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DUFFY BLOOD GROUP SYSTEM (008)


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Symbol: FY Contains 5 antigens: Fya, Fyb, Fy3, Fy5, and Fy6 Fyaand Fyb are autosomal codominant antigens Fy3, Fy5, and Fy6 are high-incidence antigens present on all RBCs except the Duffy null phenotype Fy4 ?
originally described on Fy (ab) RBCs a distinct, unrelated antigen no longer included in the FY system

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DUFFY BLOOD GROUP SYSTEM


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Discovered in 1950 Named for Mr. Duffy, a multiply-transfused hemophiliac anti-Fya Anti-Fyb serum of woman who had three pregancies Null phenotype: Fy(ab)

RBCs resist infection in vitro by the monkey malaria organism, Plasmodium knowlesi RBCs also resist infection by Plasmodium vivax Also Fy: 3, 5, 6

Fy5 also not present on Rhnull RBCs regardless of the Fya or Fyb status of rbcs
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INHERITANCE: Duffy
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1q22-23, the Duffy gene (FY) Duffy gene encodes a multipass membrane glycoprotein known as Duffy glycoprotein or Duffy antigen receptor for chemokine molecule (DARC)
Expressed in other tissues, including the brain, kidney, spleen, heart, and lung Exists as a homodimer or as a hetero-oligomer with CCR5, a -chemokine receptor that plays a role in HIV internalization

Individuals who have absent or altered glycoprotein can make anti-Fy3, which will react with cells that are Fy(a+) and/or Fy(b+)
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INHERITANCE: Duffy
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Three (3) common alleles at the Fy locus: 1. Fya encode Fya antigen 2. Fyb encode Fyb antigen 3. Fy silent allele
Major allele in blacks In blacks, has been found to be an Fyb variant with a change in promoter region of the gene which disrupts the binding site for mRNA transcription in the RBC Duffy protein is expressed normally in nonerythroid cells of these persons

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INHERITANCE: Duffy
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1. 2. 3. 4.

Genetic studies have identified four Duffy alleles (Henry) FY*A Fya FY*B Fyb FY*Fy Fynull FY*X Fyx

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DUFFY BLOOD GROUP SYSTEM


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DUFFY ANTIGENS
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RBCs possess approximately 12,000 14,000 copies of DARC glycoprotein (DARC) per cell Fya is more immunogenic than Fyb

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DUFFY ANTIGENS: Fya & Fyb


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1.

2.

3.

4.

Can be identified on fetal rbcs as early as 6 weeks gestational age and are well developed at birth Expressed on endothelial cells, postcapillary venules of the kidney, spleen, heart, lung, muscle, duodenum, pancreas and placenta, and Purkinje cell neurons in the brain Fya & Fyb antigens do NOT store well in saline suspension and tend to elute from rbcs stored in a medium with low pH or low ionic strength Destroyed by common proteolytic enzymes, such as ficin, papain, bromelin, and chymotrypsin and by ZZAP
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DUFFY ANTIGENS: Fya & Fyb


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5. Not affected by AET or glycine-acid EDTA treatment 6. Neuraminidase & trypsin may reduce the MW of Fya & Fyb antigens but do not destroy antigenic activity Fy3 antigen Located on the last external loop of the Duffy glycoprotein Unlike Fya & Fyb, it is NOT destroyed by enzymes
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DUFFY ANTIGENS
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Fyx

A rare inherited form of weak Fyb Described in white populations Due to a point mutation Depressed expression of Fy3 and Fy5 antigens

Fy5 antigen
Appears to be defined by an interaction of the Duffy and Rh gene products because it is not expressed on Rhnull red cells Not destroyed by enzymes

Fy6 antigen

described only by murine monoclonal antibodies and is not present on red cells that are Fy(ab) and Fy:3,5
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DUFFY ANTIBODIES
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1. 2. 3. 4. 5.

6. 7.

8.

9.

