Blood groups Flashcards
What drives hyperacute solid organ rejection?
Major ABO incompatibility resulting in thrombosis due to recipient anti-A/anti-B.
When is ABO detectable in development? When do the antibodies form?
Detectable at 5wks in diminished quantity (due to non-branching i chains). Antibodies develop at 3-6mo and increase until 5-10yrs.
What factors can drive higher anti-ABO titers in donors?
Multiparity, probiotic use
What is the difference between the A and B glycosyltransferases?
Only 3 amino acids differ. Hybrids between the two may have specificity for both sugars (cis-AB)
What is the O glycosyltransferase?
Actually loss of the A/B sugar transferase, usually due to frameshift or nonsense mutations.
How does A1 subgroup differ from A2 subgroup?
A1 has about 5x as much A antigen, also qualitative differences probably reflecting contributions to T3 and T4 chains.
What is B(A) phenotype?
An autosomal dominant trait that results in weak expression of A antigen in predominantly group B patients (ie, a B transferase that can transfer NAcGlc)
What causes acquired B? How can it be avoided from the lab’s perspective?
Bacterial deacetylation of GlcNAc to Glc. Can be affected by reagent pH and specific anti-B clones (ES-4), so avoid those and use acidified reagent.
What is the order of blood groups by decreasing H antigen expression?
O > A2 > B > A2B > A1 > A1B
How do Bombay phenotype patients present on lab workup? What causes it? Associations?
“O” patients that show panagglutination to reagent O cells and no Ulex agglutination. Caused by loss of both FUT1 (missense) and FUT2 (deletion). Associated with leukocyte adhesion deficiency.
What is para-bombay phenotype?
Expression of FUT2 but not FUT1 (only secreted H antigen). Some soluble H antigen can adsorb onto red cells, resulting in “Ah/Bh/ABh/Oh” phenotype, but they still don’t really react with Ulex and can express anti-H.
Where is anti-H seen?
In Bombay, para-bombay, but also randomly in healthy A1 and A1B people (not significant in these cases)
On what chains are Lewis antigens expressed?
Type 1 chains
Who may express both Lewis A and B antigens?
Infants (during development, secretor enzyme is weak) and asians (FUT2 variant “SeW”).
When does lewis antigen expression mature?
5-6 years of age.
What condition is associated with Le(a-b-) phenotype in African American patients?
Leukocyte adhesion deficiency. (E and P selectins bind CD15, or sialyl-lewis X)
What is the difference between I and i?
The degree of branching in the type 2 chain backbone sugar; I is branched, i isn’t. I is adult, i is pediatric (mostly).
i(adult)
Results from autosomal recessive GCNT2 mutations, mostly in asians. Associated with HEMPAS, congenital dyserythropoietic anemia, and cataracts (not in all forms).
Anti-I
Auto: Strong cold-reacting IgM
Allo: Only seen in i(adult), insignificant
Cold agglutinin syndrome
Autoanti-I/i seen in cancer or mycoplasma infection. Can cause hemolysis if thermal amplitude is broad.
How are P, Pk, and P1 made?
Pk is synthesized from lactosylceramide.
P (globoside) is synthesized from Pk
P1 is synthesized from Paragloboside.
How many P phenotypes are there? What are they?
P1 (common) - P+/Pk+u/P1+ P2 (uncommon) - P+/Pk+u/P1- p (rare) - No antigens P1k (rare) - P-/Pk+/P1+ P2k (rare) - P-/Pk+/P1-
What anti-P group antibodies are significant?
Anti-PP1Pk (seen in p phenotype).
Anti-P (allo in Pk, auto in PCH)
What is FORS?
A single low-prevalence antigen attached to P antigen which resembles A (may react with anti-A). Encoded by GBGT1 (Forssman synthase).
Racial distribution of P phenotypes
P1: Black > White > Asian
P2: Asian > White > Black
All others rare
What are the relationship of RHD and RHCE?
They have 97% structural homology and are inverted from one another. Likely arose from a duplicationh event.
What are the different mechanisms of RHD negative phenotype?
White: Deletion of whole gene from nonsister chromatic exchange.
Black: Nonfunctional pseudogene with early stop codon (psi)
Asian: Silencing gene mutation or Del
What is the Ceppellini effect?
Less D antigen is expressed when C is expressed.
Weak D
Abnormal localization of D because of a SNP resulting in less surface D. Some may form anti-D.
Partial D
Partial replacement of RHD with RHCE»_space; loss of some D epitopes. Apparently D+ patient can develop anti-D.
Del
Extremely low D expression, only detectible by adsorption/elution.
Elevated D
Replacement of RHCE by RHD.
What percentage of D-negative patience will alloimmunize following exposure?
