Blood Types and Producing Type O With Enzymes From Microbes
Importance of Blood Type in Transfusions
Blood transfusions can be life savers. Strict precautions must be followed when giving a recipient someone else’s blood, however. If the wrong blood types are combined, the results can be deadly. New research might lessen the risk significantly as well as increase the usefulness of transfusions by producing a helpful blood type. The researchers have discovered how to turn other blood types into type O. This type of blood can be safely given to many people and in some cases to everyone. The altered blood is not yet available for medical use, but it may be at some point.
The most important blood typing systems with respect to transfusions are the ABO blood group system and the Rh system. The latter system is based on the rhesus factor. The most useful blood type for transfusion is O negative (type O blood without the rhesus factor). This is known as the universal donor type because it can be given to all people.
Red blood cells (erythrocytes) transport oxygen to cells. Platelets (thrombocytes) help blood to clot when we're injured. White blood cells (leukocytes) are part of the immune system and fight invaders, including red blood cells of the wrong type. Formed elements are transported by the liquid part of blood, which is known as plasma.
The ABO Blood Group System
Human blood exists as four major types: A, B, AB, and O. The designations are based on the identity of antigens on the cell membranes of red blood cells, or erythrocytes. An “antigen” is defined as a substance that’s capable of triggering a response from the immune system. The relevant erythrocyte antigens with respect to blood transfusions are designated as A and B.
- Type A blood has the A antigen.
- Type B blood has the B antigen.
- Type AB blood has both the A and the B antigen.
- Type O blood has neither antigen.
The immune system produces proteins called antibodies to attack antigens and the cells that bear them. A person makes antibodies that will attack invading blood of the wrong kind.
- Someone with type A blood makes antibodies that attack B antigens (but not ones that attack A antigens, or the person’s immune system would destroy their own erythrocytes).
- Someone with type B blood makes antibodies that attack A antigens.
- Someone with type AB blood makes neither antibody.
- Someone with type O blood makes both antibodies.
The table and illustration below summarize the ABO blood group system.
Antigens on Erythrocytes
Antibodies in Plasma
A and B
anti-A and anti-B
The Rh Blood Group System
The rhesus factor is another antigen on red blood cells. The term "rhesus" is considered obsolete by some investigators, who prefer the use of Rh. About 85% of the United States population has the rhesus antigen and is said to be Rh+. People without the antigen are said to be Rh-. Although the terms rhesus factor and rhesus antigen are generally used in the singular, they actually refer to a group of related antigens. The most common member of the group is the D antigen. When someone is said to be Rh-, it usually means that they lack the D antigen.
In an emergency, if type O- blood is unavailable, type O+ blood may be used as a universal donor blood type and given to Rh- people (as well as Rh+ ones). This is possible because unlike the case in the ABO system, an Rh- person doesn't make antibodies to the rhesus antigen until sensitization occurs. This isn't a rapid process and requires repeated exposure to the antigen. Receiving the O+ blood puts a patient one step closer to sensitization, however. The same point applies if they are given another type of Rh+ blood.
The distribution of blood types depends on ethnicity and the gene frequency in a population. AB- is the rarest type in the United States and O+ is the most common.
Universal Recipient and Donor
A person with type AB+ blood is said to be a universal recipient with respect to blood transfusions. They can receive any type of blood in a transfusion because they make no antibodies to attack it.
Someone with type O- blood is said to be a universal donor. Since their erythrocytes lack A and B antigens as well as the rhesus factor, their blood won’t trigger any recipient’s immune system and can be given to everyone. Type O- blood is the most useful type to have in a blood bank. Universal donor blood is very helpful in an emergency when there isn't time to determine the patient's blood type or where the technique is unavailable.
Donated blood may contain a low concentration of antibodies that could potentially attack a recipient's blood. The probability depends on how the donor's blood is processed at the blood bank and the form in which it's given to a patient (whole blood, red blood cells, platelets, plasma, or blood components). Any antibodies in the donation are generally diluted by the recipient's blood. This may make them insignificant, especially in an adult's body. In some cases, however, doctors do prefer to give a recipient exactly the same type of blood that exists in their body.
ABO Incompatibilty During Transfusions
An incompatibility reaction can occur when a recipient is given the wrong blood type. Possible symptoms of ABO incompatibility include the following:
- chest and/or back pain
- difficulty in breathing
- rapid pulse
- a feeling of impending doom
- blood in the urine
- jaundice (the appearance of a yellow colour in the skin and the whites of the eyes)
Incompatibility reactions are uncommon in many places because medical staff are well aware of the problems that can occur by mixing the wrong blood types and follow careful procedures. Mistakes occasionally happen, however. If a mistake is made, the patient needs to be treated right away. If the treatment is prompt and correct, the patient will probably recover. If prompt or correct treatment isn't provided, the patient may experience kidney failure and may not recover.
Red Blood Cell Antigen Structure
As shown in the illustration above, blood cells have chains of sugar molecules attached to their surface. (In science, the word "sugar" refers to additional chemicals besides the one that we use as a food sweetener.) The chains attached to type O cells aren't antigenic. The other cells have extra sugar molecules attached to their chains, which transforms them into antigens.
