Mix and Match - Blood Group Systems

I would like to share a blog with you on the topic of structure and function of blood group antigens. Let’s play a game of using the following key to match five clues given to each answer. If you get the right answer after one or two clues, you are pretty good!  You can look up the AABB Technical Manual (17^th or 18^th ed) for more information.  Have fun! :-)
 
Mix and Match - Blood Group Systems
 

1. Kell
2. Lutheran
3. Gerbich
4. Cromer
5. Dombrock
6. MNS
7. Knops
8. Kidd
9. Duffy
10. Diego

1. Clues

1. This blood group system BGS has structural and sequence homology with a family of zinc-dependent endopeptidases that process a variety of peptide hormones. Although the function of this glycoprotein is not known, it is enzymatically active and is able to cleave the biologically inactive peptide big-endothelin-3 to create the biologically active vasoconstrictor endothelin-3. However, null phenotype has not been linked to any clinical abnormality.
2. This BGS resides on a single pass Type II membrane glycoprotein with a cytoplasmic N- terminal (compare with the more common type 1single pass polypeptide with the amino end on the outside of the mammalian membrane).
3. Conformation of this BGS is dependent on disulfide bonds which are susceptible to reducing agents such as 0.2M DTT and 6%AET.
4. The most common antibody of this BGS is significant even at lower concentrations to cause HDFN as its antigen is well developed in the red cell precursors before hemoglobin synthesis peaks.
5. Although rare in Asia, this IgG antibody is a common antibody that can cause hemolytic transfusion reactions and HDFN .

2. Clues 

1. Residing in a multipass membrane glycoprotein of about one million copies per red cell, this BGS constitutes up to 20% of the total membrane protein.
2. The protein is responsible for the rapid exchange of bicarbonate and chloride ions which is important in the transport of carbon dioxide across the red cell membrane, it also anchors the red cell membrane to the cytoskeleton.
3.  Commonly known as Band 3 or Anion Exchanger, it requires glycophorin A for correct folding of protein to be transported to the red cell membrane.                       
4. An antigen, rare among whites, in this BGS has been widely used for anthropological studies on migration of humans from Mongolia to the west coast of Americas. It is present at a much higher frequencies in other ethnic groups: Chinese (2-5%), Japanese (3-12%) and up to 40% in some American tribes.
5. Antibodies to the low incidence antigens can cause HDFN; with a positive DAT and a negative antibody screen on maternal sample, a definitive test is to obtain an eluate from cord blood and run against the paternal red cells. If the maternal sample is ABO compatible with father’s red cells, an IAT can also be used.

3. Clues

1. Antigens of this BGS are located on a type 1 single pass membrane glycoprotein with five extracellular immunoglobulin superfamily IgSF domains. As an adhesion molecule, it interacts with laminin, a glycoprotein found in the extracellular matrix.
2. Up-regulation of this BGS may be significant in the vascular occlusion crisis in sickle cell anemia as this BGS is thought to play a role in the migration of late stage maturing red cells from the bone marrow into peripheral circulation.
3. The null phenotype is due to the presence of an inhibitor gene that also depresses expressions of P₁, In^b and AnWj.
4. Antigens of this BGS are thermal labile and are dependant on disulfide bonding for integrity. Therefore, they are susceptible to destruction by 0.02M DTT and 6% AET. However, papain and ficin have no effect.
5. Antibodies are uncommon as the antigens are poor immunogens, if present, they are not being detected as  antibody screening cells are not required to carry the antigens.

4. Clues

1. This BGS is located on a multi-pass membrane glycoprotein which is also a receptor of many chemokines including interleukin-8 , monocyte chemotactic protein-1 and melanoma growth stimulating activity.
2. The null phenotype is extremely rare among Caucasians but abundant among Blacks, it is due to a mutation of the promotor region of the gene responsible for this glycoprotein. It is a selective advantage for survival in endemic areas of certain protozoan infection especially in Africa. On the other hand, the lack of this chemokine receptor may be linked to higher incidence of prostate cancer among African men.
3. Syntenic to RHD, RHCE, SC,DAF and CR1on chromosome 1, DARC encodes a glycoprotein which this BGS resides.
4. The most common antibody detect an antigen with a frequency similar to Do^a which, in contrast the common antigens in this BGS, is resistant to papain and ficin.
5. The antibodies of this BGS are mostly IgG1 and can cause hemolytic transfusion reactions and HDFN.

5. Clues

1. This BGS is located on two single pass sialoglycoproteins with one is shorter than the other by 21 amino acid residues at the cytoplasmic c-terminal.
2. GYPC is the gene encoding both proteins with the longer one attached to cytoskeletal proteins such as adducin, 4.1R and p55. Absence of GYPC is associated with hereditary elliptocytosis presented as the Leach Phenotype.
3. There is some evidence showing Leach phenotype are less likely to be invaded by certain strains of Plasmodium falciparum in vitro. In addition, there is a higher incidence of individuals lacking some higher incidence antigens in this BGS among Melanesians in Northern New Guinea suggesting a selective advantage.
4. Papain is useful to identify antibody to one high incidence antigens in this BGS as others are sensitive.
5. Although the majority of the antibodies are clinically insignificance, mild cases of hemolytic transfusion reactions and HDFN have been reported.

