Need for blood group typing went hand in hand with blood transfusions even as the latter has become embedded as an integral part of the practice of medicine since the early 20th century and yet function(s) of blood group antigens remain(s) unknown even >100 years after their discovery.
This answer briefly covers
- How presence of anti-blood group antibodies led to the discovery of blood group antigens.
- How blood group antigen distributions in native populations around the world are far from random and appear to be the result of intense selection pressure.
- Resistance to prominent infections prevalent in different parts of the world may have favored some blood groups over others. Bottlenecks, founder effects, genetic drift, natural selection likely played a role as well.
- More recent studies explore whether blood group antigens help shape gut microbiota composition.
Anti-blood group antibodies uncovered the existence of blood group antigens
Anti-blood group antibodies are the product of mismatched blood transfusions which result in severe transfusion reactions. Such reactions uncovered the very existence of blood group antigens.
While blood transfusions had been tried through history, severe transfusion reactions impeded their utility and they only became a safe procedure after Karl Landsteiner in 1901 discovered ABO blood group antigens (now more accurately called histo-blood group since epithelial and endothelial cells also express these antigens and many humans can also secrete them) and Reuben Ottenberg in 1907 suggested matching donor and recipient for ABO blood groups. WWI spurred development of blood banks as also the discovery and use of anticoagulants, both helping establish large-scale use of blood transfusions.
Possible functions of blood group antigens
Having evolved millions of years ago, blood group antigens are found in non-human primates such as chimpanzees, gorillas, gibbons as well. Obviously they serve some important biological function and don’t exist merely to induce antibodies against themselves in people who happen to get mismatched blood transfusions. However, even >100 hundred years later, we are still unclear about their function and therein lies the rub. Two sets of inter-related observations provide basis for the idea they may have extremely important roles,
- ABO and other blood groups have distinct geographic distribution patterns among native human populations suggesting they are under intense selection pressure (1; below from 2).
- What could such selection pressures be? A mound of data steadily building up over decades suggests that blood group antigens may differentially enhance resistance or susceptibility to infections (below from 3).
Cholera and malaria provide a couple of illustrative examples.
Areas of Bangladesh subject to severe cholera tend to have quite low type O but quite high type B (4). Turns out the cholera toxin secreted by Vibrio cholerae binds much more strongly to type O’s sugar molecule than to that of B’s (5; below from 6).
On the other hand, type O tends to be high in regions with high levels of severe falciparum malaria (below from 7). Malaria parasites may have greater difficulty sticking to type O red blood cells, which may confer survival advantage to individuals with that blood group in malaria-endemic regions.
Now in the age of microbiota, some studies even suggest that blood group antigens may help shape gut microbiota composition (8, 9) though others suggest otherwise (10), leaving this possibility as yet open-ended.
Bibliography
1. Blood type distribution by country – Wikipedia
2. Distribution of Blood Types
3. Eder, A. Frattali, and S. L. Spitalnik. “Blood group antigens as receptors for pathogens.” Molecular biology and evolution of blood group and MHC antigens in primates. Springer, Berlin, Heidelberg, 1997. 268-304. https://www.researchgate.net/pro…
4. Glass, Roger I., et al. “Predisposition for cholera of individuals with O blood group possible evolutionary significance.” American journal of epidemiology 121.6 (1985): 791-796.
5. Vasile, Francesca, et al. “Comprehensive analysis of blood group antigen binding to classical and El Tor cholera toxin B-pentamers by NMR.” Glycobiology 24.8 (2014): 766-778.
6. Heggelund, Julie Elisabeth, et al. “High-resolution crystal structures elucidate the molecular basis of cholera blood group dependence.” PLoS Pathogens 12.4 (2016): e1005567. High-Resolution Crystal Structures Elucidate the Molecular Basis of Cholera Blood Group Dependence
7. Cserti, Christine M., and Walter H. Dzik. “The ABO blood group system and Plasmodium falciparum malaria.” Blood 110.7 (2007): 2250-2258. The ABO blood group system and Plasmodium falciparum malaria
8. Kashyap, Purna C., et al. “Genetically dictated change in host mucus carbohydrate landscape exerts a diet-dependent effect on the gut microbiota.” Proceedings of the National Academy of Sciences 110.42 (2013): 17059-17064. http://www.pnas.org/content/pnas…
9. Gampa, Anuhya, et al. “Relationships between gastrointestinal microbiota and blood group antigens.” Physiological genomics 49.9 (2017): 473-483. https://www.physiology.org/doi/p…
10. Davenport, Emily R., et al. “ABO antigen and secretor statuses are not associated with gut microbiota composition in 1,500 twins.” BMC genomics 17.1 (2016): 941. ABO antigen and secretor statuses are not associated with gut microbiota composition in 1,500 twins