Almost always IgG, rarely IgM React best at antiglobulin phase Some examples bind complement (IgM) A few examples are saline agglutinins Antibody activity is enhanced in a low ionic strength medium Do not react with enzyme-treated rbcs Some examples of anti-Fya and anti-Fyb show dosage Anti-Fya (common) and anti-Fyb (rare and weakly reactive) have been associated with acute and delayed HTRs Also associated with HDN (mild to severe)

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BIOLOGICAL ROLE: Duffy BGS


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1. DARC

Postulated to scavenge excess chemokines released in the circulation Chemokines chemotactic cytokines that attract white blood cells to sites of inflammation Known as a promiscuous chemokine receptor, because it binds chemokines from both the C-X-C (which includes IL-8) and C-C (which includes RANTES and monocyte chemotactic protein-1) classes May facilitate leukocyte recruitment to sites of inflammation by establishing a chemokine gradient and transporting chemokines across activated endothelium /maidafatimaestirachan'13

BIOLOGICAL ROLE: Duffy BGS


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1. DARC Can form heterodimers with the chemokine and HIV receptor CCR5, suppressing CCR5 signaling Receptor for P. vivax, which binds DARC at the Fy6 epitope 2. Fynull phenotype has been linked to lower neutrophil counts, susceptibility to infection, renal disease, and reduced graft survival following renal transplantation
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KIDD BLOOD GROUP SYSTEM


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ISBT NUMBER: 009 ISBT SYMBOL: JK Strongly associated with delayed hemolytic transfusion reactions and with intravascular hemolysis Consists primarily of two allelic antigens: Jka and Jkb
The Jka and Jkb antigens are located on the human erythroid urea transporter (UT-B), a multipass glycoprotein on chromosome 18

GENE: (JK, SLC14A1, UT-B)

More than 14,000 Kidd epitopes are present per human RBC /maidafatimaestirachan'13

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Inheritance is autosomal codominant with three predominant phenotypes A fourth phenotype, Jknull or Jk (ab), is very rare, except among Polynesians (1%) and Finns
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Null Phenotype: Jk(ab)


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Two mechanisms have been shown to produce the Jk(ab) phenotype: 1. Homozygous presence of the silent Jk allele 2. Action of a dominant inhibitor gene called In(Jk)

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KIDD BLOOD GROUP ANTIGENS


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1. 2. 3.

4.
5.

6.

Jka and Jkb are common rbc antigens Well developed on the RBCs of neonates Not very immunogenic Not denatured by papain or ficin Not affected by chloroquine diphosphate, AET, DTT or glycine-acid EDTA Not found on platelets, lymphocytes, monocytes, or granulocytes

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KIDD ANTIBODIES: Anti-Jka and Anti-Jkb


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Demonstrate dosage Often weak Anti-Jka is more frequently encountered than Anti-Jkb Usually IgG (antiglobulin reactive) Partly IgM Made in response to pregnancy or transfusion Ab reactivity can be enhanced by using LISS or PEG or by increasing the Ab/Ag ratio, or by using enzymes such as ficin or papain
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KIDD ANTIBODIES: Anti-Jka and Anti-Jkb

Many examples bind complement


Do

not store well

The titer quickly declines in vivo Difficult to detect Common cause of HTRs, especially of the delayed type Most are only rarely associated with severe cases of HDN RBCs cleared both intravascularly and extravascularly
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KIDD ANTIBODIES
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Anti-Jk3
IgG antiglobulin-reactive antibody Inseparable anti-JkaJkb Reacts with all rbcs tested except the autocontrol Reactivity is enhanced with enzyme pretreatment of the rbcs Associated with immediate and delayed HTRs and with mild HDN

Autoantibodies

Rare, but associated with AIHA Drug-related (Alpha-methyldopa, chlorpropamide) Paraben (parahydroxybenzoate)
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KIDD Blood group system


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DISEASE ASSOCIATIONS: With Jkb-like specificity:


Enterococcus

faecium

Micrococcus
Proteus

mirabilis

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Biological Significance
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1.

2.

JK/UT-B functions in the facilitated transport of urea. In kidney, transport of urea by JK/UT-B on vasa recta endothelial cells is thought to help stabilize osmotic gradients in the renal medulla during the concentration of urine.

Jknull individuals exhibit a slightly decreased capacity to concentrate urine

3.

On RBCs, JK/UT-B may help preserve the osmotic stability of RBCs as they pass through the kidney
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DIEGO BLOOD GROUP SYSTEM: 010


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ISBT Symbol: DI ISBT Number: 010 consists of 21 antigens, including four sets of allelic antigens (Wra & Wrb, Dia & Dib) DI antigens are inherited as codominant alleles on chromosome 17 Diego blood group system resides on Band 3, also known as AE1 It is estimated that nearly half of all ABO epitopes on RBCs are associated with AE1. Gene: SLC4A1
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DIEGO Antigens
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Located on the anion exchange protein, AE-1 (erythrocyte band 3) Dia antigen is rare in all populations except those of Mongolian ancestry, Asian people, and native South American Indians Expressed only on rbcs and human kidney along the collecting ducts One million copies of Diego glycoprotein (AE1) are present per RBC
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DIEGO Antigens
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The most interesting Diego antigen, however, is Wrb


