WEDNESDAY, 14 MAY 2014
Subsequent work elucidated the mechanisms behind these dramatic reactions. All red blood cells are O-positive by default and it is the presence of a specific enzyme, either an A or B enzyme, that dictates whether an A or B sugar will be added to the core carbohydrates that coat red blood cells.
Agglutination of red blood cells occurs when antibodies (immune proteins that recognise and help destroy harmful molecules) target foreign blood group carbohydrates. Antibodies against foreign blood groups naturally develop in humans. However, the immune system of an A-positive individual will not allow the production of antibodies that target A sugars. In other words it will not recognise its own cells as foreign or threatening. Similarly, in a B-positive individual no anti-B antibodies develop. If someone’s blood group is O, their immune system will make both anti-A and anti-B antibodies. If someone with an O-positive blood type is transfused with A- or B-positive blood, their antibodies will destroy these new red blood cells. In 1 out of 20 cases this leads to sudden death.
But why do the different blood groups exist? Is there a benefit in having different blood types?
Exactly why there is a mixture of different blood types in many species is indeed a mystery. One hypothesis is that pathogens may have played a role in the evolution of blood types. Many pathogens use carbohydrates from the cell surface as receptors to bind to the cell. Receptors can also be used as anchors to prevent from being swept away and they might help a pathogen enter the cell or release its toxins inside it. Depending on their blood type, people are more or less susceptible to certain pathogens. If you do not express a pathogen’s receptor but your neighbour does, you will be safe from infection but your neighbour might fall ill.
Cholera was the first infectious disease shown to affect people in different ways according to their blood group. The responsible bacterium, Vibrio cholerae, causes severe watery diarrhoea and can be fatal if appropriate treatment is not received. Outbreaks in the developing world usually have devastating consequences, as happened in a recent epidemic in Haiti, which resulted in over 8,000 deaths.
In the 1970s researchers noticed that individuals with blood group O were more likely to become infected with cholera than people with blood group A or B. Because V. cholerae is a bacterium that causes infection in the gut, the fact that blood groups mattered was a mystery.
Once the properties of histo-blood group antigens were understood in more detail, an association between cholera infection and blood groups could be explained by focusing on the carbohydrates present in the gut. The current theory is that A and B carbohydrates on the cell surface block the binding of the cholera toxin to its receptor molecule, ganglioside GM1, which is also located on the cell surface. People who do not have A or B carbohydrates on their cells cannot disrupt this interaction, and hence the cholera toxin enters the cell and causes disease.
For a long time, researchers had suspected that the carbohydrates that determine blood groups could enable pathogens to enter cells, not merely their toxins. In 2002, the first pathogen that uses receptors in this way was finally identified. Human norovirus, the cause of the winter vomiting bug that infects up to three million people in the UK every year, was shown to bind to blood group carbohydrates and enter the cell. The first norovirus strain studied turned out to bound strongly to A and O blood groups, but less efficiently to B. This led to the hypothesis that people with B blood group would be less susceptible to the disease, a hypothesis that was confirmed shortly afterwards.
Human red blood cells are coated by carbohydrate molecules which determine the blood type. Interestingly, the strains that have emerged more recently are able to bind to the three bloodgroups. The most prevalent norovirus strain in the world today is known as GII.4, which can recognize virtually any blood type. This suggests that pathogens can evolve to encompassing a broader host number.
As well as V. cholerae and noroviruses, additional pathogens are now regularly being identified that interact differently according to their hosts’ histo-blood group. These include Escherichia coli, rotaviruses and the dengue virus. Each pathogen attacks blood groups in slightly different ways, which means that in a world full of different infectious diseases, eradication of a single blood group is very unlikely to happen. Unless we find a way to conquer all the blood group-associating pathogens, we will have to keep checking blood types thoroughly prior to blood transfusions for millennia to come.
