Transforming Blood Transfusions

Blood is essential. It carries the oxygen you breathe throughout your body and to your lungs, keeping you alive and invigorated. However, our body can only produce so much blood in a day, and when we undergo serious blood loss through car accidents, genetic disorders, or surgeries, we need to replenish our body’s blood supply. People around the world donate their blood to those who are in desperate need and each year, 4.5 million lives are saved thanks to blood donations.

The transfer of one person’s blood to another person’s body is called transfusion, and in the United States alone, someone needs a transfusion every two seconds1. Currently, blood transfusions are limited by the type of blood one has – and therefore needs. Blood has four major types: ‘A’, ‘B’, ‘AB’, and ‘O’, and each of these major types has two subtypes, positive or negative. This means there are a total of eight blood types: A+, A-, B+, B-, AB+, AB-, O+, O-. These types are determined by different molecules called antigens (you can think of them as tags or signs) on the outside of the blood cell (see image below, different blood types have different molecular patterns or “tags”). 

The four major blood types are defined by the antigens, or “tags”, on their surfaces. The “H” antigen of blood type “O” is the most common, and can be converted by enzymes to “A” or “B” antigens. If you don’t have “A” or “B” blood types, it is because you don’t have the enzymes that can convert antigen “H” to the other antigen types.

Blood transfusions are limited by these specific antigens (tags) because the antigens are recognized by a person’s immune system or, the body’s defense system. If you have blood type “B”, and now have blood type “A” in your body, due to a transfusion, your immune system will recognize that “A” is not part of your body, and will trigger an immune response which attacks and destroys the blood that has been transfused.

A group from the University of British Columbia in Canada identified a bacterium in the human stomach that can convert blood type ‘A’ to the universal donor type, ‘O’2. By screening thousands of microbes in our stomachs, the scientists identified a particular obligate anaerobe (can only survive when oxygen is not present), Flavonifractor plautii. Inside F. plautii, two enzymes were found to work together to change the molecules on the surface of red blood cells of blood type ‘A’ to molecules of blood type ‘O’.

But how can blood types be changed from one blood type to another? 

Below is a diagram of blood type ‘A’ and blood type ‘O’. They have some “tags” in common (the blue squares, orange circles, and grey diamonds), and some that differ (green pentagon). The enzymes in F. plautii are able to cut off the extra molecular tag of blood type ‘A’, which then leaves blood type ‘O’! First, the enzyme FpGalNAcDeAc changes the ‘A’ blood type molecules to a slightly different molecule, which can then be recognized and cut by the second enzyme, FpGalNase, leaving blood type ‘O’. Not only can these enzymes change blood type ‘A’ to ‘O’, but they can do it fairly efficiently, which could greatly increase the blood supply for transfusions. 

Blood Type “A” to Blood Type “O” Conversion Pathway. FpGalNAcDeAc enzyme recognizes the “A” antigen, and changes it to a different molecule. This new molecule is recognized and removed by FpGalNase, leaving only the “H” antigen which characterizes blood type “O”.

The group from British Columbia are not the first to try changing blood type3. A previous study converted blood type ‘B’ to blood type ‘O’, albeit very inefficiently. So inefficiently, in fact, that the conversion would never have practical use4

Since the enzymes from F. plautii are bacterial, and only small amounts of the enzymes are needed for conversion of blood type ‘A’ to blood type ‘O’, it could be possible to mass produce the enzymes to be able to transform large quantities of blood for transfusions, increasing blood supply for medical procedures and saving more lives.

Sources:

  1. https://www.redcrossblood.org/donate-blood/blood-types.html
  2. Rahfeld, P., Sim, L., Moon, H., Constantinescu, I., Morgan-Lang, C., Hallam, S. J., Kizhakkedathu, J. N., and Withers, S. G. (2019) An enzymatic pathway in the human gut microbiome that converts A to universal O type blood. Nat. Microbiol. 10.1038/s41564-019-0469-7
  3. Goldstein, J., Siviglia, G., Hurst, R., Lenny, L. & Reich, L. Group-B erythrocytes enzymatically converted to Group-O survive normally in A, B, and O individuals. Science 215, 168–170 (1982).
  4. Kruskall, M. S. et al. Transfusion to blood group A and O patients of group B RBCs that have been enzymatically converted to group O. Transfusion 40, 1290–1298 (2000).

