W10TL4 - Other Blood Groups Flashcards
Lewis Blood Group Antigens
Two major ag’s - Lea and Leb
CHO in nature
Ag’s are secreted from tissues then adsorbed → RBC
A single L-fucose moiety differentiates the two ag’s
- added by α-1,4-L fucosyltransferase
- encoded by FUT3 (Le) gene
- inheritance is dominant, so only 1 Le allele (Lele) needs to be present for expression
- acts on Type 1 precursor substance only
- added to GlcNAc residue of Type 1 precursor substance
Antigen expressed depends on inheritance of FUT3 and FUT2
Lewis Blood Group Antibodies
Naturally occurring, IgM
Anti-Lea is only produced by Le(a-b-) individuals
Anti-Leb is rarely seen
Occur more frequently during pregnancy
Are rarely clinically significant
- Lewis Ag are poorly developed at birth, and IgM antibodies can’t cross the placenta
- neutralised by Lewis Ag’s in plasma
- Lewis Ag dissociate from transfused RBC membrane
Can cause HTR if they react at 37°C or IAT
I System
I is the only antigen in the I blood group
A second related antigen, i, is found in the Ii blood collection
Both are produced by glycosyltransferases
- each enzyme is encoded by a different gene
An alloantibody to the i antigen has not been identified
I System Antigens
Two major antigens - i and I CHO in nature - i is linear; I is branched - IGnT encodes the glycosyltransferase responsible for branching High incidence Ag that vary with age - 0-18 months = i is expressed on RBCs - 18+ months = I is expressed on RBCs - some adults don’t convert from i → I = adult i phenotype Precursors to the Lewis and ABO antigens
I System Autoanti-I
IgM
Found in virtually all sera but is usually benign
Reacts optimally at 4°C
Strongly agglutinates adult RBCs, weakly agglutinates cord RBCs
Can cause problems during pre-transfusion testing if it reacts @ RT
Pathogenic autoanti-I reacts at 32°C and seen in cold agglutination syndrome
Compound Anti-I Antibodies
I is found on the same structure as the ABO and Le ag’s
Therefore aby’s against complex ag’s are produced
- require presence of both ag’s for reactivity
Anti-HI is an example
- reacts most strongly with cells expressing both H and I ag’s i.e. O and A2 cells
- reacts weakly with cells expressing low levels of H or I ag
P Blood Group Antigens
CHO in nature Produced by the addition of CHO residues to a precursor substance by glycosyltransferases Three major antigens: - P (028), P1 and Pk (003) Five (5) RBC Phenotypes - P1 (P1, P ag's on surface) - P2 (P ag on surface) - p (no ag on surface) - P1k (P1, Pk ag's on surface) - P2k (P, Pk ag's on surface) P1 antigen deteriorates during storage → false neg’s
P Blood Group Antibodies
Anti-P1
- naturally occurring IgM antibody in P1 neg individuals
- cold reacting, only clinically significant if it reacts @ 37°C
- can cause issues during pre-transfusion testing
Anti-PP1Pk
- naturally occurring IgM and IgG found in p individuals
- mixture of anti-P, anti-P1, and anti-Pk antibodies
- react over wide thermal range, can bind complement
- cause HTR and HDNB, assoc. w/ spontaneous abortion
Anti-P
- naturally occurring in p and Pk individuals
- wide thermal range, can cause HTR and HDNB
- autoantibody is assoc. w/ paroxysmal nocturnal haemoglobinuria
Rh Blood Group
C, c, D, E, e
Non-glycosylated proteins
D antigen is highly immunogenic
Enhanced by enzyme treatment
C and c, and E and e, are antithetical (also demonstrate dosage)
Two closely linked loci, RHD and RHCE encode antigens
- RHD encodes D antigen
- RHCE encodes C/c and E/e antigens
Presence of RHD on one or both alleles = D antigen expressed (Rh(D) pos)
Rh(D) neg individuals result from multiple genetic mutations
Causes of Rh(D) Negative Individuals
- Absence of RHD on both alleles
- Presence of the RHD pseudogene (RHDψ)
- most common cause of Rh(D) neg in Africans (67% of all Rh(D) neg)
- 37bp duplication of the intron 3-exon 4 boundary introduces a stop codon in exon 6
- mRNA is not produced from the gene, therefore there is no D protein - Presence of a RHD-CE-D hybrid gene
- accounts for 15% of Rh(D) neg in Africans
- the region of the RHCE gene encoding part of exon 3 through to exon 8 is present in the RHD locus
Wiener and Fisher Race Nomenclature
R = D r = d (absence of D, no d antigen) C + e = R1 or r' c + E = R2 or r" c + e = R0 or r C + E + d = ry C + E + D = Rz
Weak D
Expression of the entire/complete antigen is decreased resulting from mutations in RHD
Express complete D antigen so therefore are Rh(D) pos
Multiple mechanisms result in a weak D phenotype:
1. C in trans to D
- also known as the Ceppelini effect
- when C is on the opposite haplotype to D, D antigen expression is decreased
- i.e. Dce/dCe individual express less D antigen on their RBCs than a DCe/dce individual
2. Del
- extremely low expression of D antigen
- reported only in Asian populations
- type Rh(D) neg
- D ag expression identified using adsorption/elution techniques
Partial D
Regions of RHD are replaced by regions of RHCE
Protein product is missing part of the D antigen
Partial D individuals are considered either Rh(D) negative OR Rh(D) positive, depending on the whether they are a recipient or donor