6. Clues    

1. Both amino and carboxylic ends of this multipass red cell membrane glycoprotein with 10 spanning domains and one glycosylation site, are embedded in the cytoplasm. 
2. Similar to other mutlipass membrane transport proteins, this BGS is responsible for transporting urea.
3. The lack of urea transporters in the null phenotype would make these rare red cells resistant to lysis in a 2M urea solution, a reagent used to locate donors.
4. Rare donors of the null phenotype have a much higher incidence among Polynesians, Filipinos and Chinese.        
5. Antibodies of this BGS are notorious to cause delayed hemolytic transfusion reactions as the antibody level drops more rapidly after stimulation, they can also cause HDFN. 

7. Clues      

1. Antigens of this BGS are located on the decay accelerating factor DAF (CD55) which is a negative70kd complement regulatory glycoprotein. DAF is not restricted to red cell membrane but is also found on white cells, platelets, plasma and urine.
2. The null phenotype is also known as the Inab phenotype. When alloimmunized, these rare Inab individuals may produce anti-IFC, a high incidence antigen.
3. This BGS is much weaker or even not detectable by IAT in patients with severe cases of paroxysmal nocturnal hemoglobinuria type III PNH III.
4.  The antigens are resistant to papain and ficin but destroyed by chymotrypsin. Although 6% AET can be used to treat normal red cells to become “PNH-like”, it only weakens the expression but not immunogenicity.
5. Although clinically insignificant, the IgG antibody is readily neutralized by platelet concentrate (pooled from two to three donors or commercially available kit)) to prevent interference from detecting clinically significant antibody.

8. Clues

1. Antigens of this BGS are found on a complement activation controlling single pass glycoprotein  called complement receptor 1 CR1or CD35
2. Many high incidence antigens of this BGS were defined by those so-called high-titred low avidity HTLA  antibodies .
3. The Helgeson phenotype represents the null phenotype. Although CR1 is not completely absent, Helgeson red cells are useful in conventional serology because it is non reactive using IAT.
4. Antigens are destroyed by chymotrypsin and trypsin but not by ficin and papain. Therefore,trypsin is an important reagent to differentiate antibodies to this BGS from others that may exhibit the HTLA titration characteristics.
5. Antibodies are considered as “nuisance” antibodies as they direct against high incidence antigens and have no clinical significance while masking the “wanted” antibodies.

9. Clues

1. Immunized individuals with the null phenotype of this BGS may develop anti-Gy^a.
2. Similar to Cromer, Cartwright and JMH, this blood group system is attached to the red cell membrane by a glycolipid called glycosyl phosphatylinositol or the GPI-anchor.
3. Antigens of this BGS are sensitive to proteolytic enzymes chymotrypsin, trypsin, pronase as well as by reducing agents DTT and AET.
4. Not listed in commercial panels, the most common antibody of this BGS detects an antigen with a similar frequency as Fy^a; unlike Fy^a, the antigen is resistant to papain and ficin.
5. Antibodies have been reported to cause hemolytic transfusion reactions but not HDFN, because of the scarcity of antisera, compatible donor units can be identified by DNA technology.

 10. Clues

1. This highly polymorphic BGS is located on two single pass  glycoproteins that has over a million copies on each red cell. The longer glycoprotein (131 amino acid residues) is unique to red cells therefore it is used as an erythroid marker. The extracellular hydrophilic domain (res1-72) is glycosylated and the hydrophobic domain ( res 73-95) is embedded in the membrane while the cytoplasmic domain (res 96-131) is hydrophilic and has the carboxylic terminus. The shorter single pass glycoprotein (71 amino acid residues) with a much shorter cytoplasmic domain of eight amino acids.
2. The N-/O-linked oligosaccharides attached to these proteins are responsible for the net negative charge of red cells as they are rich in sialic acids. Exposure of the crypt antigens by bacterial or viral sialidase may result in polyagglutination. ABH and CAD antigens can also be found.
3. Substitution of one or two amino acids and hybridization of the two closely linked genes are responsible for  the polymorphism of this BGS. An example of a hybrid gene product is the GPMur antigen, the K counterpart in south east Asia.
4. Anti-En^a and anti-U are antibodies developed by individuals who lack the longer and shorter  glycoprotein known as glycophorin A and glycophorin B respectively. The null phenotype of this BGS is the result of  homozygosity of the rare M^k gene.
5. Antibodies of this BGS are significant if reactive at 37C. Routine transfusion service using tubeless technologies (solid phase and column agglutination) have detected these antibodies less frequently.

 Answers
      1. a   2. j   3. b   4. i   5. c   6. h   7. d   8. g   9. e   10. f
 
     Have a wonderful time with your family and friends in the upcoming festive season.