The Duffy (008) System

 Discovered in 1950
 Named after Mr. Duffy
o Haemophiliac
o Multiple transfusion patient
o First known producer of anti-Fya
 1951
o anti-Fyb was discovered from a woman who had 3 pregnancies
 20 years after
o Fy3, Fy4, Fy5, Fy6 was discovered
o Fy3 is the only significant

Added info:
 Fy3 & Fy5 Ab are rarely encountered
 Fy5
o not present in Rhnull RBCs

I. Frequency of Duffy (008) phenotype

 Fy (a – b –) = Duffy null phenotype
o Rare in Caucasians and Asians
o Most common in African- Americans
o Gene responsible: Fy
o In vitro, resists infection by Plasmodium knowlesi
o Resists infection by Plasmodium vivax

II. Nomenclature of Duffy (008) system

 Number of Duffy antigens: 6
 ISBT symbol: FY
 ISBT number: 008
 Gene symbol: FY
 Gene name: Duffy blood group

III. Fya and Fyb Ag

- Most important Duffy Ag in routine blood banking serology
- Seen as early as 6 weeks of gestational age
- Well-developed thereafter
- Expressed in different cells

Note! People with Fy (a – b –) still express Fya and Fyb Ag

 ((those who do not produce duffy Ag on RBC))
Found on the:
1. Brain 3. Endothelium
2. Colon 4. Lung
 5. Spleen 7. Thymus
6. Thyroid 8. kidney cells
BUT NOT on:
1. Monocytes 3. Lymphocytes
2. Granulocytes 4. Platelets

- Destroyed by proteolytic enzyme

 Or proteases
1. Ficin
2. Papain
3. Bromelin
4. Chymotrypsin
5. ZZAP
 Dithiothreitol + Papain

IV. Anti- Fya & Anti- Fyb

a. Anti- Fya
- Common Ab
- Found in a single specificity or in a mixture of Ab

b. Anti-Fyb
- 20x less common than anti-Fya
- Found in combination with other Ab
 What Ab? IgG!!
 React best @ AHG phase

- Low Ionic strength medium = where the Ab activities are enhanced

- Anti- Fya & Anti- Fyb = DO NOT react w/ enzyme- treated RBCs
 Helpful when present ang ibang Ab
- Some examples of Anti-Fya & Anti-Fyb show dosage
o Reacts more strongly with RBCs that have double dose
 Importance na they show dosage? Kasi some homozygotes are actually heterozygotes
lalo na if from African-Americans.
NOTE!
 African- Americans have Fy allele
 Silent allele
 Ex. Fy(a+ b-)
 Double dose of Fya  FyaFya donor: White person
 Single dose of Fya  FyaFy donor: Black person

- Diseases associated
 a. Acute & delayed haemolytic transfusion reactions
b. Hemolytic disease of the newborn

V. Genetics
a. Duffy gene
- Linked to Chromosome 1 abnormality
 1st human gene to be assigned to specific chromosome
- Located near the centromere of the long arm of chromosome 1
b. Fy gene
- Locus is syntenic to the Rh locus
- Location: near the tip of the short arm
 Pero far enough to differentiate them serologically
- Has 3 common alleles
1. Fya = encode the antithetical antigen Fya
2. Fyb = encode the antithetical antigen Fyb
3. Fy = silent allele; major allele in African- Americans
= @ African- Americans: Fyb variant w/ a change in promoter region
 Importance? Disrupts the mRNA transcription binding site @RBC
Note!
 Fy (a – b –) = no Fyb @ RBCs; but, seen in other tissues
 Importance? Para hindi masabi ng katawan na foreign siya
 Else, gagawa katawan natin ng antibody against it

 Fy (a – b –) in white people
 Different naman mutation nila
- Has NO DUFFY protein on neither of their RBC nor other tissues
- Has anti-Fyb & anti-Fy3

 Duffy Ag typing is done on RBCs of

o Chimpanzees
o Gorillas
o Old & New World monkeys
 Fy3 una, Fyb, then Fya
= OTHER ANTIGENS=
VI. Fyx
- Described as a new allele at the Fy locus seen in white people
- Does not produce a distinct antigen
- An inherited weak form of Fyb
 Reacts with some anti-Fyb – adsorb & removes them
- Have depressed expression of Fy3 & Fy5 Ags
- ↓ Fy b when ↑ Fyx due to ↓ Duffy glycoprotein @ RBC

Note!
There is no anti- Fyx !
VII. Fy3
- Anti - Fy3 was discovered in serum of Fy(a – b – ) white Australian
- Did not react with those of the Fy(a – b –) phenotype
- Coined as Fy3 because it was thought that they react w/ antigenic determinant
common to Fya & Fyb
- Not destroyed by enzymes

 Anti – Fy3
- Rare antibody
- Made by Fy(a – b –) individuals
- Reacts with all Fy(a+) or Fy(b+) RBCs but not with Fy(a – b –)
 Lacking Duffy glycoprotein

