MIDTERM LECTURE L1: DUFFY BLOOD GROUP Flashcards
ISBT # of Duffy blood group
ISBT #008
When was anti-Fya first identified
1950 from Mr. Duffy, a multiply transfused hemophiliac
when and where was anti-Fyb first found
1951, found in the serum of a woman who had three pregnancies
Who reported that the majority of African Americans tested were Fy (a-b-)
Sanger and colleagues
Gene responsible for the null phenotype
Fy
Most common grnotypenin blacks, especially in Africa
FyFy
What Duffy rbc phenotype resist infection in vitro by Plasmodium knowlesi
Fy (a-b-)
Fy (a-b-) phenotype resist infection of what organisms
Plasmodium kowlesi
Plasmodium vivax
T or F:
Fy (a-b-) rbcs are also Fy: -3, -5
T
T or F: Fy5 can be expressed in Rh null RBCs
F (regardless of the Fya or Fyb status of those rbcs
Symbol of the Duffy blood group system
FY
Most important Duffy antigens
Fya and Fyb
When can Fya and Fyb be identified on fetal rbcs
6 weeks
T or F: Fya and Fyb are well developed at birth
T
How many Fya and Fyb sites are on Fy (a+b-) and Fy (a-b+) RBCs
13,000-14,000
How many Fya sites are on Fy (a+b+) RBCs
Half of 13,000-14,000
Fya and Fyb antigens cannot be found on what cells
Platelets
Lymphocytes
Monocytes
Granulocytes
Fya and Fyb antigens have been identified in what body tissues
Brain
Colon
Endothelium
Lung
Spleen
Thyroid
Thymus
Kidney cells
T or F: Fya and Fyb antigens are destroyed by common proteolytic enzymes
T
What common proteolytic enzymes can destroy Fya and Fyb
Ficin
Papain
Bromelin
Chymotrypsin
ZZAP
ZZAP is a combination of what reagents
Papain or ficin w/ dithiothreitol
What proteolytic enzymes cannot alone destroy Fya and Fyb
DTT (dithiothreitol)
AET
Glycine-acid EDTA treatment
What enzyme may reduce the molecular weight of Fya and Fyb but does not destroy antigenic activity
Neuraminidase
Purified trypsin
Common antibody and is found as a single specificity or in a mixture of antibodies
Anti-Fya
Anti-Fya occurs three times less frequently than what antibody
Anti-K
How common is anti-Fyb
20 times less than anti-Fya
This antigen often occurs in combination with other antibodies
Anti-Fya
Duffy antibodies are usually what class
IgG
Duffy antibodies react best at what phase
Antiglobulin phase
T or F: rare examples of Fya and Fyb can bind complement
T (saline agglutinins)
Antibody activity is enhanced in what medium
Low-ionic strength medium
T or F: anti Fya and anti-Fyb react with enzyme treated RBCs
F
T or F: anti-Fya and anti-Fyb can show dosage effect
T
What is dosage effect
Phenomenon where antibodies react more strongly with double dose (homozygotes) than single dose (heterozygotes)
Double dose of either Fya and Fyb may be heterozygotes if it is from what donor ethnicity
Blacks
Silent allele Fy is commonly found in what ethnicity
Blacks
Anti-Fya and anti-Fyb have been associated with was complications
Acute and delayed HTR
Mild to severe HDFN
Once anti-fya and anti-fyb is identified, what blood must be given
Fy (a-) or Fy (b-)
What is a characteristic of rare autoantibodies mimicking Fya and Fyb specificity?
They can sometimes be adsorbed onto and eluted from Fy(a+b–) RBCs.
Who suggested that rare autoantibodies with Fya and Fyb specificity may be alloantibodies with “sloppy” specificity formed early in an immune response?
Issitt and Anstee
What does it mean when an anti-Fyb autoantibody can be adsorbed onto and eluted from Fy(a+b–) RBCs?
It suggests that the antibody may have broader or less specific binding characteristics.
According to Issitt and Anstee, when might alloantibodies with “sloppy” specificity form?
