Beruflich Dokumente
Kultur Dokumente
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 A O A O
B AB AB B AB BO B AB BO
B AB BB O AO OO B AB BO
Parents group A and A
A A A O A O
A AA AA A AA AO A AA AO
A AA AA 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.
Precursor substance
-1,3
Type I
-1,4
Type II
D-galactose
N-acetylglucosamine
N-acetyl-D-galactosamine
L-fucose
H Antigen
L-fucosyltransferase
Type I
Type II
D-galactose
N-acetylglucosamine
N-acetyl-D-galactosamine
L-fucose
A Antigen
N-acetyl galactosaminyltransferase
D-galactose
N-acetylglucosamine
N-acetyl-D-galactosamine
L-fucose
B Antigen
D-galactosyltransferase
D-galactose
N-acetylglucosamine
N-acetyl-D-galactosamine
L-fucose
ABH null phenotype Oh
H H Phenotype
H h H h Genotype
H H H h H h h h Genotype
H H H h 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.
u
Eluate +
u group A cells
Elution
Anti-A,B + Eluate.
group B cells. Eluate +
group B cells
Inhibition studies.
Saliva from group A or B secretors inhibits
reaction of anti-A,B with A or B cells.
Transfusion practice
ABO Antibodies in Compatible donor
group plasma ABO blood group
A Anti-B 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
A1 cells A2 cells
Anti-A1 4 0
Anti-A 4 2-3
Anti-H 1 3
Quantitative difference
A1 8-12 X 105 A antigens
A2 1-4 X 10 5
,,
A1 and A2
Qualitative difference
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 Parents group Parents group
AB and O AB and AB A and AB
Parents group A and O