VIII. Fy5
- Molecular structure is not known
- Result of interaction b/w the Rh complex and Duffy glycoprotein
- People who are Rhnull & Fy(a – b –) do not make Fy5 Ag
- At risk of making anti- Fy5
- Not destroyed by enzymes

 Anti – Fy5
- Discovered by College & coworkers
 In serum of Fy(a – b –) black child who died of leukemia
- Thought to be 2nd example of anti – Fy3
 Pero hindi kasi it doesn’t react w/ Fy (a+) & Fy(b+) Rhnull
 Weak rxn w/ fya+ fyb+ D – RBCs

The Kidd (009) system

I. Introduction
- Consists of only 3 antigens
- Discovered by Allen & colleagues
o Found an Ab in serum of Mrs. Kidd targeted against unknown Ag during her
pregnancy
 Marker was on RBC of fetus, so syempre yung Ab targeted yon causing HDN
o Named the Ab = anti-Jka
 anti-Jka
o reacted w/ 77% of Bostonians
o Jkb = antithetical partner of anti-Jka
 Found 2 yrs after anti-jka

 Jk (a – b –)
o Null phenotype in Kidd system
o Described in 1959
 Found in mommy na nagka-jaundice after blood transfusion
 May nakitang Ab that recognizes Jka & Jkb = anti- JK3

 Jk3
o A high-prevalence Ag
o Present when Jka and Jkb are present

II. Nomenclature of Kidd (009) system

 Number of Kidd antigens: 3
 ISBT symbol: JK
 ISBT number: 009
 Gene symbol: SLC14A1
 Solute carrier family 14, member 1
 Gene name: Kidd blood group

 Significant kasi its Abs are difficult to detect & common cause of HTRs

III. Jka and Jkb antigens

- Commonly found on RBCs of most individuals

Frequency Antigen
91% black Jk (a+)
77% white
57% black Jk (b-)
28% white
- Well developed in neonates
o 11 weeks gestational age = Jka
o 7 weeks of gestational age = Jkb
- Early development contributes to potential HDFN
- Not very immunogenic
 - NOT denatured by enzymes – papain or ficin
- Enzymes enhances reactivity
- NOT affected by Chloroquine, DTT, AET, Glycine- acid EDTA

NOT found:
1. Monocytes 3. Lymphocytes
2. Granulocytes 4. Platelets
IV. Anti- Jka and ant-Jkb
- Demonstrates dosage
- Weak
- Found in combination w/ other Ab
 Difficult to detect
- Reacts more strongly wi/ RBC that has double dose of respective Ag
- May not react w/ Jk3

 Anti- Jka
- More frequently encountered than Anti- Jkb
- Neither Ab is common
o Usually IgG but can be IgM
 IgG – antiglobulin reactive
 IgM – in response to pregnancy & transfusion

 Antibody reactivity
a. LISS or PEG
- enhances antibody reactivity
- promotes IgG attachment
- use: 4 drops of serum // ficin or papain
 to INC. Ab-Ag ratio

 Anti- Jka and ant-Jkb titer

- Quickly declines in vivo
 Mataas after a transfusion reaction UNDETECTABLE after a week or month
↓ Ab reactivity & Difficulty in detecting Kidd Ab
 Common cause of HTRs

V. Genetics
- Jk locus found on chromosome 18
- Member of the urea transporter gene family
- Gene is organized into 11 exons
- Jka /Jkb polymorphism
o Amino acid substitution @ position 280
- Silent Jk allele
o Jka & Jkb mutation
 VI. Jk(a – b –) phenotype
- Lack Jka, Jkb, and Jk3
- Very rare
- Though, most abundant in Polynesians
o Filipinos
o Indonesians
o Chinese
o Japanese
- Found also in several Europeans & Mato Grosso Indians of Brazil
- How to detect?
o Its delayed lysis property in 2M urea
- No clinical abnormality

VII. Anti- Jk3

- Utilizes antigen typing to determine its most probable specificity
- Reacts optimally by antiglobulin test
- Reactivity is enhanced with enzymes
- Assoc w/ severe immediate & delated HTRs & mild HDFN

Lutheran (005) system

I.
- Named after the donor for the patient suffering from Lupus erythematosus
o Though it was incorrectly labelled
o Ptx with Lupus erythematosus had an anti- Lua Ab
- Cutbush & Chanarin
o Described the anti-Lub
 Antithetical partner of Lua
- Crawford & colleagues
o Described the Lu (a – b –) phenotype
o Demonstrated dominant inheritance
- 1963
o Described the recessive silent Lu (a – b –) phenotype

II. Nomenclature of Lutheran (005) system

 Number of Lutheran antigens: 20
 ISBT symbol: Lu
 ISBT number: 005
o Lu10 & Lu15 = obsolete
 Numbered through Lu22