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Flashcards in Blood group antigens Deck (49)
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1

Carbohydrate antigens

  • ABO, Lewis, H, I, i, M, N, P1
  • affected by genes that encode enzymes (genes for protein antigens encode structural proteins)
  • glycosyltransferases catalyze transfer of saccharides to carbohydrate precursor chains
  • naturally occuring antibodies
  • antibodies are usually IgM
  • antibodies are usually reactive at room temperature
  • "agglutinating" antibodies (not coating antibodies)
  • react at IS

2

H antigen

  • made from type 1 (in serum and secretions) and type 2 (RBCs) carbohydrate chains by the enzyme products of the H (FUT1) and Se (FUT2) genes
  • in secretions and in plasma, type 1 chains are converted into H antigen (1H) by enzymatic reaction (fucosylation) of the Se gene product (Fut2)
  • on the surfaces of red cells, type 2 chains are converted to H antigen (2H) by fucosylation of H gene product (Fut1)

3

Lewis antigens

  • made from type 1 precursor by the enzyme product of Le (FUT3) gene
  • secreted Leb and Lec are receptors for Norwalk virus and H pylori
  • Lea is the Ca 19-9 epitope

4

A and B antigens

  • made from H antigen by the enzyme products of ABO gene
  • the A allele encodes N-acetyl-galactosaminyl transferase that adds N-acetyl galactosamine (NAG) to H, resulting in A antigen
  • the B allele encodes galactosyl transferase that adds D-galactose to H, resulting in B antigen
  • the O allele does not encode a functional enzyme, and group O red cells contain abundant unaltered H antigen

5

I and i antigens

  • epitopes within the ABH antigens
  • unbranched type 1 and type 2 oligosaccharides represent i antigen
  • branched type 1 and 2 oligosaccharides are I antigens
  • branched oligosaccharides (I) increase with age
  • in neonates and cord blood, i antigen predominates
  • in high red cell turnover states, a resurgence of i is sometimes observed
  • increased postnatal i antigen expression is characteristic of 
    • congenital dyserythropoietic anemia (CDA) type II
    • Blackfan-Diamond syndrome

6

Protein antigens

  • all the non-carbohydrate antigens, including Rh, Kidd, Kell, S, s, Duffy
  • antibodies acquired only after exposure to products containing antigen
  • antibodies are usually IgG
  • reactive at 37 degrees
  • "coating" not agglutinating antibodies
  • react at AHG phase

7

O blood group produce what antibodies

  • produce naturally occuring anti A and anti B IgM
  • also produce IgG anti AB, which can cause ABO related hemolytic disease of newborn, which is typically mild

8

A blood group

  • results from AA or AO genotype 
  • 2 principal subgroups are A1 and A2
    • A1 cells express more A substance than A2 cells
    • 80% of blood group A people have A1 phenotype
    • A1 and A2 cells can be distinguished by strength of reaction with
      • anti A1 reagent from serum of blood group B people
      • Dolichos biflorus lectin, which has anti A1 activity
      • Ulex europaeus, which has anti H activity (reacts with A2 more than A1)
    • anti A1 can be found in serum of 5% of blood group A2 and 35% of A2B people
    • anti A1 is usually clinically insignificant

9

Bombay phenotype

  • very rare
  • has been seen in all populations
  • no H produced in blood
    • H produced in secretions if the Se gene is present
    • the H deficient secretor is often called the para-Bombay phenotype
  • these people produce a dangerous anti H

10

Type 1 and 2 oligosaccharides

  • Type 1 is unbound and found in secretions and in plasma
  • Type 2 is found only on red cell surface
  • unbranched type 1 and 2 oligosaccharides represent i antigen
  • branched type 1 and 2 oligosaccharides are I antigens

11

The H (FUT1) gene

- product

- relative amount of H antigen in different blood groups

  • encodes fucosyl transferase; substrate is type 2 precursor, product is H (2H)
  • when A gene product acts on H antigen, adding NAG, the A antigen results
  • when B gene product acts on H antigen, adding GAL, the B antigen results
  • relative amount of H antigen is as follows:
    • O  >> A2 > B > A2B >A1> A1B

