Blood Group Systems

2/3/2013
DUFFY BLOOD GROUP SYSTEM (008)

2
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
/maidafatimaestirachan'13
2/3/2013
DUFFY BLOOD GROUP SYSTEM

3
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
4
2/3/2013
INHERITANCE: Duffy
5
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+)
6
2/3/2013
INHERITANCE: Duffy
7
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
INHERITANCE: Duffy
8
1. 2. 3. 4.
Genetic studies have identified four Duffy alleles (Henry) FY*A Fya FY*B Fyb FY*Fy Fynull FY*X Fyx
2/3/2013
DUFFY BLOOD GROUP SYSTEM

9
DUFFY ANTIGENS
10
RBCs possess approximately 12,000 14,000 copies of DARC glycoprotein (DARC) per cell Fya is more immunogenic than Fyb
2/3/2013
DUFFY ANTIGENS: Fya & Fyb

11
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
DUFFY ANTIGENS: Fya & Fyb

12
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
2/3/2013
DUFFY ANTIGENS
13
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
DUFFY ANTIBODIES
14
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)
2/3/2013
BIOLOGICAL ROLE: Duffy BGS

15
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

16
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
2/3/2013
KIDD BLOOD GROUP SYSTEM

18
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
2/3/2013
19
Inheritance is autosomal codominant with three predominant phenotypes A fourth phenotype, Jknull or Jk (ab), is very rare, except among Polynesians (1%) and Finns
Null Phenotype: Jk(ab)

20
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)
10
2/3/2013
KIDD BLOOD GROUP ANTIGENS

21
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
KIDD ANTIBODIES: Anti-Jka and Anti-Jkb

22
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
11
2/3/2013
23
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
KIDD ANTIBODIES
24
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)
12
2/3/2013
KIDD Blood group system

25
DISEASE ASSOCIATIONS: With Jkb-like specificity:

Enterococcus
faecium
Micrococcus
Proteus
mirabilis
Biological Significance
26
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
13
2/3/2013
DIEGO BLOOD GROUP SYSTEM: 010

27
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
DIEGO Antigens
28
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
14
2/3/2013
DIEGO Antigens
29
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
DIEGO Antigens
30
15
2/3/2013
DIEGO Antibodies
31
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
DIEGO Antibodies
32
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
16
2/3/2013
BIOLOGICAL ROLE
33
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
BIOLOGICAL ROLE
34
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
17
2/3/2013
CARTWRIGHT (Yt) Blood Group

36
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
18
2/3/2013
CARTWRIGHT (Yt) ANTIGENS

37
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
CARTWRIGHT ANTIBODIES
38
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
19
2/3/2013
Biological Role: CARTWRIGHT

39
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
XG BLOOD GROUP SYTEM:012

40
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
20
2/3/2013
XG BLOOD GROUP Antibodies

41
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
SCIANNA BLOOD GROUP SYSTEM : 013

42
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
21
2/3/2013
SCIANNA BLOOD GROUP SYSTEM: ANTIBODIES

43
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
Biological Role: SCIANNA

44
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
22
2/3/2013
DOMBROCK BLOOD GROUP SYSTEM: 014

45
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
DOMBROCK : Null Phenotype

46
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
23
2/3/2013
DOMBROCK ANTIGENS
47
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
DOMBROCK ANTIBODIES
48
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
24
2/3/2013
DOMBROCK ANTIBODIES
49
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
COLTON BLOOD GROUP SYSTEM: 015

50
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
25
2/3/2013
COLTON BLOOD GROUP SYSTEM: 015

51
antigens reside on aquaporin 1 (AQP-1) or channel-forming integral protein multipass integral membrane protein containing six transmembrane domains
COLTON ANTIGENS
52
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
26
2/3/2013
COLTON ANTIBODIES
53
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
COLTON ANTIBODIES
54
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
27
2/3/2013
COLTON ANTIBODIES
55
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
LW BLOOD GROUP SYSTEM: 016

56
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
28
2/3/2013

57
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

58
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
29
2/3/2013
LW ANTIBODIES
59
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
LW BLOOD GROUP SYSTEM: BIOLOGICAL ROLE

60
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
30
2/3/2013
CHIDO/RODGERS BGS: 017

61
contains 10 antigens Most Ch/Rg antigens are high-incidence antigens (>90%) Gene located on chromosome 6p21.3
CHIDO/RODGERS ANTIGENS
62
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
31
2/3/2013
CHIDO/RODGERS ANTIGENS
63
Chido/Rodgers Antibodies
64
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
32
2/3/2013
Chido/Rodgers: Biological Significance

65
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
GERBICH BLOOD GROUP SYSTEM:020

66
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
33
2/3/2013
Null Phenotypes in Gerbich

