Rhesus and Other blood groups- amanda Flashcards
When was Rhesus blood group first mentioned?
1939
Levine and Stetson described a mother who gave birth to still born child and despite being ABO compatible with her husbands suffered a transfusion reaction when transfused his blood
Who discovered another blood type Rh factor- antigens that is either present or absent indicated with a + or -
Landsteiner and Wiener in 1940
How was the antigen discovered?
Discovered in blood of Rhesus monkey whilst doing an experiment with red cells from the monkey which were transfused to rabbits and other rodents
What did they also discover in blood of Rhesus monkey
Not only did the antibody in the rodents serum agglutinate the Rhesus monkey red cells, it also agglutinated the red cells of 85% of the human population.
Rh antigen
Another surface protein that is found on the surface of red blood cells .
An individual either has the Rh factor on RBC + or doesn’t - , genetically determined
- individuals who are Rh- will produce antibodies that attack Rh+ cells
- particularly dangerous if a mother is Rh- and her foetus is Rh+
If a person has both A and Rh antigens what is there blood group?
A+
True or False: People that are Rh negative do not produce antibodies against Rh antigen unless they are exposed to the antigen
True
Who identified an antibody reacting against blood donors with the same frequency as anti-Rh in transfusion recipients
Weiner and Peters
Blood Group RH system
- comprises some 56 antigens (61 previously described but 5 now obsolete)
- first antigen=RhD.
Phenotype is RhD positive/negative
Genotype- RHD
When is somebody said to have the Rhesus factor on their red cells (I.e. RhD positive)
When an individuals red cells are agglutinated by antiserum containing anti-D
Somebody lacks the Rhesus factor (I.e., RhD negative)
When an individuals cells are not agglutinated by the antiserum containing anti-D
What is multipass antigen thought to be involved in?
Maintaining structural integrity as well as transporting ammonium or carbon dioxide for exchange in the liver or kidney where RH associated antigens reside
What do Rh Null cells form
Stomatocytes with reduced lifespan due to association with intergrin associated protein CD47
What proteins are present in the kidney, liver, brain, and skin where ammonia production and elimination occur?
Non erythrocytes Rh glycoproteins RHBG and RhCG
What are the functions of the RH system proteins?
- Integrity of the red blood cell structure
- Ammonium transport
What is the most immunogenic and the first antigen of the Rhesus system?
RhD
What are the Rhesus antigens most frequently referred to?
Rh- D. -C, -E, -c, -e
True or false- there is no Rh-d antigen
True.
D negative denotes absence of RhD antigen
Percentages of RhD positive in populations
82-85% Caucasians
95% black Africans
100% Far East
When is the RhD antigen developed?
Early gestational period
RHD gene
Produces D antigens
RHCE gene
Produces Cc and Ee antigens
Are Rh antibodies mostly immune antibodies
Yes
What is responsible for most clinical problems
Anti-D
Used to identify RhD positive and negative individuals
Are rhesus antibodies usually naturally occurring?
No
Can anti-D antibodies develop in a RhD negative person who is exposed to blood from an RhD positive individual ?
Yes
What are the two mechanisms of sensitisation ?
- incompatible transfusions
- pregnancy
Why is the RH system so important?
- severe haemolytic transfusion reactions
- haemolytic disease of the newborn : 50% of all pregnant women who make antibodies make antibody specificities to one of the antigens of the Rh system
- Implicated as autoantibody specificity in cases of Warm Autoimmune haemolytic anaemia
When was the Kell Blood group system discovered?
1946
What is the estimation of individuals who are Kell negative when exposed to Kell positive red cell will make anti-K
Approximately 1:20
How many Kell antigens have been discovered
37
What is the K antigen of prime importance in transfusion medicine and HDN?
Original K antigen
Where is the Kel gene located?
Chromosome 7, with 19 coding sequences (exons)
What is the Kell glycoprotein also known as?
