What Are the Main Functions and Clinical Relevance of the MNS System?
As we know, blood is one of the most important parts of the human body. It is the medium through which different body systems operate smoothly as it provides the required amount of nutrients and oxygen. It is also a medium to transport the waste materials from the body and maintain body mechanisms. However, plasma is the major constituent of blood. Apart from that, several other things like RBC, WBC, and platelets are the sole constituents of the blood.
But depending upon the tiny substances present on the red blood cells MNS blood group system is derived. Tiny substances like M, N, S are known as antigens. The advanced genetic and anthropological studies of the human population revealed the presence of more than 40 antigens in the MN blood group. Initially, in the year 1927, the scientists located only two antigens, such as M and N and known as the MN Blood group. Later after 20 yrs another two antigens, S and s added to the list in the years 1947 and 51.
MNSs Blood Group Nomenclature:
Normally a protein consists of sugar attached to the MNSs called glycophorin. The blood group of the person is determined from the protein that attaches to the cell. The MNSs blood group is mainly denoted by two genes such as GYPA AND GYPB, containing glycoprotein A and Glycoprotein B. Another protein is also adjacent to glycoprotein B, which is CYPBthe allele for the MNS Blood group. The antigens in response produce antibodies; the antibodies of m and n don't show any incompatibility reaction. However, the antibodies of s and s show transfusion reaction and can cause erythroblastosis fetalis.
Usually, five common phenotypes are observed. Three most common phenotypes include M+n+s+s (24%) , M+N+ s+ s (22%) and M+ n+ s+s (15%) . Two other phenotypes were also observed, having a frequency of 33% and 19%.
Apart from this, some other phenotypes were also observed because of mutation with GYPA and GYPB. Example- GYPA allele produces Mta antigen by single nucleotide polymorphism, and that results in a change in amino acid threonine to isoleucine.
Sometimes we also observe rare blood groups such as En – ve because of the lack of glycophorin in the RBC membrane. This is the primary reason for the mutation. Deletion or erection of additional gene results In the formation of the mutants. Such rare blood groups like S-s-U are formed. Individuals having this unique blood group lack both glycophorin A and B. After deep microscopic observation, it is noticed that MNSs antigens are mainly found in RBC. Glycophorin A mainly forms around 1 million copies, whereas glycophorin B forms around 0.2 million copies. The antigenic character of the MN blood group was also noticed in the kidney.
The Function of MNS Antigen:
The two major proteins in the RBC, Glycophorin A, and B, act as a carrier for the receptor of cytokines, bacteria, and viruses. But the organism that lacks the glycophorin sufferer from the disease as their function is not significant. The advancement in the field of medical science allows scientists to analyze deeply. Recently it has been noticed that scientists are taking their interest in glycophorin because it forms MN antigen. This glycophorin may be the receptor of plasmodium falciparum, the causal organism of malaria in humans. So technically, the persons having rare blood groups are resistant to plasmodium.
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Molecular Data of MN Blood Group
GYPA and GYPB are the two primary proteins that are responsible for the encoding of the glycophorins in the MN blood group. Both the chromosomes show recombination reactions and are tightly linked. One can find both GYPA and GYPB in the long arm of chromosome 4.
Another gene present adjacent to the GYPB is GYPE. It is the gene that forms new alleles. Both the genes GYPA and GYPB contribute about 97% of the total homologous sequence. It also undergoes a duplication reaction.
The gene GYPA contains seven exons and having two forms of the allele, such as MNS 1 and MNS 2. These two alleles mainly produce two antigens, such as M and N. The two alleles are similar but from different amino acids such as serine at residue-1 and glycine at residue -5. GYPB has mainly five exons and having two alleles MNS3 and MNS4. It produces antigen S and s. Proteins like Methionine form at residue-29 and threonine at MNS4.
Glycophorin A and B are transmembrane proteins. At the negative charge surface of the RBC membrane, this Glycophorin A attaches and produces sialic acid. It has mainly three domains such as extracellular domain, intracellular domain, and spinning domain. The structure of Glycophorin B is similar to that of Glycophorin A, but the intracellular domains are shorter.
FAQs on MNS Blood Group System Explained
1. What is the MNS blood group system?
The MNS blood group system is one of the complex human blood group systems, identified after the ABO and Rh systems. The name is derived from its primary antigens: M, N, S, and s. These antigens are structures located on two important glycoproteins, Glycophorin A and Glycophorin B, found on the surface of red blood cells.
2. How is the MNS blood group inherited?
The inheritance of the MNS system is determined by two closely linked genes on chromosome 4, which control co-dominant alleles.
- The first gene determines the M and N antigens on Glycophorin A. A person can have the phenotype M, N, or MN.
- The second gene determines the S and s antigens on Glycophorin B. A person can have the phenotype S, s, or Ss.
3. How does the MNS blood group system differ from the ABO system?
The main differences between the MNS and ABO systems are based on their antigen structure, antibodies, and clinical relevance.
- Antigen Nature: ABO antigens are carbohydrates attached to the red cell surface, whereas MNS antigens are part of glycoproteins (proteins with attached sugars).
- Antibodies: In the ABO system, antibodies (anti-A, anti-B) are naturally occurring. In the MNS system, antibodies are typically immune-mediated, meaning they develop only after exposure to foreign antigens through transfusion or pregnancy.
- Clinical Impact: ABO incompatibility causes severe, immediate transfusion reactions. While some MNS antibodies are significant, anti-M and anti-N are often weaker and less likely to cause major issues.
4. What is the clinical significance of the MNS blood group system?
The clinical significance of the MNS system primarily relates to blood transfusions and pregnancy. While not as critical as ABO or Rh in routine testing, certain MNS antibodies can cause significant problems. Antibodies like anti-S, anti-s, and anti-U are of the IgG type and can cause delayed hemolytic transfusion reactions and Hemolytic Disease of the Fetus and Newborn (HDFN). Therefore, screening for these antibodies is important for patients needing multiple transfusions.
5. Can the MNS system cause Hemolytic Disease of the Fetus and Newborn (HDFN)?
Yes, some antibodies in the MNS system can cause HDFN, a condition where maternal antibodies attack fetal red blood cells. While anti-M and anti-N are typically IgM and do not cross the placenta, clinically significant IgG versions of anti-M can cause mild HDFN. More importantly, IgG antibodies like anti-S and anti-s are known causes of moderate to severe HDFN.
6. Why is the MNS system not as frequently matched in blood transfusions as the ABO and Rh systems?
The MNS system is considered less critical for routine matching because its most common antibodies, anti-M and anti-N, are usually 'cold-reactive'. This means they are most active at temperatures lower than the human body's core temperature and are often of the IgM class, making them less likely to destroy transfused red cells. In contrast, ABO antibodies are highly potent at body temperature, and the Rh(D) antigen is a primary cause of severe HDFN, making them the top priority for matching.
7. What is the biochemical difference between the M and N antigens?
The difference between the M and N antigens lies in the amino acid sequence of the Glycophorin A (GPA) protein on red blood cells. It is not a major structural change but a subtle variation.
- The M antigen has the amino acids Serine at position 1 and Glycine at position 5.
- The N antigen has Leucine at position 1 and Glutamic acid at position 5.
