Abo Blood Group System 381748
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ABO blood group system Use ABO system, as major example to discuss discovery, inheritance, basic biochemistry of antigens and clinical significance of blood group antibodies.
Overview.
• Genetics • Inheritance. • ABO,Hh,Sese locus.
• Antigens. • Antibodies.
• Clinical Significance. • Subgroups A1 and A2. • Geographic distribution.
ABO Blood Groups. • 1900 Austria Karl Landsteiner • Mendelian inheritance of A, B or O gene. • One from each parent. • A and B genes co-dominant. • O gene amorphic. http://www.nobelprize.org/nobel_prizes/medicine/laureates/1930/landsteiner-bio.html
Phenotype
Genotype
O
OO
A
AA, AO
B
BB, BO
AB
AB
ABO Inheritance. Parents group A and B A A B AB AB B AB BB
A O B AB BO O AO OO
Parents group A and A A A A AA AA A AA AA
A O A AA AO A AA AO
A B AB B AB
O BO BO
A O A AA AO O AO OO
Gene Action Three Loci: FUT1, FUT2, ABO
Genes code for production of specific glycosyltransferases Enzymes transfer immunodominant sugars from donor molecules to preformed oligosaccharide chain thus changing the antigen specificity.
ABO locus • ISBT No: 001. • Symbol: ABO. • Gene name: ABO. • Chromosome: 9 • Gene products: • n-acetyl galactosaminyltransferase. • D-galactosyltransferase • Converts H to A, B antigen. • Sugar donor: UDP.
FUT1 (Hh) locus • ISBT No: 018. • Symbol: H. • Gene name: FUT1. • Chromosome: 19 • H dominant, h amorph. • Gene product: fucosyltransferase. • Converts basic precurso substance to H antigen. • Sugar donor: GDP.
FUT2 (Sese) locus Chromosome 19
•"Secretors" (SeSe or Sese) secrete type 1 precursor substance. •Se dominant, se amorphic. •Encodes a fucosyltransferase expressed in epithelia of secretory tissues. •Production of H antigen in secretions.
Type II Red Cell Surface D-galactose N-acetylglucosamine N-acetyl-D-galactosamine
L-fucose
β-1,4
Type I
β-1,3
Precursor substance
H Antigen L-fucosyltransferase Type I
Type II Red Cell Surface D-galactose N-acetylglucosamine N-acetyl-D-galactosamine
L-fucose
A Antigen N-acetyl galactosaminyltransferase
Red Cell Surface D-galactose N-acetylglucosamine N-acetyl-D-galactosamine
L-fucose
B Antigen
D-galactosyltransferase
Red Cell Surface D-galactose N-acetylglucosamine N-acetyl-D-galactosamine
L-fucose
ABH null phenotype Oh H H h
H H H
H h H
H H h
H h H
Phenotype Genotype
h h h
Genotype Phenotype
No H – no ABO antigens Anti-H, anti-A, anti-B and anti-A,B in serum Transfuse only with blood from Oh donor. 1952, Bhende YM et al
Antibodies Produced 4-6 months after birth.
IgM -“naturally IgG -
occurring” Activate complement and cause severe HTR.
Immune anti-A,B in group O
Can cross placenta and cause mild to moderate Haemolytic Disease of the Foetus and Newborn.
Group O serum anti-A,B. • Higher IgG component. • High titre group O donors.
• antibody reacts clearly at a 1:10 dilution. • not used for plasma products.
• Not simple mixture of anti-A and anti-B.
Group O serum Absorption and elution studies
u
u
Eluate + group A cells
Elution Anti-A,B + group B cells.
Inhibition studies.
Eluate.
Eluate + group B cells
Saliva from group A or B secretors inhibits reaction of anti-A,B with A or B cells.
Transfusion practice
ABO group A
Antibodies in plasma Anti-B
Compatible donor ABO blood group A, O and Oh
B
Anti-A
B, O and Oh
AB
None
AB, B, O and Oh
O
Anti-A, anti-B, O and Oh (anti-A,B) Oh Anti-A, anti-B, Oh only (anti-A,B), anti-H Donor blood must be crossmatched before transfusion.
Subgroups A1 and A2 80% of group A individuals are A1, 20% A2 Anti-A1 Anti-A Anti-H
A1 cells 4 4 1
A2 cells 0 2-3 3
Quantitative difference A1
8-12 X 105 A antigens
A2
1-4 X 10
5
,,
A1 and A2 Qualitative difference • 2% of A2 have anti-A1 as well as anti-B; • 25% of A2B have anti-A1
• NB. Anti-A2 does not exist!
Amount of H antigen in ABO blood groups O>A2>B>A2B>A1>A1B
Geographical distribution
Frequencies-(A and A ) 1
2
Summary.
• Mendelian Inheritance.
• A & B co-dominant, O amorph. • Three loci involved ABO,Hh,Sese. • Carbohydrate antigens • Glycosyltransferases • Antibodies mostly complement activating IgM + low level IgG. Group O serum. • Acute HTRs and mild HDFN. • Subgroups A1 and A2 differences. • Geographic distribution.
Further reading • R Qureshi,(2015) Introduction to Transfusion Science Practice, BBTS. Chapter 6, ABO blood group system, p122 - 140. • Overfield et.al. Transfusion Science, Scion Chapter 5, Introduction to the blood groups: the ABO system . • Daniels G. Human Blood Groups, Blackwell Science, Oxford. • Eva D Quinly Immunohematology Principles and Practice, Lippincott-Raven, Pennsylvania
Complete the following Punnet charts for ABO inheritance. Parents group AB and O
Parents group AB and AB
Parents group A and O
Parents group A and AB
Overview.