12

The Se (FUT2) gene

  • encodes a fucosyl transferase: substrate is type 1 precursor, product is H (1H)
    • it produces the secretion and plasma equivalent of H substance and is responsible for appearance of A, B, and H substances in secretions
    • the Se gene is an amorph
    • 80% of population has the Se allele and are secretors
    • 20% are homozygous for se/se and are nonsecretors

13

The Le (FUT3) gene

- how are Lea and Leb made

 - Le(a-b+)

- expression on red cells

- expression changes with

- frequency of Le(a-b-) and Le(a+b+) 

Encodes a fucosyl transferase: substrate is type 1 precursor and 1H, product is Lea and Leb

  • Le fucosyl transferase adds fucose to type 1 precursor (in a different linkage than that catalyzed by Se) to make Lea 
  • the Le fucosyl transferase also can add fucose to 1H antigen to make Leb 
  • Thus
    • Lea can be made if Le is present
    • Leb is made only if both Se and Le are present
    • in Le (a-b+) people, a minute amount of Lea is still made, such that anti Lea antibodies do not form
    • though Lewis antigen is synthesized on free type 1 precursor substance, it becomes passively absorbed onto red cell surfaces
    • Le gene expression increases with age
      • Lewis type cannot be reliably determined until 2nd birthday
      • persons destined to be Le(a-b+) are as neonates Le(a-b-) then Le(a+b-) then Le(a+b+) and finally Le(a-b+)
    • Lewis antigen expression is decreased during pregnancy and the Le(a-b-) phenotype is transiently expressed
  • Le(a-b-) is present in blacks mainly

  • Le(a+b+) is very rare

14

Frequency of blood groups by ethnicity

  • O > A > B > AB and D+ in all groups
    • hispanic > black > white
  • A
    • white > black > hispanic
  • B
    • black > white and hispanic
  • AB 
    • white and black > hispanic

15

ABO antibodies

  • ABO antibodies are naturally occuring
    • detectable in infants by 3-6 months, but may not reach adult titers until 2 years
    • ABO incompatibility results in complement activation and brisk intravascular hemolysis
    • reactions can accompany transfusion of incompatible red cells (i.e., major incompatibility) and transfusion of incompatible plasma (minor incompatibility)

16

Lewis antibodies

  • Lewis antibodies are naturally occuring
  • found almost exclusively in Le(a-b-) people are commonly black
  • Le(a-b+) people do not make anti Lea antibodies
  • Lewis antibodies are nearly always IgM and insignificant 
  • during pregnancy, women can acquire Le(a-b-) phenotype, and they can develop LeLeb antibodies, which cannot harm the baby since fetal cells do not express Le antigens
  • rare significant Lewis antibody is anti Lea which are usually inconsequential because
    • transfused red cells shed their Lewis antigens and acquire the Lewis phenotype of the recipient
    • Lewis antibodies are quickly absorbed by free serum Lewis antigens

17

Anti I and Anti i antibodies

  • These are autoantibodies that are usually clinically insignificant
  • anti I Ab is associated with mycoplasma pneumoniae and lymphoma
  • anti i AB is associated with EBV 

18

P/GLOB antigens and phenotype

  • P1, P, and Pk are 3 different carbohydrate antigens
  • P1 is the only one of the above that belongs to the P blood group system
  • Pk and P do not belong to P, but instead belong to GLOB system
  • P antigen is the receptor for parvovirus B19 (fifth disease)
  • P antigen is target of antibodies in paroxysmal cold hemoglobinuria (PCH)
  • P group phenotypes are defined by reactivity with the antibodies anti P1, anti Pk, anti P, and anti PP1Pk
    • 80% of whites and 95% of blacks have the P1 phenotype (P1+, P+, Pk-, PP1Pk+)
  • the rare p phenotype is characterized by absence of P antigens 

