Other Blood Groups Flashcards
What is the structure of CO antigens?
Multipass - pass membrane 7x
located on aquaporin-1 (AQP1)
Also called CHIP-28 channel forming integral protein
It is a water channel that is responsible for 80% of the water that is reabsorbed in the kidneys
What antigens are present in Colton (CO) BGS?
Coa and Cob are co dominant (Coa = High)
Co3 and Co4 are high freq. present when colton antigens are present >0.01% is Co(a-b-)
What are characteristics of the Colton antigens?
Present on cord cells = mild/severe HDFN
Not destroyed by DTT or enzymes
Poor immunogens - few Colton antibodies seen
Weak typing seen in In(Lu) phenotype
What is Co null?
Co(a-b-) Caused by silencing of CO gene Cells are Co:(-a,-b,-4,-5) Co-3 = no aquaporin and may have serious electrolyte and metabolic disorder when dehydrated Co-4 = have functional aquaporin
What are the characteristics of Co antibodies?
IgG; reacts are IAT Have been implicated in HTR and HDFN May bind complement Cob - found w/ other antibodies (XM comp; 8% Cob+) Coa require rare antigen neg units
How do you antigen type for Coa?
No antisera available.
Molecular typing can be preformed
What chromosome is Xg located on?
Chromosome X
Xga and CD99 escape x inactivation
What antigens are present in Xg BGS?
Xg1 = Xga on RBC’s
Xg2 = CD99 a high prevelance antigen that is also present on fibroblast and lymph nodes
Phenotype is either Xga- or Xga+
How is Xga inhierted?
Xga is X linked dominate - occurs in females more often
Males will be hemizygous if inherit from mother and will pass Xga to all daughters
What % of females and males are Xga positive?
66% of males are Xga positive
90% of females are Xga positive
What are the characteristics of Xga antigen
Sensitive to enzymes
Resistant to DTT
Poor immunogen
What are the characteristics of anti-Xga?
IgG reacts at IAT
immune stimulated
May see MF due to low density of antigens on the RBC’s
What is lyonization?
In females, a random X chromosome is inactivated early in somatic cell developement.
Once a x chromosome is inactivated all cells from that clonal will have the same X inactivation
Xga escapes lyonization= no dual population of RBC
What is the gene name for Diego BGS?
DI or SCL4A1
What is the gene product for DI?
Band 3 (anion exchanger 1)
What is structure/function of Diego antigens?
Diego is a multipass glycoprotein on band 3
Makes up 20% of membrane protein
Band 3 transports anions of bicarb and Chloride across the cell membrane and allow CO2 to enter
Band 3 is achnored the membrane by ankyrin and protein 4.2
What disease is associated with lack of band 3?
Mutation in band 3 results in SE Asian ovalucyctosis, hereditary spheocyctosis, and some acantocytosis
What are the High frequency DI antigens?
Dib, Wrb, and DISK
Di(a-b+) = most common
What are the characteristics of Dia antigens?
Present on Cord cells
Can cause HDFN
Resistant to Ficin and DTT
What is frequency of Dia?
Very low freq. in Caucasians
Present in Mongolian populations
50% of S American Indians
12% of Asians
What are the characteristics of DI antibodies?
IgG1 and IgG3
Can cause HDFN
Immune stimulated (one naturally occur. anti-Dia)
What is prevelance of Wra and Wrb antigens?
Wra is low frequency
Wrb is 100% frequency
Where is Wrb antigen located on?
It is on AE-1 in close association with GPA
GPA is required for Wrb expression
GPA neg and MkMk individuals lack Wrb
What are the characteristics of Wra antibodies?
IgG and IgM
Can be naturally occur. Found in 2% of un-transfused males and seen in pregnant women
Often seen with other antibodies or warm auto’s
Relatively common
Can cause HTR and HDFN
What are the characteristics of Wrb antibodies?
Allo anti-Wrb is rare
Made by Ena- M-N- individuals
Auto anti-Wrb can occur and cause hemolysis
What is the former name of the YT BGS?
Cartwright
it is YT and not Yt
What is the gene name and chromosome location of YT?
Located on Chromosome 7
Gene name is YT or ACHE
What is the structure of YT antigens?
On a glycophosphatidylinositol (GPI) linked glycoprotein acetylcholinesterase
What is the function of AChE?
AChE plays an essential part in neurotransmission.
What diseases are associated with AChE?
