MIDTERM LEC: Other Major Blood Group System Flashcards
Both antigens are expressed
CODOMINANT
Most blood group alleles are codominant and express a corresponding antigen
CODOMINANT
“Silent alleles”
AMORPHIC
alleles exist that make no antigen, but they are rare
AMORPHIC
When paired chromosomes carry the same silent allele, it results to a null phenotype
AMORPHIC
Cannot be expressed
AMORPHIC
Only determines the phenotype only
SEROLOGIC TESTING
actual gene of an individual; the genetic makeup
Genotype
ISBT #007
LEWIS BLOOD GROUP SYSTEM
MAJOR BLOOD GROUPS:
● LEWIS
● KELL
● KIDD
● DUFFY
● LUTHERAN
Not intrinsic to Red Blood Cell
LEWIS BLOOD GROUP SYSTEM
Not intrinsic to Red Blood Cell meaning?
Antigens are not produced by RBCs, it is being adsorb into the RBCs
Manufactured by tissue cells and secreted into body fluids (adsorbed into RBCs)
LEWIS BLOOD GROUP SYSTEM
LEWIS BLOOD GROUP SYSTEM
Le GENE Located at:
Chromosome 19p13.3
LEWIS BLOOD GROUP SYSTEM
Se GENE Located at:
Chromosome 19q
Production depends not only on the inheritance of Le genes but also on the inheritance of Se gene
LEWIS BLOOD GROUP SYSTEM
LEWIS BLOOD GROUP SYSTEM
2 Major Antigens:
Lea and Leb
Expression of these antigens would have an effect on the presence of the gene that will encode for the enzyme for a certain carbohydrate to attach
Lea and Leb
Lewis antigen
Lea
*
Se antigen
Leb
LEWIS BLOOD GROUP SYSTEM
Antigens secreted and absorbed onto: [RLP]
○ RBC
○ Lymphocytes
○ Platelet membrane from plasma
Somewhat related to the ABO blood group because of the sugars attached on the RBC membrane
LEWIS BLOOD GROUP SYSTEM
Codes for fucosyltransferase-3 (FUT3) so that fucose molecules will attach to the N-acetyl-D-galactosamine (GalNac) = Lea
Le GENE
Has genes that will produce the enzymes and therefore producing a
specific sugars
LEWIS BLOOD GROUP SYSTEM
Codes for the secretory enzyme, fucosyltransferase-2 (FUT2) so that 1 fucose molecule will attach to the galactose = Leb
Se GENE
80% of the individuals have this gene
Se GENE
Stronger in terms of expression compared to Le Gene
Se GENE
THE LEWIS PHENOTYPE:
Le (a+b-)
Le (a-b+)
Le (a-b-)
Both of the genes can be present
Le GENE
Se GENE
LE1 - 007.001
Le (a+b-)
Nonsecretor
Le (a+b-)
Secretor
Le (a-b+)
LE2 - 007.002
Le (a-b+)
Secretor or Nonsecretors
Le (a-b-)
Lea
■ Present in plasma:
glycolipids
Leb
■ Secretions
glycoprotein (20% carbohydrates and 15% amino acid)
_____ molecules are attached on type 1 chain
Fucose
Le2(a-b-) from plasma can be converted to Le(a+b-)/Le(a-b+)
T OR F
T
- Lewis antigen is present in saliva but absent in the plasma
○ All newborns started as Le(a-b-)
Newborns
Le(a-b-) → Le(a+b-) → Le(a+b+) → Le(a-b+)
Inherited Le and Se genes will develop overtime
○ Le(a-b-) → Le(a+b-)
○ persists throughout life
If the Inherited Le and Sese gene
If inherit lele gene:
○ Le(a-b-)
○ birth and for the rest of their life
CHANGES IN LEWIS PHENOTYPE:
● Phenotype changes
● Can vary all throughout life
● Not capable of causing:
CHANGES IN LEWIS PHENOTYPE
● Not capable of causing:
- Hemolytic Disease of the Fetus and Newborn (HDFN)
- Hemolytic Transfusion Reaction (HTR)
- Changes in Lewis phenotype can be seen in the following
Even if the mother has IgG antibodies that passes the placenta, there will be no reaction that will happen since fetuses start as Le(a-b-)
Hemolytic Disease of the Fetus and Newborn (HDFN)
■ RBCs change rapidly from donor to recipient
■ Example: Lewis antigen of the donor is different from the recipient. Even though the recipient receives the blood from the donor, there will be no reaction that will happen. The recipient’s RBCs will just adsorb whatever is present in the donor’s Lewis blood type
Hemolytic Transfusion Reaction (HTR)
Changes in Lewis phenotype can be seen in the following: [PCAVG]
○ Pregnancy women: Le (a-b-)
○ Cancer
○ Alcoholic Cirrhosis
○ Viral and Parasitic Infection
○ Genetic Reasons
■ Pregnant women has higher plasma content
that will make the secretor status lower in numbers. (Similar to dilution effect)
■ Little secretor antigen will be adsorb by the pregnant women’s RBCs
Pregnancy women: Le (a-b-)
IgM, naturally occurring
LEWIS ANTIBODIES
Frequent in pregnant women (serum)
LEWIS ANTIBODIES
May occur together
LEWIS ANTIBODIES
*
More reactive with O cells
LEWIS ANTIBODIES
Anti-Lea
do not make anti-Lea (anti-Lea structure is contained within Leb structure)
Le(a-b+)
LEWIS ANTIBODIES
Anti-Lea & Anti-Leb
Detected with saline-suspended cells at RT (agglutinates are often fragile and can be easily dispersed if the cell button is not gently resuspended after centrifugation)
Anti-Lea
Neutralized with plasma or saliva
Anti-Lea
Either IgG or IgM, but usually IgM
Anti-Lea
Anti-Lea
anti-Lea is commonly seen
Le(a-b-)
IgM
Anti-Leb
Most common
Anti-Leb
Produced by Le(a-b-)
Anti-Leb
Neutralized by plasma or saliva
Anti-Leb
*
Has 2 categories
Anti-Leb
Anti-Leb
Has 2 categories:
- anti-Lebh
- anti-Lebl
reacts best when both the Leb and the H antigens are present on the RBC, such as group O and A2 cells. (H dependent)
anti-Lebh
recognizes any Leb antigen regardless of the ABO type (H independent)
anti-Lebl
Formed by Le(a-b-)
Anti-Lex
Agglutinates 90%
Anti-Lex
Can be neutralized by the Lewis substances present in the plasma
CLINICAL SIGNIFICANCE (Ab
Dissociates from the RBCs as readily as they bind to RBC
CLINICAL SIGNIFICANCE (Ab
*
Generally IgM
CLINICAL SIGNIFICANCE (Ab
ISBT #002
MNS BLOOD GROUP SYSTEM
attached to glycoproteins, which is an important part of a cell membrane
M & N ANTIGEN
Found in glycophorin A
M & N ANTIGEN
Rich in sialic acid (sialoglycoprotein) coded by Glycophorin A (GPA)
M & N ANTIGEN
Well developed at birth
M & N ANTIGEN
M and N differ in amino acid residues at
positions 1 and 5
M =
Serine and Glycine
N =
Leucine and Glutamic Acid
Detected on renal endothelium, and epithelium
MNS BLOOD GROUP SYSTEM
Destroyed by enzyme treatment and ZZAP+ DTT + papain/ficin
MNS BLOOD GROUP SYSTEM
Both are codominant
MNS BLOOD GROUP SYSTEM
Found in glycophorin B
S & s ANTIGEN
Well developed at birth
S & s ANTIGEN