19

Antibodies to P/GLOB blood groups

  • people with p phenotype make potent anti PP1Pk
    • anti PP1Pk is associated with delayed hemolytic transfusion reaction, HDFN, and first trimester spontaneous abortion
  • people with P2 may make anti P1
    • these are usually IgM, reactive at 4 degrees and not clinically significant
    • anti P1 can be agglutinated by 
      • hydatid cyst fluid
      • egg whites from pigeon eggs and turtledove eggs
    • anti P1 titers may be elevated in 
      • echinococcal infection (hydatid cyst)
      • bird handlers
  • anti P1 associated with
    • PCH
    • viral infections in kids
    • syphilis

20

Rh antigens and phenotypes

- genes

- chromosome #

- other associated proteins

- variants

- Rh null associated with

  • Rh antigens are polypeptide antigens encoded by closely linked gene loci RHD and RHCE
    • genes found on chromosome 1
    • products of RHD and RHCE genes form large complex on red cells
    • additional proteins associated with Rh complex, including LW and duffy (Fy)
    • C, D, and E are transmembrane proteins with multiple extracellular domains
    • multitude of epitopes and antigens
    • multitude of extracellular domains create possibility of "partial D" phenotype
  • Rh null associated with hereditary stomatocytosis (HS)

21

Most commone Rh- and Rh+ genotypes

  • Most common Rh- genotype is r/r (cde/cde)
    • 10-15% of blood donors are Rh-
    • highest incidence of Rh negativity is found in Basques (25%)
    • prevalence of r/r explains why recipients with anti c or anti e should not be given Rh- blood
    • the D- phenotype denotes absence of the D antigen (there is no d antigen)
    • Rh null people have no Rh antigens 
      • also have diminshed expression of LW, Fy5, S, s, and U
      • also have enhanced osmotic fragility, chronic hemolysis, and stomatocytosis
      • should only receive Rh null RBCs
        • if they receive Rh- RBCs, they will form anti total Rh antibody (anti Rh29)
  • Most common Rh+ genotypes are R1/R1 or R1/r in whites and R0/R0 or R0/r in blacks

22

Weak D

- what is it

- antibodies?

- how was it defined historically?

- mechanisms

- recipient status

  • Possess D antigen in smaller quantities
  • people with weak D do not form anti D antibody
  • transfusion of weak D cells into a D- person can cause sensitization, so these donors are labeled as D+
  • weak D defined historically by weak reactivity with anti D reagent, typified by the following reactions
    • negative at IS with anti D reagent
    • negative after 37 degrees incubation with anti D reagent
    • positive at AHG phase with anti D reagent
  • modern monoclonal anti D reagents can detect most weak D RBCs at IS such that weak D cells simply look like typical D+ cells
  • Mechanisms
    • most commonly results from mutations in the RHD gene
    • less commonly result from presence of Ce haplotype for RHCE gene on opposite chromosome, which exerts a dampening effect on D expression ("C in trans to D")
  • recipient not tested for weak D, only the donor is

23

Partial D

- mechanism

- transfusion of partial D cells

- pregnancy

- how is it identified

  • alteration in 1 of the epitope sequences of the D gene
    • results in D antigen with some, but not all, epitopes
    • people with partial D may form anti D antibody
    • transfusion of partial D cells into D- recipients can cause sensitization
    • partial D women are at risk for forming anti D antibodies with D+ pregnancies, for these reasons partial D woman recipient should be treated as D-
    • partial D is frequently identified because of an apparent discrepancy: the coexistence of D expression and anti D antibodies