Early in an immune response
what methods have been used to study the biochemistry of Duffy antigens
1) enzymes
2) membrane solubilization
3) immunoblotting
4) radiolabeling
5) amino acid sequencing
How many amino acids make up the glycoprotein that carries Duffy antigens?
336 amino acids
What is the relative mass of the glycoprotein carrying Duffy antigens?
36 kD
How many N-glycosylation sites are present on the Duffy antigen glycoprotein?
two
What amino acid at position 42 defines the Fya and Fyb polymorphism?
Glycine for Fya and aspartic acid for Fyb.
Which amino acid region is involved in the Fy6 epitope?
Amino acids 19 through 25.
What is another name for the Duffy glycoprotein based on its function?
Atypical chemokine receptor 1 (ACKR1), previously known as DARC.
Besides being a receptor for Plasmodium vivax, what else does the Duffy glycoprotein bind?
proinflammatory cytokines
What chromosome is the Duffy gene (ACKR1) associated with?
chromosome 1
What was the former name of the Duffy gene ACKR1?
DARC (Duffy Antigen Receptor for Chemokines)
ACKR1 gene position in chromosome 1
long arm, 1q21-q22
Fy locus us syntenic to which blood group locus
Rh locus
three common alleles at the Fy locus
Fya, Fyb, and Fy
what antigens does Fy encode
none, silent allele
Fy is a major allele in what ethnicity
blacks
What is the predominant Fy gene variant in Fy(a–b–) Black individuals?
Fyb
What specific change occurs in the promoter region of the Fy gene in Fy(a–b–) Black individuals?
GATA gene mutation
How does the GATA mutation affect the Fy gene in RBCs?
disrupts the binding site for mRNA transcription, preventing expression in RBCs
T or F:
Fy(a-b-) black express anti-Fyb
F
(Fyb is not foreign, still express in tissues)
Molecular testing for the GATA
mutation is helpful for transfusion management for patients
with what disease
sickle cell disease
Fy(a-b-) whites produce what antibodies
anti-Fyb and anti-Fy3
Fy gene that is an inherited weak form of Fyb that reacts with some examples of anti-Fyb
Fyx
what antigen does Fyx gene produce
no distinct antigen
T or F:
there is anti-Fyx
F
phenotype of individuals with Fyx gene may be
Fy(b-)
Fyx may cause depressed expression of what antigens
Fy3 and Fy5
in 1971, anti-Fy3 was found in the serum of what individual
Fy(a-b-) white Australian female
what antibody reacts with both Fya and Fyb but cannot be separated?
anti-Fy3
How does anti-Fy3 differ from anti-Fya and anti-Fyb?
Anti-Fy3 reacts with all Fy(a+) and Fy(b+) RBCs, while anti-Fya and anti-Fyb only react with their respective antigens.
T or F:
Fy3 antigen can be destroyed by enzymes
F
what phenotype makes anti-Fy3
Fy(a-b-) especially whites
T or F:
all Fy(a–b–) Black individuals make anti-Fy3?
F
they rarely make anti-Fy3 because they still express the Duffy glycoprotein in non-RBC tissues.
Which Duffy antibody do some Fy(a–b–) Black individuals produce before anti-Fy3?
anti-Fya
who discovered anti-Fy5
Colledge and coworkers in 1973
where did Colledge anti-Fy5
serum of an Fy(a-b-) black child who died of leukemia
How does anti-Fy5 differ from anti-Fy3?
Anti-Fy5 reacts with Fy(a–b–) white RBCs
but not Fy(a–b–) Black RBCs and does not react with Rhnull RBCs
T or F:
Fy5 can be destroyed by enzymes
F
who can make anti-Fy5
Fy(a–b–) or Rhnull individuals exposed to Fy5-positive blood
antibody made by Duffy null phenotype
anti-Fy3
T or F:
Fya and Fyb antigens do not store well in saline suspension
T
T or F:
Fya and Fyb antigens are destroyed in enzyme treatment
T