30%
G antigen
Epitope common to C and D, antibodies are reactive with both and must be eluted with D-/C+ and D+/C-
Altered C
Whites: Expression of Cw (Gln41Arg) or Cx (Ala36Thr)
Blacks: Novel antigens JAKH (122) and JAL (114), but also V-VS+ phenotype
Partial e
Seen in *ce alleles in black pateince. Loss of high prevalence hr(b), hr(s).
Compound antigens
Epitopes resulting from specific haplotypes... f - ce Rhi - Ce Rh22 - CE Rh27 - cE
What are the utilities for Rh genotyping?
To check zygosity
Fetal testing
Resolves typing discrepancies
What is RHAG?
A gene on chromosome 6 with limited homology with RHD and RHCE. Plays a role in stabilizing Rh proteins.
Rh null phenotype
Rhnull (“regulator”) phenotype causes loss of all RH antigens. Associated with stomatocytosis nad mild anemia.
What anti-Rh antibody other than D most often causes HDFN?
Anti-c
What are some causes of false-positive Rh typing?
Agglutinins, rouleaux, contamination/wrong reagent, gel/diluent antibody.
What are some causes of false-negative Rh typing?
Bad suspension, wrong reagent, failure to detect weak D (on IS), strongly positive DAT blocking antigen sites
What proteins comprise the Rh complex?
RHD, RHCE, RHAG, CD47, protein 4-2, ankyrin 3, duffy, glycophorins B & C
What is the main structural difference between glycophorins A and B? How do they react to enzymes?
Glycophorin A is N-glycosylated, Glycophorin B isn’t. Both are degraded by ficin/papin. Glycophorin A is trypsin sensitive, while glycophorin B is chymotrypsin sensitive.
What antigens result from the “B-A-B” hybrid glycophorin?
Mur, MINY, Hil, Mi(a)
Is there any racial distribution of MNS antigens and antibodies?
Not for M/N, but S is more common in whites, so blacks more often express anti-S as well as anti-S-s-U-.
In what tissues are glycophorins A & B expressed? Are they pathogenic binding sites?
Glycophorin A is restricted to erythroid lineages, but glycophorin B is not. Both are binding receptors for Plasmodium Falciparum
What is the structure and function of the Lutheran blood group?
Laminin (but with no known ligand).
How is Lutheran blood group affected by enzyme treatment?
Resistant to ficin/papin, but degraded by trypsin/chymotrypsin.
Summarize Lutheran antibodies.
Usually IgG but insignificant. Watch for LuA, LuB, and Lu3 (from null homozygotes). Classically causes MIXED FIELD AGGLUTINATION
In(Lu)
Asymptomatic phenotype resulting from heterozygous EKLF/KLF1 muation, with reduced expression of Lu, P1, and i.
What is the antigen prevalence of KEL1 in different races?
9% in whites
2% in blacks
<1% in asians
Kp(a) (KEL3)
Found in 2% of whites, this antigen causes reduced expression of all other Kell antigens.
Js(a)
Found in 20% of black patients, vanishingly rare in all other races.
What are the features of HDFN due to anti-K?
Less amniotic and postnatal hyperbilirubinemia; presents instead as erythrosuppression with decreased reticulocytes.
Ko
Kell null phenotype; Kx is preserved but all other antigens are lost. Patients are asymptomatic but can develop an anti-Ku that reacts to all Kell antigens other than Kx.
Kmod
Reduced but not absent Kell antigen expression, can manifest Anti-Ku-like antibody.
Expression of what non-Kell antigens can express Kell expression?
Gerbich (absence of Ge2/Ge3 lowers Kell expression)
McLeod phenotype
Kx deletion, associated with muscular and neural dystrophies and acanthocytosis. May be associated with CGD (these patients also produce anti-Kx and anti-Km and are nearly impossible to transfuse).
What is the structure and function of Duffy?
Chemokine receptor (scavenger?) that is widely expressed.
What is the basis of duffy null phenotype in Africans?
Homozygous GATA promoter binding site mutation of FY*B abrogates expression in erythrocytes.
What is the basis of duffy null phenotype in whites?
True duffy null due to inactivating mutations. These patients can produce anti-Fy3, anti-Fy5.
What is the basis of duffy null phenotype in pacific islanders and in Brazil?
Homozygous GATA promoter binding site mutation of FY*A abrogates expression in erythrocytes.
What is the binding receptor for plasmodium vivax?
Duffy
What are the three relevant Kidd antigens?
JkA (more common in blacks than B)
JkB
Jk3 (antibodies seen in null patients)
In(Jk)
Seen in some Japanese patients due to presence of an inhibitor. Very weak kidd expression.
Summarize Kidd antibodies.
Half can bind complement, as they are often mixtures of IgG and IgM. Often weak and anamnestic on pre-transfusion testing. Rarely causes HDFN.