Recipient
- partial D individuals express only part of the D antigen
- can produce an anti-D antibody if exposed to the complete D antigen
- partial D recipients should be typed as Rh(D) neg
Donor
- partial D antigen is immunogenic
- it can stimulate the production of anti-D, and can cause HTRs
- partial D donors should be typed as Rh(D) pos
DVI- and DVI+ on Agglutination Cards
In Australia, the most common type of anti-D antibodies used is DVI
DVI-
- anti-D won’t agglutinate DVI RBCs
- DVI individuals will be typed as Rh(D) neg
DVI+
- anti-D will agglutinate RBCs
- DVI individuals will be typed as Rh(D) pos
Kell Blood Group
K and k
Antithetical, expressed in a co-dominant fashion
Well developed at birth
K is relatively highly immunogenic
Not destroyed by enzymes, but are by reducing agents such as DTT or AET
Kell Blood Group Antibodies
Anti-K - IgG - best detected by IAT at 37°C - causes HTR and HDNB Anti-k - very rare - IgG, detected by IAT at 37°C - can be difficult to find compatible units for individuals who produce it
Other Kell Blood Group Antigens
Kpa and Kpb, Jsa and Jsb
Either high incidence (Kpb, Jsb) or low incidence (Kpa, Jsa)
Therefore antibodies are rarely encountered
- most people express Kpb and Jsb, so aby’s aren’t produced
- most people never encounter Kpa or Jsa, so aby’s aren’t common
Aby’s are similar to anti-K in characteristic and clinical significance
McLeod Phenotype
XK is required for optimal Kell Ag expression
- XK is NOT a Kell Ag itself, but within its own blood group
Individuals lacking XK have McLeod Phenotype
- v. rare, X-linked disease (1:100k)
- v. weak Kell ag expression - acantho, aniso, ↑ retic’s, ↑ osmotic fragility, ↓ haptoglobin
- cardiomyopathy
- neurologic defects
- individuals with chronic granulomatous disease (CGD) can have a similar phenotype
Kell Null Phenotype
Ko allele = silent
Inheritance of KoKo => RBCs lacking ALL Kell Ag’s
- i.e. K null
- rare (1:25k)
- express XK at ↑ amounts
K null individuals can produce a “universal Kell” aby
- named anti-Ku
- recognises a Kell structure present on all but Ko RBCs
- causes HTR and HDNB
Kidd Blood Group
Two major antigens: Jka and Jkb Jk3 is an ag common to all Jk pos cells Antithetical, expressed in a co-dominant fashion Well developed at birth Poor immunogens Reactivity is enhanced by enzymes
Kidd Blood Group Antibodies
Anti-Jka and anti-Jkb - usually IgG - difficult to work with - demonstrate dosage - weak - found in combination with other aby’s - titre quickly declines in vivo - not stable on storage - common cause of delayed HTR, rarely cause HDNB Anti-Jk3 - reacts to all Jk pos cells - causes HTR and mild HDNB
MNS Blood Group
Consists of 5 major antigens
- M and N
- expressed on glycophorin A (GPA; encoded by GPA)
- destroyed after enzyme treatment of RBCs - S and s
- expressed on glycophorin B (GPB; encoded by GPB)
- destroyed after enzyme treatment (except by trypsin) - U
- universal antigen
- expressed on GPB
- not destroyed by enzymes
MNS Antibodies
Anti-M and anti-N - usually naturally occurring aby’s that react below 37°C - IgM or IgG - don’t react with enzyme treated cells - demonstrate dosage - clinically significant when reactive in IAT @ 37°C Anti-S and anti-s - IgG, react @ 37°C, detected by IAT - demonstrate dosage - can cause HTR and HDNB - can be difficult to find compatible units for individual w/ anti-s Anti-U - produced in S- s- U- individuals - immune - will react to all panel cells, and enzyme treated cells - can cause HTR and HDNB
Duffy Blood Group
Consists of five antigens
- Fya and Fyb (most common)
- antithetical, expressed in a co-dominant fashion
- well developed at birth
- destroyed after enzyme treatment of RBC
- Fy3, Fy5 and Fy6
Duffy Blood Group Antibodies
IgG, detected best by IAT Anti-Fya more common than anti-Fyb Demonstrate dosage Don’t react with enzyme treated cells Cause acute and delayed HTR and mild to severe HDN
Duffy Blood Group Fyx
FYX allele
Results in weak expression of Fyb [written Fy(b+w)]
RBCs type Fy(b-) with most antibodies
- Fyb expression is identified via adsorption/elution
Importantly, these individuals cannot produce anti-Fyb aby’s
- therefore can receive Fy(b+) RBCs
Lutheran Blood Group
Two major antigens: Lua and Lub Antithetical, expressed in a co-dominant fashion Poorly developed at birth Weakly immunogenic Lu(a-b+) has highest frequency
Lutheran Antibodies
Rarely encountered in the laboratory
Anti-Lua
- naturally occurring, IgM, react best at RT (some will react @ 37°C by IAT)
- mixed field reactivity by tube method
Anti-Lub
- immune, IgG, react best @ 37°C by IAT
- reacts with all panel cells except auto
Colton Blood Group
Two major antigens: Coa and Cob Found on aquaporin-1 - water transporter Antithetical, expressed in a co-dominant fashion Cob is a poor immunogen Co(a+b+) has highest frequency
Colton Group Antibodies
IgG, detected using the IAT Detection is enhanced by using enzyme treated cells Anti-Coa - rarely encountered in the laboratory - can cause HTR and HDNB - difficult to find compatible cells Anti-Cob - can cause HTR and mild HDNB