Destroyed by enzyme treatment (Ficin, Papain, Bromelin, Pronase & Chymotrypsin)
S & s ANTIGEN
S and s differ in amino acid at
position 29
S =
methionine
s =
threonine
MNS ANTIBODIES
- Anti-M
- Anti-N
- Anti-S & Anti-s
Naturally occurring
Anti-M
50-80% IgG
Anti-M
Do not bind complement
Anti-M
Do not react w/ enzyme treated RBCs
Anti-M
Common in children and patient with burns
Anti-M
pH dependent (pH 6.5)
Anti-M
Detected in plasma
Anti-M
Lectin: Iberis amara
Anti-M
Not a significant cause of HDFN
Anti-M
Cold reactive, IgM or IgG
Anti-N
Dosage effect
Anti-N
Not clinically significant
Anti-N
Does not bind complement
Anti-N
Seen in renal patients (Formaldehyde may alter the M and N antigens)
Anti-N
Anti-N
Lectins:
● Vicia graminea
● Bauhinia variegate
● Bauhinia purpura
Mostly IgG
Anti-S & Anti-s
Reactive at 37C
Anti-S & Anti-s
Dosage effect
Anti-S & Anti-s
Can bind complement
Anti-S & Anti-s
Implicated in severe HTR and HDN
Anti-S & Anti-s
ISBT #003
P BLOOD GROUP SYSTEM
Can be detected 12 weeks in fetal RBC
P1 ANTIGEN
7 years old: fully expressed
P1 ANTIGEN
Gestational age: weaken
P1 ANTIGEN
Strength can vary on quantity and race
P1 ANTIGEN
Deteriorates rapidly on storage → false negative (freshly prepared)
P1 ANTIGEN
naturally occurring, IgM
ANTI-P1 ANTIBODY
weak, cold reactive saline agglutinin
ANTI-P1 ANTIBODY
ANTI-P1 ANTIBODY
Enhance Reaction by: [FIP]
● Fresh RBC preparation
● Incubate cells at RT or lower
● Preheating cells with enzymes
ANTI-P1 ANTIBODY
neutralized by hydatid cyst fluid from: [EPT]
● Echinococcus granulosus infection
● Pigeon dropping
● Turtle dove egg white
SOURCES OF P1 ANTIGEN AND ANTIBODY:
Echinococcus granulosus
SOURCES OF P1 ANTIGEN: [PRED]
■ Plasma
■ RBCs
■ Egg white of turtle doves
■ Droppings of pigeons and turtle doves
SOURCES OF P₁ Antibody: [COAL]
■ Clonorchis sinensis
■ Opisthorchis viverrini
■ Ascaris suum
■ Lumbricoides terrestris
T in the Tja refers to tumor
Anti-PP1 Pk (Anti-Tja)
scovered in serum of patient “Mrs. Jay” with adenocarcinoma of stomach
Anti-PP1 Pk (Anti-Tja)
Produced by p individual
Anti-PP1 Pk (Anti-Tja)
IgM and IgG
Anti-PP1 Pk (Anti-Tja)
Associated with PCH (Paroxysmal Cold Hemoglobinuria)
Autoanti-P
associated with increased incidence of spontaneous abortions in early pregnancy
Anti-PP1 Pk (Anti-Tja)
IgG antibody
Autoanti-P
Cold reactive
Autoanti-P
Detects biphasic hemolysin
Donath-Landsteiner Test
Biphasic hemolysin: binds to RBCs at low temperature and activates complement to produce in-vitro hemolysis at warmer
temperatures
Donath-Landsteiner Test
Can be detected 12 weeks in fetal RBC
Donath-Landsteiner Test
binds to RBCs at low temperature and activates complement to produce in-vitro hemolysis at warmer temperatures
Biphasic hemolysin
P BLOOD GROUP SYSTEM
DISEASE ASSOCIATION:
○ Parasitic infection
○ Early abortion
○ PCH
○ Urinary Tract Infection
○ Septicemia and meningitis
○ P antigens
P antigens:
■ Pyelonephritogenic E. coli
■ Streptococcus suis
■ Shigella dysenteriae
ISBT #027
I BLOOD GROUP SYSTEM
1956 - Wiener and coworkers; I for “individuality.”