Peer edited by Abigail Agoglia

Will dogs save us from allergies?

https://www.flickr.com/photos/tomsaint/16730323546

Picture from: Rennett Stowe

Dog is man’s best friend. Man is dog’s…predictor for allergies?

A recent study showed dogs with owners that suffer from allergies are more likely to suffer from allergies themselves. Researchers also found that dogs that live in urban environments are more likely to have allergies than dogs in rural environments. The same correlation between urban environments and allergies is found in humans. Humans in rural environments come in contact with more species of microbes than their urban counterparts. It is thought that contact with many microbes early in life may protect humans from developing allergies. The same phenomenon is thought to occur in dogs. It appears man and man’s best friend have more in common than originally thought.

Allergies in humans and dogs have been on the rise in the western world. There have been many studies to look at the causes of these allergies in humans, but few have looked into the causes in dogs. Researchers at the University of Helsinki in Finland wanted to change this. We already know that humans who live in urban environments are more likely to have allergies than human who live in rural environments. Hakanen and colleagues wanted to know if the same is true in dogs.

Researchers sent surveys to almost 6000 dog-owners in Finland. The survey asked questions about the dog’s breed, the dog’s current environment (urban v. rural), the dog’s environment at birth, the dog’s allergies, and the owner’s allergies. When analyzing the data, they removed dog breeds known to be genetically prone to allergies, so they could focus on environmental factors. After compiling the data, Hakanen et. al. concluded that dogs who live in urban environments are more likely to have allergies than their rural counterparts. It is important to note, the data are influenced by how much time the dog spends outside and how much contact the dog has with farm animals. Strangely, living in larger human families can also protect dogs from developing allergies. This suggests that we might protect our dogs from allergies; similar to the way they protect us from developing allergies.

https://www.flickr.com/photos/dani0010/537522266

Allergy symptoms in dogs can include itchiness, sneezing, hives, constant licking, itchy ears, and itchy, runny eyes. Picture from: Dani

Researchers cannot be certain the cause for differences in allergies between urban dogs and rural dogs and dogs in smaller vs. larger families, but they do have some theories. In humans, the microbiota, or the microbes that live in our bodies and do not cause illness, are an important factor in allergy development. It is thought that humans who grow up in rural areas come in contact with and are colonized with environmental microbes that protect people from allergies. The microbiota is also thought to be important for development of allergies in dogs. Dogs living in rural environments may come into contact with more environmental microbes that protect them from allergies. Furthermore, dogs in larger families likely come into contact with more species of microbes because each family member harbors a unique microbiota.

Though many of the study’s findings are similar between dogs and humans, one difference between human and dog allergies seems to be the impact of birthplace. A dog’s birthplace is not a predictor for allergies in dogs like it is in humans. Researchers think a dog’s birthplace may be less important because dogs are usually removed from their birth environment fairly early (7-8 weeks), when compared to humans (18yrs).

Hakanen and colleagues were able to identify multiple environmental factors important for predicting if a dog will develop allergies. However, the most striking finding of the study was actually in the dog owners. Dogs with owners that have allergies are more likely to have allergies. Though this is not a new finding, it suggests that the factors important to developing allergies in humans and dogs may be the same. The idea that the same factors could influence allergy development in both dogs and humans is particularly intriguing considering dogs suffer mostly skin and food allergies and few respiratory symptoms. Respiratory symptoms from pollen allergies are among the most common in humans. Furthermore, the immune responses that cause allergic symptoms in dogs and humans are different. This suggests the factors influencing allergy development may be important for all mammals despite differences in their immune systems.

There is still more research to be done to determine the factors that lead to allergies in dogs and humans. However, the studies of Hakanen et. al. and others suggest that if we can determine the factors important for developing allergies in dogs, for which it is easier to gather environmental and health information, we may be able to apply these findings to humans. So in addition to being the best listeners, best cuddlers, and our best friends, dogs may just be our best chance to cure our allergies.

Peer edited by Christina Parker

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