CwDe cdE Cde CDE Wiener R1 r R2 Ro R1W ru r1 Rz

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Other clinically significant systems

1. Kell system The Kell a.g system rivals the Rh system in its complexity and clinical importance. Appearing in response to prior immunization, anti-Kell a.b have caused hemolytic transfusion reactions and HDN. The main a.g pairs : K-k, Kpa-Kpb and Jsa-Jsb 2. Duffy system Double negative phenotype red cells, Fy (a-b-) are totally resistant to invasion by Plasmodium vivax. Transfusion of incompatible blood into Duffysensitive individuals can cause severe hemolysis.
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3. Kidd system Immunization to Kidd is caused mainly by transfusions. Kidd a.b are evanescent warm-active incomplete a.b that may not be detected in red cell a.b screens. Consequently they often cause delayed transfusions rx, which may be severe.

4. Lutheran system
There are 2 common alleles, Lua and Lub and a silent one. The double-negative phenotype caused by either dominant inhibitor gene or a recessive silent allele.
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5. Xga blood group This a.g is controlled by a gene on the X chromosome. Its not clinically significant but is of interest as a marker for X chromosome that appear to escape inactivation by the Lyon mechanism.

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The ABO and Rhesus (Rh) groups are of major clinical significance. Some other systems of less overall importance are listed in table 7.
Systems ABO Rh Kell Duffy Kidd Lutheran Lewis P MN Ii
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Frequency of a.body Very common Common Occasional Occasional Occasional Rare Occasional Occasional Rare Rare

Cause of HDN Yes Yes Yes Yes Yes No No Yes (rare) Yes (rare) No
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Uses of blood grouping data

A. In clinical medicine

1. Pretransfusion testing :
Prior to transfusion, blood is typed

and crossmatched to establish ABO and

D compatibility

2. Hemolytic disease of the newborn

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B. In genetics chromosome mapping

C. In forensic medicine :

1. Identification studies
2. Paternity testing

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Thank you

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