RBC’s from PNH III are deficient in AChE
AChE is reduced in MDS and some SLE
What antigens are in the YT BGS?
Yta and Ytb
Yta is high frequency (0.3% negative)
8% are Ytb positive
NO Yt(a-b-) found to date
What antigens are linked to the RBC membrane by aglycophosphatidylinositol (GPI) linked glycoprotein?
YT Dombrock Cromer JMH EMM
Can anti-Yta or Ytb cause HDFN?
Yta is not developed at birth. It is weak or negative on cord cells so doesn’t cause HDFN.
Ytb is present at birth
Are YT antigens sensitive to enzymes or DTT?
Yta and Ytb are sensitive to ficin and DTT but resistant to trypsin
What are the characteristics of anti-Yta?
IgG1 and IgG4
MOSTLY BENIGN, but some cause HTR
If anti-Yta is IgG4 it will not cause hemolysis because macrophages do not have receptors for IgG4
Weak reactive antibody destroyed by enzymes and weakend with DTT
How can you determine if patients anti-Yta is clinically significant?
Monocyte monolayer assay CR51 survival - invassive procedure IgG subclass assay consider giving Yta positive blood in an emergency 50% are not clinically significant
What are the characteristics of anti-Ytb?
IgG
Rare antibody, reported in patients who had multiple transfusions (Ytb is low present in 8% individuals)
Not considered clinically significant or known to cause HTR/HDFN.
What is the gene name and gene product for scianna?
SC is gene name
Product is Sc glycoprotein ERMAP (erythroid membrane associated glycoprotein)
What antigens are present in the SC BGS?
7 antigens that are high freq except SC2 and SC4
SC3 is present when either Sc1 or Sc2 is present
SC4 = Radin
SC5 = STAR
SC6 = SCER
SC7= SCAN
Are the SC antigens resistant to enzymes or DTT?
SC antigens are resistant to enzymes and varied with DTT
What is the frequency of Sc1,-2?
99%
What is the frequency of SC-1,2?
Very rare
What is the frequency of SC-1,-2,-3 (Null)
Very rare
Cluster of people found in Papa New Guinea
- can make anti-SC3 that reacts with all SC1 or SC2 positive cells
What are the characteristics of SC antibodies?
SC antibodies are rare
IgG but generally don’t cause HTR or HDFN
Anti-SC2 and SC4 may cause mild HDFN
Anti-SC3 made by Sc null may cause HTR
What is the gene name and gene product for Dombrock BGS?
Gene is DO
Gene product is Dombrock glycoprotein
What is the structure of Dombrock
glycophosphatidylinositol (GPI) linked glycoprotein
What is the disease associated with Dombrock?
Dombrock is absent from PNH III cells
What are the Dombrock high frequency antigen?
DO3 = Gya DO4 = Hy DO5 = Joa DO6 = DOYA DO7 = DOMR DO8 = DOLG
What are the frequencies of Doa and Dob antigens in whites?
Doa = 67% are positive
Dob = 82% are positive
(similar to Fya/Fyb)
What is the Gya negative phenotype?
True DO null NO Dombrock antigens Extremely rare Found in eastern Europeans and Japanese Anti-Gya found in whites
What is the Hy negative phenotype?
Anti-Hy Found in blacks
Weak Dob and Gya.
Negative Doa, Hy, and Joa
What is the Joa negative phenotype?
Unusual; Anti-Joa found in blacks
Negative Joa
Weak Doa, Weak/neg Dob, Weak Hy, and Weak Gya
What are the characteristcs of DO antigens?
Resistant to ficin and papain
Destroyed by DTT and trypsin
DOa and Dob developed at birth
Poor immunogen
What are characteristics of Do antibodies?
IgG and immune stimulated
Do not bind complement
Generally do not cause HDFN
Poor immunogens - antibodies are uncommon
Anti-Doa and Dob have caused HTR
Found with other antibodies. Explains unexpected reactions.
What is the gene name and product of Gerbich antigens?
Gene name is GE or GYPC
Gene product is GPC and GPD
What is the function of GPC and GPD?
GPC and GPD interact with protein band 4.1 and helps maintain red cell cell shape
What is the effect of decreased protein band 4.1?
Decreased GPC and GPD
Causes hereditary elliptocytosis
GE antigens are a receptor for what?
Plasmodium falciparum and influenza A/B
What are the high freq GE antigens?