The

expression of Wrb is dependent on the presence of glycophorin A RBCs lacking GYPA (En [a] phenotype) are phenotypically Wr (ab), implying that Wrb is on GYPA

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DIEGO Antigens
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DIEGO Antibodies
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Can be immune stimulated or naturally occurring Antibodies against Dia, Dib, Wrb, and ELO are usually immune stimulated IgG isotype and are detected in the AHG phase of testing Anti-Dia, anti-Dib, and anti-Wrb can be associated with decreased red cell survival, hemolytic transfusion reactions, and HDFN Anti-Wrb is also associated with autoimmune hemolytic anemia
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DIEGO Antibodies
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Antibodies against the majority of other Diego antigens are usually naturally occurring, room temperature, saline agglutinins Anti-Wra is particularly common, occurring in 1 in 100 donors. Antibodies against Wda and WARR are also fairly common, with anti-WARR reported in 13%18% of donors
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BIOLOGICAL ROLE
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Anion-exchanger 1 (AE-1)

plays an essential role in enabling the RBC to transport the waste product CO2 to the lungs, where it can be removed from the body

a chloride/bicarbonate exchanger involved in carbon dioxide transport from tissues to lungs Bind ankyrin, protein 4.2, and protein 4.1, which help to anchor and stabilize the RBC membrane to the

an integral part of the RBC membrane

underlying cytoskeleton expressed in the kidney, where it also mediates the exchange of anions

Mutations that disrupt its function can cause a renal tubular acidosis
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BIOLOGICAL ROLE
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Anion-exchanger 1 (AE-1)
may

contribute to red cell senescence Binding of hemochromes or denatured Hg to the extreme amino-terminus of AE1 is believed to play a role in Heinz body formation There is also an apparent, noncovalent association of AE1 with GYPA on RBC membranes

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CARTWRIGHT (Yt) Blood Group


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ISBT 011 Discovered in 1956 Gene: located on chromosome 7q22 consists of two autosomal codominant antigens: Yta and Ytb Yta is a high-incidence antigen expressed by 99.8% of Caucasian donors The incidence of Ytb varies by race, ranging from 0% in Japanese to 24%26% in the Mideast
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CARTWRIGHT (Yt) ANTIGENS


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located on acetylcholinesterase (AChE) Yt antigens are missing on PNH III RBCs


devoid

of all glycophosphoinositol (GPI)-linked glycoproteins

Aside from rbcs, antigens are expressed on neural synapses and neuromuscular junctions A total of 700010,000 molecules of Yt glycoprotein are present per RBC
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CARTWRIGHT ANTIBODIES
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Anti-Yta and Ytb are usually clinically benign


Shortened

red cell survival and even delayed hemolytic transfusion reactions have been reported

IgG isotype, arising from immune stimulation usually detected in the IAT Anti-Yta is more common than anti-Ytb, suggesting that Yta is the more immunogenic antigen Neither antibody is associated with HDFN
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Biological Role: CARTWRIGHT


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Acetylcholinesterase (AChE) is a critical enzyme required for the rapid degradation of acetylcholine on postsynaptic membranes of nerves and muscles Role of AChE in RBCs is unknown

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XG BLOOD GROUP SYTEM:012


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Contains a single antigen, Xga Only two phenotypes: Xga-positive and Xganegative Antigen is encoded by a gene on the X chromosome Among Caucasians, approximately 89% of women and 66% of men are Xga-positive Approximately 9000 molecules of Xga are present per RBC
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XG BLOOD GROUP Antibodies


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Anti-Xga is not associated with hemolytic transfusion reactions or HDFN may be immune stimulated or naturally occurring Most examples are of IgG isotype, including some capable of activating complement

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SCIANNA BLOOD GROUP SYSTEM : 013


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Contains seven antigens: SC1 SC7 Sc2 and Sc4 are low incidence Specific for RBCs and erythropoietic tissues Antigens reside on ERMAP
A

member of Ig superfamily (like Lutheran, Ok, and LW proteins type 1 single-pass transmembrane protein ERMAP gene resides on chromosome 1p34

The antigens are relatively resistant to enzymes but can be weakened with DTT and AET
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SCIANNA BLOOD GROUP SYSTEM: ANTIBODIES


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Rare and generally benign Usually of IgG isotype with some examples binding complement Most examples are immune stimulated

naturally occurring anti-Sc2 antibodies are known

Not a cause of transfusion reactions Anti-Sc4 and anti-Sc2 have been associated with HDFN Autoantibodies against Sc1 and Sc3 antigens have been associated with warm autoimmune hemolytic anemia Antibodies can be neutralized with soluble recombinant ERMAP protein
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Biological Role: SCIANNA


