This post first appeared on Canadian Blood Services blog, written by Michelle Hampson

When a person is in dire need of blood, a blood transfusion seems like a simple solution. A donor donates blood, and eventually a patient in need receives it. Yet, in reality this life-saving medical procedure, as safe as it may be, is not that simple.

“There are people in the world that have such unique blood cells in terms of their antigens, or lack of antigens, that we cannot find compatible blood for them. These individuals, if they become sick or injured, they are at a much greater risk of dying simply because blood banks don’t have blood to give to them,” explains Dr. Scott. “And this is where stealth blood cells can come into play.”

Researchers have developed a technique that could make blood transfusions around the world much safer and more accessible, regardless of a donor or recipient’s blood type. By “chemically gluing” one simple compound to the blood cells, researchers can create stealth red bloods cells that can trick the immune system. These cells can easily hide from the immune system, undetected.

The compound is called methoxypolyethylene glycol (mPEG). It is very common, found in food and a variety of medicines, and therefore most peoples’ immune systems tolerate it. When an mPEG molecule is “glued” to a red blood cell, it works in two ways to escape immune cells that may seek to destroy it.

While most other molecules that could sit on the surface of a cell are rigid, mPEG is very flexible. This flexibility allows the molecule to flail randomly in every direction, creating a physical barrier between the red blood cell and any immune cells that approach it.

As well, many immune cells detect foreign cells based on the positive and negative charges of its antigens. Immune cells use these different charges and their distribution to identify each cell (similar to how fingerprints are used to identify individual people), as well as to bind to the cell. But mPEG is neutrally charged, allowing red blood cells with the molecule to evade detection from immune cells.

Pioneering the discovery of stealth red cells

Dr. Mark Scott is a senior scientist with Canadian Blood Services and an investigator at the Centre for Blood Research at the University of British Columbia. He is also a pioneer of stealth red blood cells. He first came across PEGylated compounds many years ago. Upon noticing how gluing mPEG to an enzyme helped it evade the immune system, he wondered if the same thing could happen with PEGylated red blood cells.

In his first study exploring PEGylated red blood cells, Dr. Scott and his colleagues found that adding the compound to red blood cells did not affect their structure, and their ability to carry oxygen remained within the normal range. They injected PEGylated red blood cells from humans into mice, and the mice did not experience an immune response to the foreign blood.

If stealth red blood cells offer similar benefits in humans, the implications could be huge for thousands of people around the world.

People with rare blood types and unique antigens are not the only ones who could benefit from this technology. A number of diseases, such as thalassemia or sickle cell anemia, require patients to undergo blood transfusions quite frequently, sometimes as often as 30 times per year.

Dr. Scott notes that these patients who receive chronic transfusions are the most likely to benefit from stealth red blood cells. “Because they receive so much blood, their immune system has a much higher exposure the foreign blood antigens, and is much more likely to somewhere along the line suddenly go – hey, you’re not normal, I don’t like you, and I’m going to make an antibody against you.”

For example, a study in 2013 found that 58 per cent of sickle cell anemia patients who received chronic blood transfusions became alloimmunized, which makes subsequent transfusions problematic.

Next steps in fooling the immune system…

Now Dr. Scott and his team are collecting antibodies from a diverse group of people in the hopes of mapping out how effective PEGylated red blood cells are for different blood groups.

Since studying mPEG as an effective compound for camouflaging red blood cells, Dr. Scott and his team have expanded their work to camouflage white blood cells, those of the immune system.

The results are remarkable. Normally, when you put white blood cells from two different people in a test tube together, the cells will proliferate like crazy, generating more immune cells in order to wipe out the other “foreign” cells. The immune reaction turns into a type of warfare. But in a study by Dr. Scott and his colleagues, when one “side” of white blood cells was PEGylated this arms race and attack on one another did not occur.  Videos at the microscopic level reveal that PEGylation decreases the number of interactions between the two opposing white blood cells.

“In one of the movies where we have one of the populations PEGylated, you see that the white blood cells don’t interact with each other. So we’re camouflaging the cells to the point that neither population realizes the other population is different and is there,” Dr. Scott says.

What’s more, adding a third strain of white blood cells in live mice, even though this strain was not PEGylated, did not cause an immune response. It seems that the presence of the PEGylated white blood cells allowed the immune system of the mouse to become accustomed to foreign blood cells. “So what we’ve done is we’ve induced tolerance in the blood recipient,” Dr. Scott explains.

Modifying white blood cells could not only help people who need blood transfusions, but people who need other tissue transplants as well. (Blood transfusion is technically a type of tissue transplant).

Although more research is needed before stealth red blood cells are tested in humans, the initial data suggest an intriguing way to avoid the negative reactions that can occur with blood transfusions and make the process much simpler – no matter how complex a person’s blood may be.