Ge2, Ge3, Ge4, GEPL, GEAT, GETI
Ge1 is obsolete
What are the characteristics of GE antigens?
present on cord cells
Most common phenotype = Ge 2, 3, 4 = 99.9%
Where are GE negative phenotypes found?
Papua New Guinea
GE gene is silenced
What is the Yus phenotype?
GE: -2, 3, 4 GPC is abnormal GPD is absent can make anti-Ge2 Kell typing is normal
What is Gerbich phenotype?
GE: -2, -3, 4 GPC is abnormal GPD is absent can make anti-Ge2 and anti-Ge3 Kell typing is weak Common in Melanesian's
What is the Leach phenotype?
GE: -2, -3, -4 True null GPC and GPD is absent Elliptocytes present Can make anti-Ge2, -Ge3, and Ge4 Kell typing is weak
What are the characteristics of Ge antibodies?
IgG; may have IgM Immune stimulated; naturally occurring sometimes NOT clinically significant Does not bind C' Anti-Ge2 and Anti-Ge3 reported in AIHA
Does anti-Ge3 cause HDFN?
Yes, suppresses RBC production similar to Kell antibodies
How do differentiate anti-Ge2, -Ge3, and -Ge4
All are sensitive to trypsin and papain
Except Ge3 is resistant to Papain
What is the structure of Cromer antigens?
Antigens located on DAF, a glycoprotein (CD55), which is anchored to cell by GPI linked
What is the function of DAF (CD55)?
Functions in complement regulation
accelerates decay of C3 and C5
C3 convertase is inhibited and cascade stops
What disease is associated with DAF?
PNH - Paroxysmal nocturnal hemogloburia
No GPI = NO CD55 or CD59
Complement not regulated = hemolysis
Caused by rare clonal defect
What are the low and high freq cromer antigens?
Cra, Tca, Dra, IFC
Blacks = Tc(a-b+c-) Tcb = low
Caucasian = Tc(a-b-c+) Tbc = low
Where are Cromer antigens located?
Serum/plasma, urine, platelets, WBC, and placenta tissue
Can be inhibited by serum or urine and adsorbed by platelets
What are characteristics of cromer antigens?
Depressed during pregnancy
Poorly expressed on cord cells (No HDFN)
Resistant to enzymes
Weakend by DTT and chymotrypsin
What are the characteristics of Cromer antibodies?
IgG1; reacts at IAT Immune stimulated Inhibited by serum or concentrated Urine Antibodies are rare Can be absorbed by platelets
Are CROM antibodies clinically significant?
Generally not clinically significant
No firm evidence of HTR
HDFN unlikely because antigen is present on placental tissue and poorly expressed on cord cells
What is the function of CD59?
A complement regulatory glycoprotein that is GPI linked and functions by binding to C9 to prevent MAC formation
What is Dra negative phenotype?
Dra is high freq. CROM5 antigen
Dr(a-) have weak expression of CROM antigens
What is the Inab phenotype?
CROM Null
IFC negative = CR7 negative
RBC’s lack CROM and DAF
Found in Japan
Can make anti-IFC that reacts with all cells
CD59 is still present to regulate C’ so hemolysis doesnt occur
What testing confirms PNH?
Historically= Sucrose lysis test and Ham’s acid test
Now flow cytometry for CD55 and CD59
What is the gene name and gene product for the Indian BGS?
Gene name IN
Codes for glycoprotein CD44
Leukocyte adhesion and homing receptor
Involve in T and B cell activation
What is the most common IN phenotype?
In(a-b+) Inb high freq
In(a+b+) found in Indians and Iranians/Arabs
What the characteristics of IN antigen?
Destroyed by Ficin, papain, and DTT
Cord cells have weak antigens - no HDFN
What are the characteristics of anti-Ina and anti-Inb?
Very immunogenic - many IN antibodies reported
Anti-Ina is rare (low freq)
Anti-Inb more common in Arabs, East Indians, and Asians
What is the IN null phenotype?
In(a-b-) causes by a SNP of a seperate gene, KLF1, that encodes for Kruppel-like factor (KLF1)
The SNP also causes In(Lu) - Lu(a-b-)
What is the relationship of IN, In(Lu), and AnWj?
The In(Lu) phenotype has reduced levels of IN(CD44) and AnWj. Adsorption/elution required. Other tissues have normal antigen expression
What is AnWj?