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The biological role of ERMAP is unknown, although its structure suggests that it may play a role in RBC adhesion and signaling It is speculated that ERMAP could be involved in immune recognition and autoimmune anemia

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DOMBROCK BLOOD GROUP SYSTEM: 014


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contains seven antigens Doa (DO1) and Dob (DO2) are autosomal codominant antigens
expressed

by 67% and 82% of white donors, respectively

Gene for Dombrock (ART4) is located on chromosome 12p13.2-12.1 Gya, Hy, Joa, DOYA, and DOMR are highincidence antigens found on virtually all donors
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DOMBROCK : Null Phenotype


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The Donull or Gy(a) phenotype is a rare, autosomal recessive phenotype Acquired Donull phenotype can be observed in paroxysmal nocturnal hemoglobinuria type III (PNH-III)
characterized

by chronic hemolysis due to an absence of all GPI-linked glycoproteins, including Cromer, Dombrock and Cartwright antigens

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DOMBROCK ANTIGENS
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Dombrock antigens reside on an adenosine diphosphate (ADP)-ribosyltransferase (CD297)


catalyzes

the transfer of ADP-ribose from nicotinamide adenine dinucleotide (NAD) to a protein acceptor

Dombrock can be destroyed by:


disulfide reducing agents phosphatidylinositol phospholipase C

cleaves

GPI-linked proteins
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DOMBROCK ANTIBODIES
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Can be clinically significant, although many examples are benign usually of IgG isotype arising from immune stimulation by transfusion or pregnancy Antibody reactivity can be enhanced by the use of papain- or ficin-treated RBC Antibody reactivity is reduced or abolished by the treatment of red cells with sulfhydryl-reducing agents (DTT, AET), trypsin, chymotrypsin, and pronase
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DOMBROCK ANTIBODIES
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can deteriorate with in vitro storage, complicating pretransfusion testing titers may decrease over time in vivo, falling below the level of detection Commonly found in mixtures of alloantibodies and can be difficult to identify capable of causing shortened RBC survival and acute and delayed hemolytic transfusion reactions Not associated with HDFN
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COLTON BLOOD GROUP SYSTEM: 015


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Initially identified in 1967 Consists of two autosomal codominant antigens, Coa and Cob, and a third high-incidence antigen (TOR) Coa is a high-incidence antigen present on 99.7% of donors Cob is expressed by less than 11% of donors, with only 0.3% being Co (ab+) antigens are expressed on RBCs, renal proximal tubules, thin descending limb of Henle, renal vasa recta endothelium, choroid plexus, ciliary body, microvessels, gallbladder, placenta, and some epithelial cells More than 120,000160,000 molecules of Colton glycoprotein are present per RBC
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COLTON BLOOD GROUP SYSTEM: 015


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antigens reside on aquaporin 1 (AQP-1) or channel-forming integral protein multipass integral membrane protein containing six transmembrane domains

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COLTON ANTIGENS
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reside on aquaporin 1 (AQP-1) or channelforming integral protein (CHIP 28)


Functions

as the red cell water transporter

antigens are products of a gene on chromosome 7

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COLTON ANTIBODIES
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can be clinically significant


can

be associated with shortened RBC survival, hemolytic transfusion reactions, and HDFN

usually of the IgG isotype resulting from immune stimulation by transfusion or pregnancy Some examples of anti-Coa and anti-Cob are reported to bind complement detectable in the AHG phase of testing enhanced with protease-treated RBCs
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COLTON ANTIBODIES
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Rare Conull and TOR-negative individuals can make an anti-Co3 (anti-Coa+b)


alloantibody

that reacts with both Co (a+b) and Co (ab+) RBCs

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COLTON ANTIBODIES
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Rare Conull and TOR-negative individuals can make an anti-Co3 (anti-Coa+b)


alloantibody

that reacts with both Co (a+b) and Co (ab+) RBCs

BIOLOGICAL ROLE: 1. AQP-1 is a major molecular water channel on RBCs that facilitates the concentration of urine in kidney 2. Conull red cells also have decreased CO2 permeability
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LW BLOOD GROUP SYSTEM: 016


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Landsteiner-Wiener blood group system most important for its role in the history of the Rh blood group system originally developed antibodies against the LW antigens by immunizing rabbits with rhesus monkey red cells resulting anti-Rh antibodies were initially believed to recognize the RhD antigen the antibodies developed by Landsteiner and Wiener recognized a non-Rh (LW) antigen
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LW BLOOD GROUP SYSTEM: 016