CD238
GENE FOR Xk coded on X chromosome
KEL2, KEL4, KEL7
High incidence in all populations
KEL3
2% of Caucasians but not present in Africans or Japanese
KEL1
9% Northern Europeans, 1.5% African descent, Rare In east asia
KEL10
Only found in Finns and Japanese
KEL6
Confined to African populations, frequency of 16%
McLeod Syndrome
- Reduction or absence of Kell glycoprotein and Kx
- very rare X linked condition so almost exclusively found in boys
- associated with acanothocytes, reduced red cell survival, and reticulocytosis
- muscular and neurological defects may also be observed
- McLeod syndrome occasionally associated with X linked disorder of chronic granulomatous disease (CGD)
CGD
Associated with defective phagocytic cell kill mechanism whereby microorganisms engulfed but not killed by phagocytes, patients susceptible to infection
What does CGD arise from
Deletion of X chromosome material which spans both loci.
Caused by mutations in any one of four genes that encode the subunits of phagocyte NADPH oxidase, the enzyme that generates microbicidal (and pro-inflammatory) oxygen radicals.
NADPH oxidase
Enzyme that generates microcidal oxygen radicals
Kell Antibody characteristics
- IgG immune antibodies detectable by LISS AGT test
- Implicated in transfusion reactions
- HDN- well developed at an early stage of foetal development
-associated with reduced reticulocytosis and erythroblastosis - not associated with hyperbilirubinaemia
- specificities with AIHA
Kell antibodies
- reactive at 37 degrees Celsius in AHG test, protease treatment of red cells does not effect Kell antigens
- detectable in papain tests
What else is Kell antibodies implicated in?
Haemolytic disease of newborn
Well developed in foetal cells at an early stage of foetal development
Causes fatalities
Kell specificities also cited in cases of patients with…
Both drug-induced and idiopathic AIHA
Patients can transiently demonstrate weakening of the Kell system antigens and DAT may be only very weakly positive or negative.
As the AIHA resolves to the levels of Kell system antigens return to normal
Duffy (FY) Blood group system
- discovered in 1950
- named after a patient with haemophilia who had received multiple blood transfusions and was first known producer of anti-Fay
- year later anti-Fyb was discovered in a woman who had several children
-only FY3 appears clinically significant
-erythrocytes and non-erythroid distribution (epithelial cells of kidney collecting ducts, lung tissue, purkinje cells of brain) - frequency varies in different populations
Is Duffy present on lymphocytes, monocytes, granulocytes and platelets?
No
Where are Duffy protein antigens , CD234, encoded for?
Chromosome 1
More info on Duffy blood group system
5 antigens total, 2 major co-dominant alleles FYA and FyYB. Which result from a SNP
Duffy glycoprotein
Receptor that binds cytokines during inflammation
Duffy antigen receptor of chemokine
DARC
Chemokine receptor on RBCs
DARC
- receptor for 60% all inflammatory chemokine for both C-X-C and C-C classes
- chemokine binding protein with no signalling function
Function of DARC
Sink to bind excess chemokine prevents activation of neutrophils- benign ethnic neutropenia
- reservoir for chemokine to maintain plasma chemokine concentration
True FY(a-b-) phenotype
Have no obvious haematological or immunological abnormalities
One mechanism for releasing chemokine from red cell surface
Clotting
Fy(a-b-) phenotype and malaria
- Fy(a-b-) cells lack any Duffy glycoprotein expression on the RBC surface
-Fy antigens are receptors for Plasmodium vivax merozoites (particularly associated with Fy6 expression) - Fy antigen serves as a receptor molecule for attachment of merozoites, absence of Fy antigens afffords selective advantage
- Does not apply to other Plasmodium strains e.g., Plasmodium falciparum
Duffy antibody characteristics
- Mainly IgG, as IgM is rare
- stimulate by pregnancy/transfusion severity for both varies although usually mild HDFN
- Anti-FYA 20x more common than anti-Fy in Caucasian populations
-reactivity at 37 degrees, detected in AHG test
-alloimmunisation to Duffy antigens not high indicating poor immunogenicity
Duffy antibodies and HDN
Not a frequent cause, and where reported result in only mild cases requiring exchange transfusion
Disease associations
- malaria
- benign ethnic neutropenia
-HIV disease progression - sickle cell disease- disease severity and organ damage
-severity of immune reactions in autoimmune conditions - suppressive effect on angiogenesis and metastasis of cancer cells (interaction with CD82 which is a suppressor of metastasis)