- Type A cells have N-acetylgalactosamine attached to the chain of sugar molecules.
- Type B cells have galactose attached to the chain.
- Type AB cells have chains with both attachments.
- Type O cells have chains with neither attachment.
Scientists want to remove the extra sugars from the chains, thereby converting all of the cells to type O ones.
Enzymes and Antigens: A Brief History
A "universal" blood type in blood banks would end incompatibility reactions. It would also allow the banks to make the best use of donated blood when the supply is low. Blood blanks often make an appeal for new donations. Maintaining a suitable stock of blood that is useful for everyone seems to be a problem. Enzymes that digest erythrocyte antigens might be very helpful.
Scientists have been studying how to modify the antigens of red blood cells for a long time. In the 1980s, researchers from the United States discovered that an enzyme from green coffee beans could remove the B antigen from blood cells.
In 2007, Danish researchers found that an enzyme from a gut bacterium called Bacteroides fragilis could remove the B antigen. In addition, they discovered that an enzyme from Elizabethkingia meningosepticum (or meningoseptica) was able to remove the A antigen. The Danish researchers said that their enzymes were more efficient than previous ones. The enzyme from B. fragilis was reportedly used up at one-thousandth the rate of the coffee bean enzyme, for example.
In 2015, UBC researchers obtained a useful enzyme from a bacterium named Streptococcus pneumoniae. The enzyme was able to remove red blood cell antigens. Enzymes are a type of protein. Like all proteins, they are made of amino acids. The order of the various amino acids and the shape of the molecule determine the identity of the protein. The researchers changed the order of the amino acids in the bacterial enzyme five times until they had created a molecule that digested the greatest number of antigens.
The discoveries described above show that the antigens of erythrocytes can be removed. None of the enzymes have become available in blood banks yet, however. The ones found by the Danish scientists sound intriguing, but I've seen no reports about them that were published more recently than 2007. A new discovery reported in 2018 seems hopeful, however. It's described below.
A Recent Discovery at UBC in Vancouver
In order to be medically useful, an enzyme must destroy all of the relevant antigens on all of the erythrocytes in donated blood. If any antigens remain in the blood, they will activate the recipient's immune system. In addition, the process must be efficient. A small amount of enzyme must produce a big result. A recent discovery at the University of British Columbia may be a major step towards these goals.
The UBC scientists have discovered how to transform another blood type into type O with thirty times more effectiveness than previous methods. The scientists used metagenomics in their search for useful enzymes. Metagenomics is the study of genetic material in the microorganisms found in a particular environment. A range of specialized and automated devices helps scientists to perform their analysis. The devices enable researchers to analyze millions of genetic samples relatively quickly.
The researchers examined DNA obtained from both the external environment and the environment in the human gut. They identified bacteria that feed on sugars found on the cells of the gut lining. These sugars are similar in structure to the molecules in the antigens on erythrocytes. The scientists found and isolated the digestive enzymes used by the bacteria. They then found that the enzymes could not only digest the antigens on the surface of red blood cells but also belonged to a new family of enzymes. The enzymes were also far more effective than previous antigen-digesting ones that have been discovered.
All of the research described in this article has been concerned with removing A and B antigens. It hasn't dealt with removing rhesus ones.
“We have been particularly interested in enzymes that allow us to remove the A or B antigens from red blood cells,” Stephen Withers, Ph.D., says. “If you can remove those antigens, which are just simple sugars, then you can convert A or B to O blood.”— American Chemical Society (2018 report)
Blood Transfusions in the Future
The UBC research seems to be progressing well but isn't ready to use clinically yet. One complication is that different subtypes of type A and type B blood exist. An enzyme (or multiple enzymes) must be able to deal with all of the subtypes. Another problem is that at the moment the engineered enzyme removes the majority of the N-acetygalactosamine molecules but not all them. The efficiency of the process needs to be improved.
Before transfusions with the altered blood become a reality, we need to know whether the red blood cells with antigens removed behave normally in the body. In addition, the process must be efficient. The use of a huge quantity of enzyme to treat a small quantity of blood wouldn't be practical. All of the digestive enzyme must be removed before the blood enters the body of the recipient.
The UBC researchers plan to hold larger tests on the enzymes that they've discovered. Eventually, they hope to perform clinical trials. They must demonstrate both safety and effectiveness before they do this. The end result could be the availability of a very useful process. The researchers may also learn more about human biology as they study and manipulate the blood cells, which would be another useful outcome of their research.
- Information about blood type from the American Red Cross
- ABO incompatibility from the U.S. National Library of Medicine
- Acute hemolytic transfusion reaction from the Australian Red Cross
- Antigen structure on the surface of red blood cells from ChemViews magazine
- Enzymes that can convert blood to type O from New Scientist
- Gut enzymes could hold key to producing universal blood from the University of British Columbia
- Making universal blood through enzymes from UBC
- Gut bacteria and universal blood from the American Chemical Society
Questions & Answers
Won't all these manipulations of blood types from microbes have side effects?
They may. On the other hand, they may be very helpful. A lot of research is required before the altered blood cells are used. They aren't ready to use in humans yet and may not be for some time.Helpful 3
© 2018 Linda Crampton