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Consists of two allelic antigens: LWa and LWb LWa is a high-frequency antigen (99% of white donors) Expression of LWa antigen is dependent on RhD protein expression
Highest

expression observed on RhD-positive red cells and weaker expression on RhD-negative cells

LW antigens are absent from Rhnull erythrocytes LW antigen is expressed on RBCs and placenta Approximately 36005000 molecules of LW glycoprotein are present per RBC

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LW BLOOD GROUP SYSTEM: 016


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Antigens are destroyed by sulfhydryl reagents and pronase


unaffected

by papain or ficin

LW antigens reside on intracellular adhesion molecule type 4 (ICAM4, CD242)


member

of the Ig superfamily

ICAM4 gene resides on chromosome 19p13

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LW ANTIBODIES
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Clinically benign Rarely a cause of hemolytic transfusion reactions or HDFN usually are of IgG isotype detected in the IAT Antibody activity can be reduced by:
ethylenediaminetetraacetic acid (EDTA) pretreatment of RBCs with sulfhydryl-reducing agents (DTT, AET)

LWnull individuals can make an anti-LWab, which reacts with both LW (a+b) and LW (ab+) erythrocytes
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LW BLOOD GROUP SYSTEM: BIOLOGICAL ROLE


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1.

LW glycoprotein is a

potential counterreceptor for the a2-integrin protein Mac1 (CD11b/CD18), LFA-1 (CD11a/CD18), and platelet GPIIb/IIIa participate in adhesive interactions during early erythroid development may also be involved in red cell senescence by binding to CD11/CD18 integrin on splenic macrophages

2.

LW expression is elevated in sickle cell patients and may be involved in microvascular occlusion
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CHIDO/RODGERS BGS: 017


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contains 10 antigens Most Ch/Rg antigens are high-incidence antigens (>90%) Gene located on chromosome 6p21.3

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CHIDO/RODGERS ANTIGENS
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Ch/Rg antigens are antigenic determinants on the C4d fragment of the C4 complement molecule

Chido antigens are on C4B and Rodgers antigens are on C4A

Ch/Rg antigens are of plasma origin and are passively adsorbed onto RBC membranes Ch/Rg antigens are weakly expressed on cord RBCs and some GYPA-deficient RBCs Destroyed by papain/ficin treatment but unaffected by DTT/AET treatment

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CHIDO/RODGERS ANTIGENS
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Chido/Rodgers Antibodies
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Historically, were grouped as high-titer, low avidity (HTLA) Do not cause hemolytic transfusion IgG isotype (IgG2 & IgG4) and are usually detected with AHG Do not cause hemolytic transfusion reactions or HDFN Antibody reactivity can be enhanced by incubating RBCs in a lowionic sucrose solution Activity can be inhibited by pooled plasma from antigen-positive individuals or by treatment of RBCs with proteases
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Chido/Rodgers: Biological Significance


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1.

2.

C4 deficiency is associated with autoimmune disorders and susceptibility to bacterial meningitis Specific C4 allotypes have been linked to several autoimmune disorders, including rheumatoid arthritis and Graves disease

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GERBICH BLOOD GROUP SYSTEM:020


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Ge has 7 antigens; 3 high-frequency (Ge2, Ge3, Ge4); 4 low-frequency (Wb (Webb)/Ge5, Lsa, Ana/Ge7, and Dha/Ge8 Found on fetal and adult rbcs, platelets, kidney, and fetal liver Encoded by chromosome #2 (GYPC gene) Expressed on 2 glycoproteins, Glycophorin C and Glycophorin D GPC & GPD interacts with spectrin, band 4.1 and p55

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Null Phenotypes in Gerbich


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1. 2.

3.

Three autosomal recessive phenotypes: Yus (Ge 2,3,4) Gerbich (Ge 2,3,4) Leach (Ge 2,3,4) two types: PL (deletion of exons 3 &4) and LN (deletion of nucleotide 134)

Elliptocytosis

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Gerbich Antigens
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Ge2, Ge3 and Ge4 antigens resistant to standard reducing agents Ge3 resistant to ficin and papain but sensitive to trypsin Gerbich antigens decreased in patients with hereditary elliptocytosis due to protein 4.1 deficiency (integral for maintaining normal erythrocyte skeleton and shape)

