Antigens: It is a complex system, consisting of over 40 glycoproteic antigens. The M, N, S, s antigens together with U (a high-frequency antigen) are the most relevant in Transfusion Medicine. The M and N antigens are localized on glycophorin A; S, s, and U are located on glycophorin B. The genes encoding these antigens exhibit marked link age disequilibrium. As an example, the Ns gene complex is more frequent than NS. The MNS system also includes numerous low-frequency antigens, resulting from mutations involving amino acid substitutions and from modifications in glycation.
The genes that code for the antigens of the MNS system are located on chromosome 4. The gene that codes for glycophorin A is called GYPA, the gene that codes for glycophorin B is called GYPB. The two genes, which probably derive from a single ancestral progenitor, have a homology greater than 95%. Glycophorin A is a transmembrane glycoprotein present in approximately 1,000,000 copies for each erythrocyte. The M and N antigens are located in an extracellular portion consisting of 72 amino acid residues linked to side glucose chains. M specificity is characterized by a serine in position 1 and a glycine in position 5; the specificity N is characterized by a leucine in position 1 and a glutamate in position 5. Glycophorin B is smaller and is present in about 200,000 copies for each erythrocyte. The specificity S is characterized by a methionine in position 29, this position is occupied by a threonine to give the specificity s. Usually the M and N antigens are destroyed by treatment with proteolytic enzymes such as ficin or papain.
Antibodies: Anti-M is frequently detected as a cold reactive agglutinin with red cells suspended in physiological solution. These antibodies are usually of the IgM class (although the finding of IgG is not uncommon) and are frequently observed in the serum of subjects who have never been exposed to nonself human erythrocytes. These are anti bodies that only rarely take on clinical significance, although they have been implicated in rare cases of PTH and HDFN. These were mostly IgG class antibodies able to react at 37 °C or with the antiglobulin test.
Anti-N is a relatively rare antibody, it is usually of the IgM class, and behaves like a cold agglutinin. They are not considered clinically significant antibodies. The “anti-S” and “anti-s” antibodies are usually immune antibodies of the IgG class, identifiable by the antiglobulin test. They are considered clinically significant, being implicated in PTH and HDFN. Anti-U is rare but should be considered if a reactive antibody against a high frequency antigen is identified in a subject of African origin previously exposed to nonself red blood cells.