• Genetics • Inheritance. • ABO,Hh,Sese locus.
• Antigens. • Antibodies.
• Clinical Significance. • Subgroups A1 and A2. • Geographic distribution.
ABO Blood Groups. • 1900 Austria Karl Landsteiner • Mendelian inheritance of A, B or O gene. • One from each parent. • A and B genes co-dominant. • O gene amorphic. http://www.nobelprize.org/nobel_prizes/medicine/laureates/1930/landsteiner-bio.html
Phenotype
Genotype
O
OO
A
AA, AO
B
BB, BO
AB
AB
ABO Inheritance. Parents group A and B A A B AB AB B AB BB
A O B AB BO O AO OO
Parents group A and A A A A AA AA A AA AA
A O A AA AO A AA AO
A B AB B AB
O BO BO
A O A AA AO O AO OO
Gene Action Three Loci: FUT1, FUT2, ABO
Genes code for production of specific glycosyltransferases Enzymes transfer immunodominant sugars from donor molecules to preformed oligosaccharide chain thus changing the antigen specificity.
ABO locus • ISBT No: 001. • Symbol: ABO. • Gene name: ABO. • Chromosome: 9 • Gene products: • n-acetyl galactosaminyltransferase. • D-galactosyltransferase • Converts H to A, B antigen. • Sugar donor: UDP.
FUT1 (Hh) locus • ISBT No: 018. • Symbol: H. • Gene name: FUT1. • Chromosome: 19 • H dominant, h amorph. • Gene product: fucosyltransferase. • Converts basic precurso substance to H antigen. • Sugar donor: GDP.
FUT2 (Sese) locus Chromosome 19
•"Secretors" (SeSe or Sese) secrete type 1 precursor substance. •Se dominant, se amorphic. •Encodes a fucosyltransferase expressed in epithelia of secretory tissues. •Production of H antigen in secretions.
Type II Red Cell Surface D-galactose N-acetylglucosamine N-acetyl-D-galactosamine
L-fucose
β-1,4
Type I
β-1,3
Precursor substance
H Antigen L-fucosyltransferase Type I
Type II Red Cell Surface D-galactose N-acetylglucosamine N-acetyl-D-galactosamine
L-fucose
A Antigen N-acetyl galactosaminyltransferase
Red Cell Surface D-galactose N-acetylglucosamine N-acetyl-D-galactosamine
L-fucose
B Antigen
D-galactosyltransferase
Red Cell Surface D-galactose N-acetylglucosamine N-acetyl-D-galactosamine
L-fucose
ABH null phenotype Oh H H h
H H H
H h H
H H h
H h H
Phenotype Genotype
h h h
Genotype Phenotype
No H – no ABO antigens Anti-H, anti-A, anti-B and anti-A,B in serum Transfuse only with blood from Oh donor. 1952, Bhende YM et al
Antibodies Produced 4-6 months after birth.
IgM -“naturally IgG -
occurring” Activate complement and cause severe HTR.
Immune anti-A,B in group O
Can cross placenta and cause mild to moderate Haemolytic Disease of the Foetus and Newborn.
Group O serum anti-A,B. • Higher IgG component. • High titre group O donors.
• antibody reacts clearly at a 1:10 dilution. • not used for plasma products.
• Not simple mixture of anti-A and anti-B.
Group O serum Absorption and elution studies
u
u
Eluate + group A cells
Elution Anti-A,B + group B cells.
Inhibition studies.
Eluate.
Eluate + group B cells
Saliva from group A or B secretors inhibits reaction of anti-A,B with A or B cells.
Transfusion practice
ABO group A
Antibodies in plasma Anti-B
Compatible donor ABO blood group A, O and Oh
B
Anti-A
B, O and Oh
AB
None
AB, B, O and Oh
O
Anti-A, anti-B, O and Oh (anti-A,B) Oh Anti-A, anti-B, Oh only (anti-A,B), anti-H Donor blood must be crossmatched before transfusion.
Subgroups A1 and A2 80% of group A individuals are A1, 20% A2 Anti-A1 Anti-A Anti-H
A1 cells 4 4 1
A2 cells 0 2-3 3
Quantitative difference A1
8-12 X 105 A antigens
A2
1-4 X 10
5
,,
A1 and A2 Qualitative difference • 2% of A2 have anti-A1 as well as anti-B; • 25% of A2B have anti-A1
• NB. Anti-A2 does not exist!
Amount of H antigen in ABO blood groups O>A2>B>A2B>A1>A1B
Geographical distribution
Frequencies-(A and A ) 1
2
Summary.
• Mendelian Inheritance.
• A & B co-dominant, O amorph. • Three loci involved ABO,Hh,Sese. • Carbohydrate antigens • Glycosyltransferases • Antibodies mostly complement activating IgM + low level IgG. Group O serum. • Acute HTRs and mild HDFN. • Subgroups A1 and A2 differences. • Geographic distribution.
Further reading • R Qureshi,(2015) Introduction to Transfusion Science Practice, BBTS. Chapter 6, ABO blood group system, p122 - 140. • Overfield et.al. Transfusion Science, Scion Chapter 5, Introduction to the blood groups: the ABO system . • Daniels G. Human Blood Groups, Blackwell Science, Oxford. • Eva D Quinly Immunohematology Principles and Practice, Lippincott-Raven, Pennsylvania
Complete the following Punnet charts for ABO inheritance. Parents group AB and O
Parents group AB and AB
Parents group A and O
Parents group A and AB
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