I ANTIGEN
I
undetectable
I = adults; i= infants
I ANTIGEN
i
slowly decreases (first 18 months)
adult RBCs are rich in I and have only trace amounts of i antigen
T OR F
T
I BLOOD GROUP SYSTEM
neutralized by
Human Milk
○ “I” activity is increased in individuals with Bombay phenotype and if ABH sugars are removed by enzymes
○ Adult “i”
I BLOOD GROUP SYSTEM
I BLOOD GROUP SYSTEM
Sources:
membrane of leukocytes and platelets
IgM
Anti-l
Strong agglutination: Adult
Anti-l
Weak agglutination: Cord RBCs
Anti-l
*
Detectable at 4C
Anti-l
Can be found in serum
Anti-l
Strong Reaction: Cord RBCs, Adult “i”
Anti-i
IgM, detectable at 4C
Anti-i
Anti-i
Associated with: [IRAM]
■ Infectious Mononucleosis (Epstein barr Virus)
■ Reticuloses
■ Alcoholic cirrhosis
■ Myeloid leukemia
It Antigen and Antibody
1965:
Curtain and coworkers reported a cold agglutinin in Melanesians that did not demonstrate classical I or i specificity
It Antigen and Antibody
1966:
Booth and colleagues confirmed these observations
It (T for “transition”)
It Antigen and Antibody
It Antigen and Antibody
Reaction:
■ Strong: Cord RBC
■ Weak: Normal adult RBC
■ Most Weak: Adult “i”
○ IgM
○ Associated with organism or parasite
It Antigen and Antibody
ISBT #027
KELL BLOOD GROUP SYSTEM
Warm reactive, IgG, reactive in AHG phase, involved in HDN and HTR
○ IgG1: cannot fix complemen
KELL BLOOD GROUP SYSTEM
Originated from Mrs. Kellaher, from whom anti-K was first identified
○ Baby of Mrs. Kellaher has anemia
○ Mrs. Kellaher tested negative in her DAT test. They found out that it does not make agglutination
○ Antigen + Antibody = coats the RBC = extravascular
hemolysis
KELL BLOOD GROUP SYSTEM
Detection: 10 weeks at fetal RBC (k: 7 weeks)
KELL BLOOD GROUP SYSTEM
Most immunogenic second to D
KELL BLOOD GROUP SYSTEM
KEL gene at chromosome 7
KELL BLOOD GROUP SYSTEM
*
Resistant proteolytic enzymes
KELL BLOOD GROUP SYSTEM
RBCs are acanthocytic
KELL BLOOD GROUP SYSTEM
X-linked, occurs when Kx antigen is not expressed
McLeod Phenotype
ISBT #008
DUFFY BLOOD GROUP SYSTEM
NADH-oxidase is deficient in WBCs
McLeod Phenotype
*
Associated with Chronic Granulomatous Disease (CGD)
McLeod Phenotype
1950: named for Mr. Duffy, a multiply transfused hemophiliac
DUFFY BLOOD GROUP SYSTEM
RBC lack Kx and Km and other Kell antigens are depressed K-negative when transfused with Kpositive will create anti K as high as 10% chance
McLeod Phenotype
Has receptors IL-8 for inflammation
Duffy Antigen Receptor Cytokines (DARC) gene
Has receptors for Plasmodium knowlesi & Plasmodium vivax
Duffy Antigen Receptor Cytokines (DARC) gene
associated with African-American Population (1955 - Sanger & colleagues)
Fy(a-b-) phenotype
Confers resistance to Plasmodium vivax infections
Fy(a-b-) phenotype
do not store well in saline suspension
Fya and Fyb antigens
destroyed in enzyme treatment
Fya and Fyb antigens
usually warm reacting, reacts at AHG phase (IgG)
Anti-Fya and Anti-Fyb
antibody made by Duffy Null phenotype
Anti-Fy3
ISBT #009
KIDD BLOOD GROUP SYSTEM
1951: Allen and colleagues reported finding an antibody in the serum of Mrs. Kidd, whose infant had HDFN
KIDD BLOOD GROUP SYSTEM
Antibodies have notorious reputation in blood banking (associated with Delayed HTR)
KIDD BLOOD GROUP SYSTEM
ENHANCED in enzyme treatment
KIDD BLOOD GROUP SYSTEM
Antibodies disappear rapidly both in vivo and in vitro (major reason why they cause delayed HTR)
KIDD BLOOD GROUP SYSTEM
Demonstrate dosage effect, usually warm reactive and antibodies are labile on storage
KIDD BLOOD GROUP SYSTEM
RBCs resist lysis in 2M urea
Jk(a-b-)
Rh Null antibodies =
anti-Jk-3
abundant in Polynesians; also been found in Filipinos, Indonesians, Chinese, and Japanese
Jk null
Organism with Jkb-like specificity include:
○ Enterococcus faecium
○ Micrococcus
○ Proteus mirabilis
ISBT #005
LUTHERAN BLOOD GROUP SYSTEM
Antibody was first identified in a donor’s name, Luteran
LUTHERAN BLOOD GROUP SYSTEM
Can produce a mixed field agglutination
LUTHERAN BLOOD GROUP SYSTEM
○ reacts well with saline
○ can produce mixed-field agglutination
○ thermal optimum is 12-23°C
Anti-Luª
incomplete antibody, reacts better in AHG phase
Anti-Lub
Amorphic Gene= Lu(a-b-) while Inhibitor Gene =
InLu, dominant type
Amorphic Gene= Lu(a-b-) while Inhibitor Gene =
InLu, dominant type
Antibody demonstrates a characteristic loose mixed field agglutination pattern
LUTHERAN BLOOD GROUP SYSTEM