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Gerbich Antibodies
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Predominantly IgG RBC-stimulated Variably binding complement Can be detected at room temperature Reacting in the indirect antiglobulin phase of testing (IAT) Anti-Ge2 and anti-Ge3 also non-rbc stimulated IgM immunoglobulins and as autoantibodies (associated with severe AIHA) Causes acute to delayed HTR but not HDN
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Gerbich Antibodies
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Antibodies to the low-incidence antigens: anti-Wb, anti-Lsa, anti-Ana, and anti-Dha


Predominantly

IgG with an IgM component Not binding complement

Anti-Wb and anti-Lsa generally non-rbc stimulated

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BIOLOGICAL ROLE
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GPC/GPD help anchor the membrane to the underlying skeleton (like Diego/Band3)
Can

bind influenze virus (rich in sialic acid) May bind P. falciparum

In patients with hereditary elliptocytosis and protein 4.1 deficiency, GPC/GPD are decreased (75% of normal) Leach phenotype associated with marked elliptocytosis (due to reduced membrane stability and deformability)
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CROMER Blood Group System (ISBT No. 021)


Cr/CROM High incidence: Cra, Tca, Dra, Esa, IFC, UMC, WESb and GUT1 Low incidence: Tcb, Tcc, WESa Present on Decay accelerating Factor (DAF or CD55) Locus for CROM antigens: Chromosome #1 DAF widely expressed on tissues and secretions
Identified

on all hematopoietic cells, vascular endothelium, gastrointestinal and genitourinary epithelium), brain and body fluids
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Cromer Antigens
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Sensitive to chymotrypsin and pronase treatment Resistant to all other enzymes Weakened, but not destroyed by AET & DTT All are carried by DAF DAF involved in the regulation of complement activation by accelerating the decay of C3 and C5 convertases
Serves

as an integral intrinsin membrane glycoprotein that is anchored by GPI


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Null Phenotype (CROMER)


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Inab or Cromer null phenotype lacks all CROM antigens as well as DAF
Rare

autosomal recessive phenotype Normal expression of CD59 and other glycosyl phosphoinositol (GPI)-linked glycoproteins Linked with chronic intestinal conditions (DAF is attachment site for E. coli on epithelial cells)
Chronic

protein-losing gastroenteropathy

Dr(a ) phenotype weak Cromer expresssion (40% normal)


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CROMER Antibodies
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Predominantly IgG1 RBC-stimulated Reactive in IAT testing (Weak, variable HTLA) Neutralization can be accomplished with concentrated serum, plasma, platelet concentrates or urine Anti-Cra associated with mild transfusion reactions Maternal antibodies (placenta carries high levels of DAF) to Cromer antigens absorbed onto the tissue thereby limiting occurrence of HDN
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CROMER Antibodies
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Antibody reactivity is highly sensitive to pretreatment with chymotrypsin and pronase but not to other proteases BIOLOGICAL ROLE:
CD55/DAF
Receptor

protects cells from complement

for uropathogenic and intestinal E. coli strains bearing Afa/Dr and X adhesins, echovirus and Coksackie B virus

CD55/CROMER

missing on PNH III rbcs

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KNOPS Blood Group System (ISBT No. 022)

Contains 8 antigens (Kna (Knops), Knb, McCa (McCoy), Sl1 (Swain-Langley), Yka (York), McCb, Sl2 (Vil) and Sl3 Knops antigens are present on adult and cord rbcs, neutrophils, B lymphocytes and dendritic cells Knops antigens reside on Complement receptor type 1 (CR1 or CD35) CR1 gene resides on chromosome 1
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Knops Antigens
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Resistant to ficin/papain treatment but destroyed of weakened by trypsin, achymotrypsin, and reducing agents such as DTT Expressed poorly on cord rbcs Depressed in patients presenting with autoimmune disease and the Lu(ab) phenotype due to the influence of the In(Lu) gene
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KN Antibodies
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Formerly described as having the serologic properties of HTLA IgG RBC- stimulated Weak and variable reaction in IAT phase of testing Little clinical significance ( None have been attributed to causing clinical HDN or HTR) Reactivity could mask the presence of an underlying antibody of clinical significance

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Biological Role
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CR1 can bind C3b/C4b immune complexes, promoting their degradation by factor 1
Enhances

phagocytosis of C3b/C4b coated-

paricles Could play a role in Leishmania, Mycobacteria and Legionella infections Also binds P. falciparum with rosette formation (a clinical finding with severe malaria)

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Biological Role
81

Certain autoimmune diseases such as SLE and Chronic cold agglutinin disease depresses the expression of KN antigens due to loss of erythrocyte CR1

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INDIAN Blood Group System ISBT No. 023)


