Transfusion medicine The M and N antigens differ at two amino acid residues: the M allele has serine at position 1 (C at nucleotide 2) and glycine at position 5 (G at nucleotide 14) while the N allele has leucine at position 1 (T at nucleotide 2) and glutamate at position 5 (A at nucleotide 14). Both glycophorin A and B bind the
Vicia graminea anti-N lectin. There are about 40 known variants in the MNS blood group system. These have arisen largely as a result of mutations within the 4 kb region coding for the extracellular domain. These include the antigens Mg, Dantu, Henshaw (He), Miltenberger, Nya, Osa, Orriss (Or), Raddon (FR) and Stones (Sta).
Chimpanzees also have an MN blood antigen system. In chimpanzees M reacts strong but N only weakly.
Null mutants In individuals who lack both glycophorin A and B the phenotype has been designated Mk.
Dantu antigen The Dantu antigen was described in 1984. The Dantu antigen has an apparent molecular weight of 29 kilodaltons (kDa) and 99 amino acids. The first 39 amino acids of the Dantu antigen are derived from glycophorin B and residues 40-99 are derived from glycophorin A. Dantu is associated with very weak s antigen, a protease-resistant N antigen and either very weak or no U antigen. There are at least three variants: MD, NE and Ph. The Dantu phenotype occurs with a frequency of Dantu phenotype is ~0.005 in American Blacks and < 0.001 in Germans.
Henshaw antigen The Henshaw (He) antigen is due to a mutation of the N terminal region. There are three differences in the first three amino acid residues: the usual form has
Tryptophan1-Serine-Threonine-Serine-
Glycine5 while Henshaw has
Leucine1-Serine-Threonine-Threonine-
Glutamate5. This antigen is rare in Caucasians but occurs at a frequency of 2.1% in US and UK of African origin. It occurs at the rate of 7.0% in blacks in
Natal and 2.7% in West Africans. At least 3 variants of this antigen have been identified.
Miltenberger subsystem The Miltenberger (Mi) subsystem originally consisting of five phenotypes (Mia, Vw, Mur, Hil and Hut) now has 11 recognised phenotypes numbered I to XI (The antigen 'Mur' is named after to the patient the original serum was isolated from - a Mrs Murrel.) The name originally given to this complex refers to the reaction erythrocytes gave to the standard Miltenberger antisera used to test them. The subclasses were based on additional reactions with other standard antisera. Mi-I (Mia), Mi-II(Vw), Mi-VII and Mi-VIII are carried on glycophorin A. Mi-I is due to a mutation at amino acid 28 (threonine to methionine: C→T at nucleotide 83) resulting in a loss of the glycosylation at the asparagine26 residue. Similar to the case of Mi-I this mutation results in a loss of the glycosylation at the
asparagine26 residue. This alteration in glycoslation is detectable by the presence of a new 32kDa glycoprotein stainable with PAS. Mi-VII is due to a double mutation in glycophorin A converting an
arginine residue into a threonine residue and a
tyrosine residue into a serine at the positions 49 and 52 respectively. The threonine-49 residue is glycosylated. This appears to be the origin of one of the Mi-VII specific antigens (Anek) which is known to lie between residues 40-61 of glycophorin A and comprises sialic acid residue(s) attached to O-glycosidically linked oligosaccharide(s). This also explains the loss of a high frequency antigen ((EnaKT)) found in normal glycophorin A which is located within the residues 46–56. Mi-VIII is due to a mutation at amino acid residue 49 (
arginine->threonine). M-VIII shares the Anek determinant with MiVII. Mi-III, Mi-VI and Mi-X are due to rearrangements of glycophorin A and B in the order GlyA (alpha)-GlyB (delta)-GlyA (alpha). Mil-IX in contrast is a reverse alpha-delta-alpha hybrid gene. Mi-V, MiV(J.L.) and Sta are due to unequal but homologous crossing-over between alpha and delta glycophorin genes. The MiV and MiV(J.L.) genes are arranged in the same 5' alpha-delta 3' frame whereas Sta gene is in a reciprocal 5'delta-alpha 3' configuration. The incidence of Mi-I in
Thailand is 9.7%. Peptide constructs representative of Mia mutations MUT and MUR have been attached onto red blood cells (known as
kodecytes) and are able to detect antibodies against these Miltenberger antigens Although uncommon in Caucasians (0.0098%) and
Japanese (0.006%), the frequency of Mi-III is exceptionally high in several
Taiwanese aboriginal tribes (up to 90%). In contrast its frequency is 2-3% in Han Taiwanese (Minnan). The Mi-III phenotype occurs in 6.28% of Hong Kong Chinese. Mi-IX (MNS32) occurs with a frequency of 0.43% in
Denmark.
Stone's antigen Stones (Sta) has been shown to be the product of a hybrid gene of which the 5'-half is derived from the glycophorin B whereas the 3'-half is derived from the glycophorin A. Several isoforms are known. This antigen is now considered to be part of the Miltenberger complex.
Sat antigen A related antigen is Sat. This gene has six exons of which exon I to exon IV are identical to the N allele of glycophorin A whereas its 3' portion, including exon V and exon VI, are derived from the glycophorin B gene. The mature protein SAT protein contains 104 amino acid residues.
Orriss antigen Orriss (Or) appears to be a mutant of glycophorin A but its precise nature has not yet been determined.
Mg antigen The Mg antigen is carried on glycophorin A and lacks three O-glycolated side chains.
Os antigen Osa (MNS38) is due to a mutation at nucleotide 273 (C->T) lying within exon 3 resulting in the replacement of a
proline residue with a
serine.
Ny antigen Nya (MNS18) is due to a mutation at nucleotide 194 (T->A) which results in the substitution of an
aspartate residue with a glutamate. Raddon has been associated with severe transfusion reactions. ==Relevance for infection==