MNS blood group is the second blood group that has been discovered right after the ABO system and so it got the ISBT number 002. The first antigens that were discovered are M and N by Landsteiner and Levine at 1927. And that was by finding anti-M and anti-N in a rabbits blood that was immunized with human RBCs. At 1947, anti-S was detected and so Walsh and Montgomery discovered the S antigen. At 1951, Levine found anti-s. This system was named after the first three antigens that were discovered MNS. (Daniels G. 2008)
There are 46 antigens known now in this group those antigens are M, N, S, s, U, He, Mia, Mc, Vw, Mur, Mg, Vr, Me, Mta, Sta, Ria, Cla, Nya, Hut, Hil, Mv, Far, sD, Mit, Dantu, Hop, Nob, Ena, ENKT, ?N?, Or, DANE, TSEN, MINY, MUT, SAT, ERIK, Osa, ENEP, ENEH, HAG, ENAV, MARS, ENDA, ENEV, and MNTD. (Reid M.E. 2009)
The most important antigens are M, N, S, s and U. In this research, we will cover the first four antigens only. As we are going to study the frequencies of MNS antigens in our population, we should compare it to other populations. After looking through other studies, those were the Frequencies of the MNS antigens in Caucasians, blacks, Chinese, and Indian.
Table 2.1 Frequencies of the MNS antigens in other populations
(Reid E, et al. 2012)
(Reid E, et al. 2012)
(Y. Yu, et al. 2016)
(Thakral, B. et al. 2010)
As we can see in the table the frequencies in different populations showed a significant differences in some antigens. First, the Chinese population, this study was carried out on a 1412 randomly selected blood donors using serological technology in DG Gel Neutral card. The results after that were compared to other populations and even though it showed a close ratio for antigen M to all the other three populations, N antigen were slightly higher than the Indian, as for S frequency its significantly lower than all the other populations in the table. Also the frequency of s were significantly higher. (Y. Yu, et al. 2016)
Secondly, the Indian population. This study were carried out on 1240 blood donors with O blood group using gel technique. The results showed a lower N frequency to the other 3 populations and a higher S frequency than Chinese and blacks, while s frequency were lower than Chinese and blacks (Thakral, B. et al. 2010). In the end of this study we are going to compare our results to those four populations and see the similarities and differences between us.
The MNS antigens are proteins that are carried on a glycoproteins carrier molecules, which is a transmembrane, single-pass membrane glycoprotein that known as Glycophorins. There are two type of glacophorins, Glaycophorin A (GPA), which carry the M and N antigens, and Glaycophorin B (GPB) which carry the S and s antigens. As for their structures, M differs from N in the two amino acids at position 1 and position 5. M has serine at position 1 and glycine at 5, while N have leucine in position 1 and glutamate in 5. On the other hand, S differs from s in a single amino acid at position 29. As S have Met at that position while s have Thr. The MNS antigens are expressed mainly on the RBCs, every RBC carry about one million copies of GPA and 0.2 copies of GPB, those antigens also present on the kidneys. As for infants, they’re are expressed on the cord RBCs and well developed on birth.
On a genetic background, a cluster of three genes located on the long arm of chromosome 4 codes the MNS system. Those genes are GYPA, GYPB and GYPE. GPYA consist of seven exons code for Glycophorin A (GPA), while GYPB which was first sequenced in 1987 consist of five exons encode for Glycophorin B (GPB) and one pseudoexons. GYPA have 97% homology with GPYA. GYPE consist of four exons and two pseudoexons . it does not encode for an antigen, but it participates in gene rearrangements, which result in variant alleles. (Daniels G. 2008)
Figure 2.1 Genomic organization of GYPA, GYPB, and GYPE
M and N antibodies are usually naturally occurring, cold antibodies. Anti-M contain both IgG and IgM immunoglobulin classes though the IgG usually cold reactive here. The ratio is about 78% IgG and 22% IgM (J. Crumlish, et al. 2012). Anti-M and anti-N both reacts in 4°C and RT (room temperature), rarely they can react in 37 °C. Even though those two antibodies generally consider as an insignificant antibodies but in rare cases when they react in the 37 they should be considered. In some rare cases anti-M can cause HDN and HTRs and even though it is rare, when it happens it is often severe. (Reid E, et al. 2012)
S and s antibodies are usually an immune antibodies which means they’re acquired after exposure, generally they consider clinically significant as they react at IAT. Anti-S may react at RT too; it is mostly IgG but can also be IgM. While anti-s usually in IAT though it might react sometimes in the RT and four after incubation. The immunoglobulin class is usually IgG. Both anti-S and anti-s can cause mild to severe HTRs , both of them can also cause a severe HDN but anti-S is more common. (Dean L. 2005)
The MNS antigens generally become inactivated by the effect of Proteolytic enzymes such as ficin and papain. These enzymes cause the cleavage and degradation of various proteins, resulting in decreasing the strength of MNS antigens. In more details M and N are Sensitive to Ficin, papain, Trypsin, and Pronase. In the other hand they are resistant to ?-Chymotrypsin, DTT 200mM, and acid, as for Sialidase they show variable reactions. S and s shows a variable reactions with Ficin, papain, and Sialidase. Sensitive to ?-Chymotrypsin, and Pronase. And resistant to Trypsin, DTT 200mM and Acid. (Reid E, et al. 2012)