High freq. part of 901 series
Antigen is on CD44 and may be moved to IN BGS
Antigen varies in strength in different individuals
Unlike Ina and Inb, AnWj is not affected by enzymes
Can cause HTR; In(Lu) cells should be transfused
Not present on cord cells so doesn’t cause HDFN
What BGS is Sda part of?
High freg antigen in the 901 series
What is the gene and gene product of Sda?
Gene encodes for B(1-4) N-acetyl-galactosyltransferase
Adds a GalNac to 4th sugar of GPA (Like group A)
What is the frequency of Sda?
91% will type Sda positive 96% will have Sda in urine - Tamm horsefall glycoprotein 4% are truly Sda negative Sda expression is variable
Where are Sda antigens present in an Adult?
Urine, RRC’s, Plasma, and saliva
What happens to Sda antigen during pregnancy?
Similar to Lewis antigens Sda antigens are decreased during pregnancy
Sda still found in urine and saliva
Is Sda present in newborns?
Sda is not present on Newborn RBC’s
Sda is present in urine and saliva
What are the characteristics of anti-Sda?
Present in only true Sda negative people
-seen naturally occurring in 50% of Sda- people
Not clinically significant
Usually IgM but can be IgG
Can fix complement
MF agglutination and refractile appearance
Neutralized by urine
How is urine neutralization preformed?
Pool 6 samples of human urine
Make a PBS control for dilution control
Combine equal parts of urine and PBS Ct with serum and incubate 30 min
Test 4 drops of neutralized serum with cells that were MF positive. If not agglutination with neutralized sample but still agglutination with PBS CT then anti-Sda was neutralized.
How do you transfuse people with anti-Sda?
XM compatible
What is CAD?
Rare form of super Sda inherited by autosomal dominance; polyagglutination
anti-CAD is present in normal healthy people so CAD positive cells would react with all normal plasma.
CAD cells will react with dolichus biflorus and salvia horminum
What antibodies are grouped in the HTLA-like category?
Chido/rogers JHM Kn, McC, Sla, Vil (KN) Cost Gya, hy, Joa (DO) YT
What are general characteristics of HTLA-like antibodies?
IgG with weak agglutination and high titer
Do not bind complement
Not enhanced by LISS; react best with 60 min Saline
Variable reactions that are difficult to reproduce
Reactions strong with fresh cells; XM compatible with older units
What are the characteristics of Ch/Rg antigens?
soluble antigen in the plasma that’s adsorbed onto the RBC membrane
Rogers is on C4A (acidic isoform)
Chido is on C4B (Basic isoform)
C4 is cleaved and C4d contains Ch/Rg and is adsorbed onto the membrane
What disease is associated with Ch/Rg antigens?
Rg negative is likely to develop SLE = 2% of healthy donors
Ch negative is likely to develop bacterial meningitis
What causes a Rg negative phenotype?
Gene deletion and it associated with HLA-A1, B8, DR3.
Small deletion in the C4A gene results in no Rg antigens and individuals can make Anti-Rg
10-15% of SLE patients are Rg negative
How do identify Ch/Rg antibodies?
Non-reactive with enzyme treated cells
Resistant to DTT
neutralized with human plasma (Use pooled)
Anti-Rg can show partial inhibition
Will react strongly with C4d coated
Can neutralize antibody in patient by transfusing FFP
What is JMH?
John Molton Hagen Anti-JMH found in males over 60 Often found in JMH+ people with DAT+ due to variants Does not cause HTR or HDFN Destroyed by Ficin
Where are Knops antigens located on?
Complement Receptor 1
Can be neutralized with CR1
What is the Helgeson phenotype?
Low levels of KN antigen Kn(a-b-), McC(a-), Sl(a-), Yk(a-)
Lacks CR1 that on RBC’s and PLT’s binds to immune complexes and transports them to the liver
Acquired decreased CR1 levels seen in SLE, AIHA, PNH, HIV and other immune diseases
What are the Knops antigens (KN)?
Kn(a+b-)
McCa+ (McCb+ in 45% of blacks)
Sl1 or Sla - Sl1= in 40% Blacks
Yka+ (High)
What is Sl1 or Sla (KN4)?
98% of whites are positive
60% of blacks are positive = Anti-Sla seen in blacks
Can be confused with anti-Fy
What antigens are in the COST collection?
Csa = 98% of people are positive
Csb = 34% of people are positive
antibodies are rare
What is the relationship of Csa and Yka?
