Being able to simply turn off your allergies sounds like a dream鈥攂ut a new discovery shaking the foundations of allergy research might have just made that possible.
For the first time, researchers say, a team has isolated a cell responsible for remembering allergies and triggering the production of antibodies that cause the allergic reaction.
It鈥檚 a 鈥済round-breaking discovery,鈥 researchers say, which paves way for treatments that could potentially shut off an allergic response completely.
鈥淏efore the discovery of this cell, we didn't really know exactly what it was that we were trying to go after. And so now, basically, we have the smoking gun, we know this is the thing that is keeping people allergic,鈥 Josh Koenig, assistant professor with McMaster鈥檚 Department of Medicine and co-lead of the study, told CTVNews.ca in a phone interview Tuesday.
鈥淎nd our job now is to find ways to inactivate it.鈥
Researchers with McMaster University and Denmark-based pharmaceutical company ALK-Abello discovered that a type-2 memory B cell (MBC2) was making the antibodies found in allergic reactions. People without allergies had very few memory B cells, if any, researchers found.
B cells are one of the types of immune cells that work to protect our body during an immune response.
Prior to this research鈥檚 publication in the peer-reviewed journal Science Translational Medicine this Wednesday, this specific type of cell had never been described before, Koenig said, adding that their work is being published parallel to a second study confirming the presence of this cell in children with peanut allergies.
Allergies have always been a bit of an anomaly in the medical world, because it鈥檚 not a disease that is continually progressing and spurring a constant immune response, nor a chronic condition that needs ongoing management.
鈥淲ith allergies, people can avoid their food for a long time, but they still stay allergic, and how the immune system remembers how to stay allergic like that is something that's not well understood,鈥 Koenig said.
Researchers have been working on this puzzle for around 15 years, he said.
鈥淲e know that how the immune system works is every time it sees the allergen through, say, an accidental exposure, that the immune systems will wake up, and it will start making more of the thing that makes you allergic, which are antibodies. Antibodies make people allergic,鈥 Koenig said.
When a person with a serious shellfish allergy goes into anaphylactic shock after accidentally eating a piece of shrimp, the anaphylactic reaction is these IGE antibodies at work. But their production has to be triggered by another cell.
鈥淲e kind of started by wondering, 鈥榃ell, is there a type of cell that will hold this memory that will basically be the ones who contribute to that allergic antibody production? And the answer turned out to be yes.鈥
In order to find out whether there was a specific foot soldier among the memory B cells that was in charge of remembering allergies, researchers created a type of fluorescent molecule called, tetramers, out of allergens to locate memory B cells, building on previous research by Koenig and his team. They also used single cell sequencing, using computers to arrange more than 90,000 cells into groupings based on their physical similarities.
鈥淏asically, we took a bunch of B cells out of people's blood who are allergic,鈥 Koenig said. 鈥淎nd then we looked at every single cell and looked at all of the genes that that cell makes.鈥
A big portion of their data relied on clinical samples from ALK-Abello, which had a cohort of people taking an immunotherapy drug for their allergies.
鈥淏asically, they were taking a little bit of their allergen every single day,鈥 Koenig explained. 鈥淎nd in the first little while of taking that therapy, their immune system actually makes many more allergic antibodies.鈥
This allowed researchers to study the production of allergic antibodies without actively triggering dangerous allergic responses.
The immunotherapy drug addressed allergies to birch, a seasonal allergy, or allergies to dust, 鈥渟omething that鈥檚 common for asthmatics,鈥 Koenig said.
鈥淚n both of those contexts, we found those cells.鈥
Researchers also looked at people with peanut allergies, one of the most common food allergies. MBC2 was found to be producing antibodies in those people as well鈥攕uggesting this cell could be the culprit behind a wide scope of allergies.
鈥淲hat underlies these different conditions is the same thing,鈥 Koenig said. 鈥淎nd so how we're thinking about it is that basically any allergy that has these allergic antibodies鈥攚hich is pretty well all of them鈥攖hese are the ones that have these types of cells (MBC2).鈥
The implications are vast, researchers say.
If an allergic reaction is the destructive stampede caused by someone shouting 鈥榝ire鈥 in a packed auditorium, MBC2 is the person who yelled. It鈥檚 not the cause of the damage itself, but if it could be stopped from triggering the production of allergic antibodies, there would, theoretically, be no allergic reaction.
鈥淭he discovery really pinpoints two potential therapeutic approaches we might be able to take,鈥 Kelly Bruton, a postdoctoral fellow at Stanford University, said in a press release. Bruton co-led the research with Koenig when she was a PhD student at McMaster.
鈥淭he first is targeting those MBC2s and eliminating them from an allergic person. The other option could involve changing their function and have them do something that鈥檚 not going to be ultimately harmful when the individual is exposed to the allergen.鈥
Koenig said his colleagues are already working on understanding how to inactivate the cell, and that many other pharmaceutical companies will be able to come up with their own drugs that target this cell to shut it off without damaging the surrounding cells.
So will we start seeing medication that can shut off a peanut allergy on the shelves any day now? Not yet, Koenig says.
Ensuring the safety and efficacy of new drugs takes a long time, and so we鈥檙e looking a 鈥渁 minimum of five years鈥 to even understand how to apply this information into a drug and start the regulatory process.
鈥淚f there's stuff that ends up getting into these clinical trials from this work, that five to 10 year time point is possible,鈥 Koenig said. 鈥淥r if we need to make completely new things, it may be even longer than that.鈥
This research received funding from the Schroeder Allergy and Immunology Research Institute, Food Allergy Canada, ALK Abell贸 A/S, the Zych Family, the Satov Family, the Canadian Allergy Asthma and Immunology Foundation, and the Cancer Research Institute Irvington Postdoctoral Fellowship, according to the release.
There鈥檚 still a huge host of unanswered questions about allergies, Koenig said.
For instance, researchers don鈥檛 know what causes some allergic reactions to be so severe, or why the same person might have varying levels of severity in their allergic reactions over the span of their life.
We also still don鈥檛 know why the body produces MBC2 in the first place in people with allergies. The mistake likely happens even earlier, with the body seeing something it doesn鈥檛 recognize and then creating MBC2 in order to remember that the body is suspicious of a certain substance.
鈥淲e think that they are really mediators of this disease, or they're really the ones that are keeping people allergic in that long term,鈥 Koenig said. 鈥淗ow it emerges, how the cell comes to exist, is still a mystery that we need to figure out.鈥
But we don鈥檛 need to understand why the severity varies or why MBC2 emerges in order to target it for therapies.
鈥淭he really important thing is, before, we couldn't even see the horizon, didn't know what it was that we were trying to (target),鈥 Koenig said. 鈥淣ow, the horizon鈥檚 in view. And we know exactly where we need to go and what we need to do.鈥
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