24

Rh antibodies

- sensitization rate

- dosage

- enzymes

- clinical consequences

- anti E

- other antigens

  • IgG antibodies that are acquired through exposure
  • D antigen is most immunogenic of all non-ABO antigens 
  • when Rh+ blood is transfused to Rh- recipients in an emergency setting, the rate of sensitization is 20-30%
  • all Rh antibodies except anti D display dosage
  • all Rh antigens are enhanced by enzymes
  • Rh antibodies may result in hemolytic transfusion reactions and severe HDFN
  • If anti E is detected in serum, then the additional presence of anti c should be suspected
    • because most people with anti E have R1R1 phenotype (CDe/CDe), and have been likely transfused with R2 blood (cDE)
    • anti c may be undetectable but is a common cause of DHTR
  • G antigen is found on all D+ RBCs and most C+ RBCs
    • serologically anti G antibodies mimic anti D and anti C
    • multiple absorption/elution studies can distinguish anti G from anti D and anti C
    • in pregnant women, you must distinguish between anti D, anti C, and anti G since they will need RhIg to prevent formation of anti D
  • anti f (antibody against compound antigen ce) is most common alloantibody directed against compound Rh antigens
    • found primarily in DCe/DcE (R1R2)

25

Kidd antigens

- Jkb ethnicity

- Jk(a-b-) seen in what populations

- function of Kidd protein

- effect of enzymes

  • Jkb negative phenotype is twice as common in blacks than whites
  • Jk(a-b-) is rare, encountered in Finns and Polynesians
  • Kidd is a urea transport protein
    • Jk(a-b-) cells are resistant to hemolysis in 2M urea
    • this phenotype causes a mild urine concentrating defect
  • Enhanced by enzymes

26

Kidd antibodies

- level of detection

- dosage effect?

- clinical consequences

  • Difficult to detect (Tricky kidd)
  • tend to fall below threshold of detection over time
    • Kidd Ab diminish in stored blood (e.g., when sent to a reference lab)
    • historical kidd antibodies, despite absence of currently detectable antibody, is reason enough to give Kidd antigen negative blood
  • Kidd antibodies display dosage and may only react with homozygous cells
  • Dosage effect may result in a false negative crossmatch
  • Kidd antibodies most often react only at the AHG phase
  • most common cause of DHTR
  • Rarely causes HDN because Kidd is weakly expressed by fetus

27

Duffy antigens

  • Fya and Fyb
  • present on DARC (Duffy associated receptor for chemokines), which is a receptor for plasmodium vivax
  • Fy(a+b-) is more common than Fy(a-b+)
  • Fy(a-b-) is rare in whites, but common in blacks (68%)
    • this phenotype confers resistance to plasmodium vivax
    • most Fy(a-b-) blacks do not form anti Fy antibodies, but Fy(a-b-) whites do

28

Duffy antibodies

- IgM or IgG

- dosage

- enzymes

- clinical conseqences

  • Duffy antibodies are warm reacting IgG antibodies acquired through exposure 
  • Duffy antibodies show dosage effect
  • Duffy antigens are destroyed by enzymes
  • Duffy antibodies are capable of causing hemolytic transfusion reactions (HTR) and severe hemolytic disease of the newborn

29

MNS antigens

  • MN and SsU genes display genetic linkage
  • most frequent haplotypes are Ns and Ms
  • M and N antigens are found on glycophorin A
  • 25% of population is M+N-
  • 25% of population is M-N+ 
  • 50% of population is M+N+
  • S, s, and U antigens reside on glycophorin B
    • s and U are high frequency antigens, present in over 98% of the population
    • S is present in 50% of whites and 30% of blacks
  • It is very difficult to find compatible blood for rare S-s-U recipients, who are usually black

30

MNS antibodies

  • anti M antibodies are naturally occurring, cold reacting, IgM antibodies that are clinically insignificant 
  • anti N antibodies are rare because an epitope on glycophorin B has N like antigenicity
  • anti Nf antibodies may be formed in dialysis patients who were exposed to formaldehyde used in cleaning dialysis machines and induced formation of Nf antigen on RBCs
  • Anti S, anti s, and anti U antibodies are acquired following exposure and are warm reacting, clincally significant, IgG antibodies
  • MNS antibodies display dosage
  • M and N antigenicity is destroyed by enzymes