Yka is part of Knops system and carried on CR1
Csa is part of Cost collection and not carried on CR1 however Csa negative people are often Yka negative for an unknown reason
Both are present in 98% of individuals
What techniques help ID HTLA-Like antibodies?
Plasma inhibition for Ch/Rg Ficin destroys Ch/Rg and JMH C4d coated cells react strongly with anti-Ch/Rg sCR1 for Knops Trypsin destroys Knops DTT destroys Knops and Dombrock
What are characteristics of HLTA-like antibodies?
Look pan-reactive with weak reactions
react better with fresh cells; try older RBC’s for XM
Have a very high titer with consistent weak reactions (<32)
Don’t absorb/elute or prewarm away
Not clinically sig. just R/O Allo’s
What are Bg antigens?
Bg antigens are remnants of HLA antigens on RBC’s
They vary in strength in different people and can type positive one time and same person can type negative a different time
Many people don’t express Bg antigens on RBC even if corresponding HLA is present
What HLA is Bga?
HLA B7
What HLA is Bgb?
HLA B17
What HLA is Bgc?
HLA A28
How do identify anti-Bg antibodies?
Reactivity does not match pattern
Weak reactive in IAT
Found in multiply transfused on multiparous patients
Chloroquine treat cells or use platelets to neutralize antibodies
What is the 901 series?
Antigens that occur in 90% of the population and can’t be placed in BGS because the genes for them are not defined.
What is Jra?
High frequency antigen
Jra= found in Japanese so can make Anti-Jra
Does cause HTR and HDFN
What is LAN?
High frequency antigen that is very immunogenic
developed at birth
IgG; immune stimulated
Causes HTR and HDFN
What is VEL?
High frequency
VEL negative found in Norwegians and Swedes
VEL expression is variable due to variants
Anti-VEL is IgG, immune stimulated, can be hemolytic
Difficult to identify because varied reactions and adsorption/elution may not work
What is Ata?
Augustine or AUG
High frequency; Ata negative only seen in blacks
IgG; immune stimulate
Can cause HTR and HDFN
What is AnWj?
Part of 901 series carried on CD44 Suppressed by In(Lu) IgG and can cause HTR AnWj is receptor for H. influenzae
How do transfuse someone with anti-AnWj?
Rare donor registry and siblings
Do MMA testing
Consider transfusing In(Lu) phenotype because AnWj is weak or negative
What letter do most high freq antigens end in?
Most high in 'a' Except - Inb (IN) - Dib + Wrb (DI) - Lub - Kpb +Jsb (KEL) - Doa + Dob = polymorphic (Freq = Duffy)
What antigens are destroyed by Ficin/Papain and Trypsin?
Ch/Rg, XG, JMH, YT, Ge2, Ge4, IN, KN
Chido/Rogers eXiled JMH YeT Ge2+4 INcluded KNops
Duffy’s MNS’s were destroyed
What antigens are destroyed by DTT?
YT (Yta and Ytb) DO (Doa, Dob, Hy, Gya, Joa) CR (Cra, Tca, Dra, IFC) IN (Inb) LU JMH KN (Kna, McCa, Yka, Sla) LW KEL
Which antibodies can cause HTR’s?
CO (anti-Coa -CO3, -Co4) GE (anti-Ge2, -Ge3, Ge4) DI (anti-Dia, -Dib, -Wra, -Wrb) YT (anti-Yta; IgG4 determine Clin. Sig.) DO (anti-Doa, Dob, -Hy, -Gya, -Joa)
What antibodies are assoc. with Black ethnicity?
DO (anti-Hy, -Joa) AUG (anti-Ata) KN (anti-Sla or Sl1 looks like Fy3) anti-Jsb anti-U
What antibodies are assoc. with Japanese?
Junior (anti-Jra)
Inab = Cromer null (anti-IFC)
DO (anti-Gya)
What antibodies are assoc. with East Indians?
IN (anti-Inb)
What antibodies are assoc with Norwegians and Swedes?
anti-Vel
What antibodies are assoc. with melansians and Papua New Guinea?
Gerbich (Ge-2, -3, 4)
Scianna (Sc: -1, -2, -4)
What antibody is seen in Native American?
anti-Dib
Dia = marker for mongoloid, S. American indian, Asians
What are the GPI Linked proteins?
YT (Yta) DO (Doa/Dob, Gya, Hy, Joa) CROM (Cra, Tca, Dra, IFC) JMH EMM
