Motivation

This year the work of iGEM Team Tübingen on the T-ECO project was all about the conversion of blood types to provide an improved blood supply for patients in emergency and to thereby save lives.

The human blood can be classified into several groups based on the presence of certain antigenic structures on the surface of red blood cells. In total 33 blood-group systems have been identified [1], while the ABO system is the most important system in human-blood transfusion.

Figure 1: ABO blood type system. Oligosaccharide structures on red blood cells act as antigens. Based on the oligosaccharide of group O, group A contains an additional N acetyl-galactosamine and group B has an additional Galactose attached to it. Red blood cells from group AB carry both types of oligosaccharides [2].

While the plasma of group A contains antibodies against antigens of group B and the other way round, the plasma of group O contains both antibodies. In the case of group AB no antibodies against an A or B antigen are present. This properties directly explain the compatibility of blood groups in the case of a blood transfusion, as shown in Table 1.

By referring to the blood group compatibility it is obvious that blood group O is the optimal donor blood for blood transfusion. And patients from the other groups can be supplied with blood preservations of at least one additional type. On the other hand patients from group O are dependent on a supply of blood type O only. The blood type distribution of the population in the USA for example is as follows: 44 % of the population is type O, 42 % is type A, 10 % is type AB and 4 % is type AB.

The current blood donation and reception system in transfusion medicine bases on this comparison of blood groups. It requires to test the blood of the involved people at least once for the donor, once for the recipient and additionally right before the supply in form of a bedside compatibility test. These tests are time consuming, which can be critical in some situations for the life of the patient.

Although the blood groups of donations are roughly equally distributed as the overall distribution in a country, rare blood preservations may get scarce quickly dependent on the case of emergency. When a patient with a rare blood group needs a big amount of blood preservations the stock can diminish rapidly. In the worst case, this then may lead to the inability to supply a patient with the correct blood type, which may have direct influence to the chance of survival. On the other hand preservations of blood groups with higher frequency are excessively available and may be useless during their storage life. Due to this phenomena huge amounts of unused blood preservations are discarded continuously in blood institutes, due to the impossibility to use them.

However, blood groups can be converted. As shown in figure 1 the nature of an ABO blood group is the composition of oligosaccharides that are physically exposed on the exterior of red blood cells. Specific glycosidases, derived from bacteria can remove monosaccharides from these oligosaccharides and therefore convert the blood groups A, B and AB to O. In our case we wanted to use the following enzymes: N-acetylgalactosaminidase (NAGA) from Elizabethkingia meningoseptica to convert type A to O, α-Galactosidase (αGAL) from Bacteriodes fragilis to convert type B to O [3]. To convert type AB to O one could apply both enzymes or another enzyme we used: Endo-β- galactosidase (EABase) from Clostridium perfringens. This process could be realized technically by immobilizing the enzymes onto a column. To convert a blood preservation, it is only necessary to apply the preservation onto the column. The process of conversion can therefore get highly automatized.

So a new blood donation and reception system making use of converted blood cells could improve several aspects of the transfusion medicine. First of all the amount of blood tests would decrease. All donations would be immediately converted and the only blood test would be a blood quality control after conversion is done. Patients with rare blood groups now can be supplied sufficiently with blood preservations and there will not be a deficit of a certain blood group again. Due to the consequent conversion of blood cells, all blood preservations will be able to be used. This would result in a more efficient use of donated blood and in less disposal of preservations. Moreover, an automated process would result in faster handling and more efficient preservation supply of patients.

Last but not least, the possibility to supply preservations to every patient in nearly any amount and higher performance will save lives.

References

[1] Joshua E. Brown (22 February 2012). "Blood Mystery Solved". University Of Vermont. Retrieved 11 June 2012.

[2] (2014) http://en.wikipedia.org/wiki/Blood_type

[3] Liu, Q.P., Sulzenbacher, G., Yuan, H., Bennett, E.P., Pietz, G., Saunders, K., Spence, J., Nudelman, E., Levery, S.B., White, T., Neveu, J.M., Lane, W.S., Bourne, Y., Olsson, M.L., Henrissat, B. & Clausen, H. (2007). Bacterial glycosidases for the production of universal red blood cells. Nature biotechnology 25, 454-464.