Antigens are inherited as codominant alleles on chromosome 11 IN Ina (low incidence) higher in Iranians and Arabs, much lower in whites, blacks, Asians Inb (high-incidence) 96% of whites and 96% of Indians AnWj another high incidence antigen believed to belong to the Indian BGS

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Indian Antigens
83

Reside on CD44 glycoprotein CD44 widely expressed on all hematopoietic cells, epithelial cells and neural tissue
Major

component of the rbc membrane Involved in B- and T-cell activation, WBC adhesion activities and other immune-mediated interactions

Antigens denatured by most enzymes and reducing agents


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Indian Antigens
84

Effective immunogens Poorly expressed on cord rbc and probably depressed in pregnancy Inb expression is depressed in individuals with Lu(ab) phenotype owing to the In(Lu) gene

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Indian Antibodies
85

IgG RBC-stimulated Reactive in IAT testing Anti-Inb causing HTR Neither antibodies causes HDN

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Biological Role
86

CD44 a major adhesion molecule on leukocytes binds a spectrum of extracellular matrix proteins, including collagen, fibronectin, laminin and hyaluron In bone marrow, may participate in the adhesion of erythroid progenitors to stromal fibroblasts In leukocytes, may facilitate WBCendothelial adhesion, helping to localize WBC to sites of inflammation has been implicated in tumor metastasis, wound remodeling, and embryonic differentiation AnWj/CD44 Receptor for Haemophilus influenzae
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87

OK Blood Group System (ISBT No. 024)


Single high freqency antigen:Oka Oka glycoprotein is present on RBCs, WBCs and hematopoietic progenitors Resides on CD147 Gene found on chromosome 19 CD147 member of the Ig superfamily a leukocyte-activation-associated protein and may participate in cell adhesion, tumorigenesis and wound healing via stimulation of enzymes required for remodeling of the extracellular matrix

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Antigen and Antibody


88

Oka antigen is resistant to enzymes, sialidases and sulfhydryl-reducing agents Anti-Oka rare and described only in Japan
IgG

isotype arising from immune stimulation associated with shortened RBC survival following transfusion of Oka-incompatible RBCs

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89

RAPH Blood Group System (ISBT No. 025)


Single antigen RAPH or MER2 RAPH is expressed by 92% donors and can vary in strength Present on CD34+ cells, fibroblasts and RBCs There is a progressive decrease in RAPH/MER2 expression with increasing erythroid maturation expressed on MER2 encoded by chromosome # 11
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90

JMH Blood Group System (ISBT No. 026)

John Milton Hagen (JMH) BGS contains a single, high-incidence antigen, JMH Found on lymphocytes, activated macrophages, thymus, brain, respiratory epithelium, placenta, testes and spleen JMH is carried on CD108 (SEMA-L), a semaphorin family glycoprotein The molecule is anchored into the cell membrane by a glycophosphoinositol tail (GPIlinked) and is absent on PNH III RBCs Chromosome # 15
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JMH Antigens & Antibodies


91

JMH antigen is sensitive to proteases and DTT Antibodies:


do

not cause hemolytic transfusion reactions or HDN although shortened RBC survival has been documented IgG isotype and can be naturally occurring

BIOLOGICAL ROLE: Semaphorin proteins are implicated in cell signaling


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I Blood Group System (ISBT No. 027)

contains two biosynthetically related antigens: I and i I & i are on the same carbohydrate chains that carry RBC ABO antigens Both I and i antigens are ubiquitously expressed on glycolipids and glycoproteins on red cells and other tissues HISTOBLOOD GROUP ANTIGENS The I antigen is derived from i antigen
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I Blood Group System: 027


93

i antigen
found predominantly on fetal and infant RBCs a linear oligosaccharide containing at least two successive lactosamine epitopes

I antigen
derived from i antigen by the action of a 16 Nacetylglucosaminyltransferase the product of the GCNT2 or IGnT gene on chromosome 6p24

***Both i and I can be further modified by other glycosyltransferases to yield ABH, LeX, and related antigens
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Elevated i
94

Seen in HEMPAS (hereditary erythroblastic multinuclearity with positive acidified-serum test


congenital

dyserythropoietic anemia associated with chronic hemolysis, binucleated erythroblasts, and altered red cell glycosylation

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ANTIBODIES
95

IgM isotype, reactive at room temperature Autoantibodies to I are relatively common and are usually low-titered cold agglutinins Some anti-I can have IH specificity, reacting stronger with group O and A2 RBC

Anti-i
has

uncommon

been reported in:

CAIHA Infectious mononucleosis Choriocarcinomatosis Alcoholic cirrhosis


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ANTIBODIES
96

Autoanti-i
May

be seen as a relatively weak cold autoagglutinin reacting preferentially at 4 C Reacts strongest with cord and i adult red cells, and weakest with I adult red cells Patients with infectious mononucleosis often have transient but potent anti-i.