67
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
Gerbich Antigens
68
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)
34
2/3/2013
Gerbich Antibodies
69
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
Gerbich Antibodies
70
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
35
2/3/2013
BIOLOGICAL ROLE
71
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)
72
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
36
2/3/2013
Cromer Antigens
73
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

Null Phenotype (CROMER)

74
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)

37
2/3/2013
CROMER Antibodies
75
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
CROMER Antibodies
76
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
38
2/3/2013
77
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
Knops Antigens
78
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
39
2/3/2013
KN Antibodies
79
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
Biological Role
80
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)
40
2/3/2013
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
82
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
41
2/3/2013
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

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
42
2/3/2013
Indian Antibodies
85
IgG RBC-stimulated Reactive in IAT testing Anti-Inb causing HTR Neither antibodies causes HDN
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
43
2/3/2013
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
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
44
2/3/2013
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
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
45
2/3/2013
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

92
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
46
2/3/2013
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
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
47
2/3/2013
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

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
48
2/3/2013
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
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
49
2/3/2013
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
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
50
2/3/2013
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
BLOOD GROUP COLLECTIONS
102
51
2/3/2013
High Incidence Antigens (901 Series)
103
Low-Incidence Antigens (700 Series)
104
52
2/3/2013
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!
UPDATES
106
Lewis System Chromosome 19 6 Antigens

Lea, Leb Leab, LebH, ALeb, BLeb
53
2/3/2013
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
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.
54
2/3/2013
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
55

Blood Group Systems

Hochgeladen von

Dokumentinformationen

Originalbeschreibung:

Copyright

Verfügbare Formate

Dieses Dokument teilen

Dokument teilen oder einbetten

Freigabeoptionen

Stufen Sie dieses Dokument als nützlich ein?

Sind diese Inhalte unangemessen?

Copyright:

Verfügbare Formate

Blood Group Systems

Hochgeladen von

Copyright:

Verfügbare Formate

2/3/2013

DUFFY BLOOD GROUP SYSTEM (008)

DUFFY BLOOD GROUP SYSTEM

DUFFY BLOOD GROUP SYSTEM

DUFFY ANTIGENS: Fya & Fyb

DUFFY ANTIGENS: Fya & Fyb

BIOLOGICAL ROLE: Duffy BGS

BIOLOGICAL ROLE: Duffy BGS

KIDD BLOOD GROUP SYSTEM

GENE: (JK, SLC14A1, UT-B)

Null Phenotype: Jk(ab)

KIDD BLOOD GROUP ANTIGENS

KIDD ANTIBODIES: Anti-Jka and Anti-Jkb

KIDD ANTIBODIES: Anti-Jka and Anti-Jkb

Many examples bind complement

not store well

KIDD Blood group system

DISEASE ASSOCIATIONS: With Jkb-like specificity:

Jknull individuals exhibit a slightly decreased capacity to concentrate urine

DIEGO BLOOD GROUP SYSTEM: 010

The most interesting Diego antigen, however, is Wrb

an integral part of the RBC membrane

CARTWRIGHT (Yt) Blood Group

CARTWRIGHT (Yt) ANTIGENS

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

of all glycophosphoinositol (GPI)-linked glycoproteins

Anti-Yta and Ytb are usually clinically benign

Biological Role: CARTWRIGHT

XG BLOOD GROUP SYTEM:012

XG BLOOD GROUP Antibodies

SCIANNA BLOOD GROUP SYSTEM : 013

SCIANNA BLOOD GROUP SYSTEM: ANTIBODIES

naturally occurring anti-Sc2 antibodies are known

Biological Role: SCIANNA

DOMBROCK BLOOD GROUP SYSTEM: 014

by 67% and 82% of white donors, respectively

DOMBROCK : Null Phenotype

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

Dombrock can be destroyed by:

COLTON BLOOD GROUP SYSTEM: 015

COLTON BLOOD GROUP SYSTEM: 015

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

as the red cell water transporter

antigens are products of a gene on chromosome 7

can be clinically significant

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

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

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

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

LW BLOOD GROUP SYSTEM: 016

LW BLOOD GROUP SYSTEM: 016

LW BLOOD GROUP SYSTEM: 016

Antigens are destroyed by sulfhydryl reagents and pronase

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

ICAM4 gene resides on chromosome 19p13

LW BLOOD GROUP SYSTEM: BIOLOGICAL ROLE

CHIDO/RODGERS BGS: 017

Chido antigens are on C4B and Rodgers antigens are on C4A

Chido/Rodgers: Biological Significance

GERBICH BLOOD GROUP SYSTEM:020

Null Phenotypes in Gerbich

Antibodies to the low-incidence antigens: anti-Wb, anti-Lsa, anti-Ana, and anti-Dha

IgG with an IgM component Not binding complement