Kidd null phenotype
Cells resist lysis in 2M urea
Patients can express anti-Jk3
What is the diego antigen?
Band 3 (SLCA1), a major cytoskeletal protein that complexes with ankyrin, protein 4.1/4.2; also an ion transporter and gas channel.
Di(a)
Low-prevalence diego antigen antithetical to Di(b). Seen in asians and native americans. Antibodies cause HDFN, but not HTR.
Wr(a)
Low-prevalence diego antigen antithetical to Wr(b). Common antibody that can cause severe HTRs and HDFN.
Yt(a) and Yt(b)
Yt(a) high prevalence and Yt(b) low prevalence antigens of Cartwright system. Acetylcholinesterase.
What is unique about the XG blood group system?
Despite being on the X chromosome, this gene does not undergo lyonization.
What are the two antigens of the XG blood group system?
Xg(a): Found on 66% of males and 89% of females.
XG2 (CD99): Also expressed on Y chromosomes.
Scianna blood group system
“ERMAP”, a pretty insignificant blood group system with 7 (“sceven”) antigens
What are the significant antigens of the Dombrock blood group system?
Do(a) < Do(b).
>Gy(a) in rare dombrock-null patients.
Antibodies here cause HTR but not HDFN.
What are the significant antigens of the Colton blood group system?
Co(a)»_space; Co(b)
>Co3 in rare Colton-null patients.
Antibodies can cause HTR but not HDFN.
What are the significant minor blood group systems?
Dombrock, Colton, VEL, Diego
In what contexts can anti-Lw antibodies be seen?
Lw(a) and Lw(b) homozygotes, rare LW-null and Rh-null patients (LW expression depends on Rh).
How can anti-Lw antibodies be distinguished from Anti-D?
LW is degraded by DTT.
Chido/Rodgers blood group
C4D.
9 antigens, insignificant.
What abnormal red cell morphology can be seen in Gerbich-null patients? What antibodies do they form?
Elliptocytes. Can form anti-Ge2, -Ge3, -Ge4.
What is the Gerbich blood group system?
Glycophorins C and D
Receptor for plasmodium falciparum (also true of glycphorins A and B).
Cromer blood group system
CD55 (DAF)
Falciparum binding receptor. Insignificant in blood banking.
(absence does not result in PNH, need to lose CD59 too)
Knops blood group system
CD35 (complement receptor)
Insignificant blood group system, falciparum binding receptor.
Indian blood group
In(a)»_space; In(b). In(Lu) cells useful for testing for >AnWj?
OK blood group
CD147
3 antigens: All high prevalence, all insignificant.
Raph blood group
CD151 (absence a/w deafness and renal failure)
Insignificant.
JMH blood group
CD108; loss of expression with age causes accumulation of auto-anti-JMH. Insignificant.
GIL blood group
AQP3. Insignificant.
RHAG blood group
4 antigens (Duclos, DSLK, Ola, RHAG4). Abnormalities result in Rh-regulator phenotype.
FORS blood group
Terminal sugar on GLOBOSIDE (P). Encoded by GBGT1. Low frequency.
JR blood group
One antigen, associated with drug resistance. Negative in Japanese.
LAN blood group
High prevalence, insignificant
VEL blood group
High prevalence, significant (severe HTR)
CD59
One case report, insignificant.
Augustine
ENT1/At(a), nulls have bone malformations. Insignificant.
AnWj
Haemophilus influenzae receptor, carried on CD44/UIn
What are the Bg antigens?
HLA antigens. Some have known specificities:
Bg(a) = HLA-B7
Bg(b) = HLA-B17
Bg(c) = HLA-A28
What erythroid phenotypes are caused by KLF1 mutations?
Heterozygosity in KLF1 causes In(Lu) phenotype, resulting in lowered expression of antigens on CD44 (In, AnWj) and P1. Also results in abnormal beta-globin expression resulting in persistence of fetal hemoglobin.Some mutations cause a severe congenital dyserythropoietic anemia.
Where is the Landsteiner-Wiener antigen located? In what settings can LW-null phenotypes be seen?
It is associated with the Rh system; expression of LW is higher in D+ patients. Some cases of LW-null phenotype occur with Rh-null phenotype.
How can anti-D be distinguished from anti-LW?
Use DTT-treated cells (degrades LW antigen, but not D). Or, just use molecular testing.
How many A antigens per RBC are seen in A1 subgroup? A2?
A1: About 10^6 (one million).
A2: About 2 x 10^5 (200,000).
What non-ABO antibodies may be naturally occurring?
> E
Lu(a)
Di(a)
M. >N (mostly IgM)
What is the most common autoantibody specificity other than broad?
Anti-E
What is the human RBC binding site of C3b?
Glycophorin B (may not be only binding site)