Alloanti-I
Exists

as IgM or IgG relatively rare and is found as a naturally occurring antibody in iadult individuals
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ANTIBODIES
97

Anti-I
Incubating

tests in the cold enhances reactivity and helps to confirm its identity Albumin and testing enzyme-treated red cells also enhance reactivity

Autoanti-I
pathologic

significance in cold agglutinin syndrome (CAS) behaves as a complement-binding antibody with a high titer and high thermal amplitude often made by patients with pneumonia due to Mycoplasma pneumoniae
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BIOLOGICAL ROLE: I
98

Despite the common occurrence of major maternal-fetal ABO incompatibility, severe HDFN due to ABO incompatibility is rare (0.04%) Developmental delay in I antigen synthesis may play a protective role against HDFNABO

by minimizing the number of ABH antigens expressed on fetal red cells

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99

GIL Blood Group System (ISBT No. 029)


Contains one high-incidence antigen: GIL GIL protein is highly expressed on RBCs, kidney, small intestine, stomach, colon, spleen, eye and respiratory tract
carried

by aquaglyceroporin (AQP3)
of the MIP family of water channels

member

AQP3 gene chromosome no. 9

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GIL antigen and antibody


100

The antigen is resistant to proteases, sialidases and DTT Antibody Anti-GIL is associated with hemolytic transfusion reactions no reports of clinical HDN due to anti-GIL despite a positive direct antiglobulin test (DAT) IgG isotype, reactive at 37C and enhanced with AHG BIOLOGICAL ROLE: a membrane water channel capable of transporting urea and glycerol

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101

The Miscellaneous WBC antigens: Bg


Bg: Bennet-Goodspeed Antibodies directed towards HLA Bga corresponds to HLA-B7 Bgb corresponds to HLA-B17 Bgc corresponds to HLA-A28 These antigens are expressed variably on RBC s

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BLOOD GROUP COLLECTIONS

102
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High Incidence Antigens (901 Series)

103
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Low-Incidence Antigens (700 Series)

104
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UPDATES
105

P1Pk System (formerly P System) Chromosome 22 2 Antigens!


P1

and Pk

Globoside System: P is the only antigen Globoside Collection: PX2 and LKE antigens More changes to come based on molecular technology!
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UPDATES
106

Lewis System Chromosome 19 6 Antigens


Lea, Leb Leab, LebH, ALeb, BLeb

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UPDATES
107

6th Dombrock Antigen: DOYA


Study

published in Transfusion, Volume 50, Issue 6 (June 2010) by Mayer, et al. A patients DO genes have a single nucleotide change. DOYA (possible high incidence antigen) not present. Causes no expression of Doa and weakened expression of Hy, Joa, and Gya antigens

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UPDATES: Criteria for the inclusion of a new specificity in an established system


108

1. 2.

3.

4.

An antithetical relationship between a new antigen and one already assigned to the system. Demonstration that expression of the antigen is associated with a variation in the nucleotide sequence of the gene controlling the system. Evidence, from a linkage analysis of family data, that the controlling allele is probably a newly recognised form of the pertinent gene, and supporting serological or biochemical information. Demonstration that an antigen is located on a protein or glycoprotein that carries other antigens belonging to the system.

could result from post-translational modification of a gene product, such as glycosylation, which would not support inclusion within the system.
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References
109

Brecher, Mark E. Technical Manual. 15th ed. Bethesda, MD: AABB, 2005. Daniels G. Human Blood Groups. 2nd ed. Cambridge, MA: Blackwell Science, 2002. Harmening DM. Modern Blood Banking and Transfusion Practices. 5th ed. Philadelphia, PA: F. A. Davis Co., 2005. Hillyer, Christopher D, Shaz, Beth H, et al. Transfusion Medicine and Hemostasis. New York, NY: Elsevier Inc. 2009 McPherson, Richard A., Pincus, Matthew R. Henrys Clinical Diagnosis and Management by Laboratory Methods . 22 nd ed. Philadelphia, PA: Elsevier Saunders, 2011 Storry JR, Castilho L, et al. International Society of Blood Transfusion Working Party on red cell immunogenetics and blood group terminology: Berlin Report. Vox Sang 2011. http://ibgrl.blood.co.uk/isbt%20pages/ISBT%20Terminology%2 0Pages/Terminology%20Home%20Page.htm
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