ORLANDO, Fla. — Spring is supposed to be the season of rebirth and new beginnings, but anyone with seasonal allergies knows springtime can also be the season of congestion and irritation. While current allergy treatments focus on soothing allergy symptoms after they start, a promising new approach may be able to stop symptoms before they begin in the first place.
Conducted by a team at the University of Central Florida, this research may one day free countless people from common seasonal allergies. Up until now, the vast majority of research and therapies for allergic asthma have focused solely on targeting the inflammatory cytokines in the body that react to allergens, consequently leading to an overproduction of mucus, wheezing, and breathing issues.
Commonly prescribed drugs for allergies nowadays like Omalizumab, Dupilumab, Mepolizumab, and Reslizumab work to lower or block the various cytokines and antibodies responsible for this asthmatic response – but all of these medications are reactionary; they get to work after a patient’s airway inflammation is well underway.
So, Dr. Justine Tigno-Aranjuez set out to establish a new strategy for stopping allergen receptors from reacting in the first place. She chose a technique called LRC-TriCEPS, which works to identify receptors in cells, for a common allergen (house dust mite). That technology revealed a specific cell protein (LMAN1) that had never been implicated before as having a role in the body’s allergen response.
“When we first had this discovery, we wanted to know, ‘What is this protein? What is already known about LMAN1 as an allergen receptor?’ and the interesting thing was that people had not been paying much attention to this protein in the context of allergy or allergic asthma,” Tigno-Aranjuez says in a university release.
Prior to this discovery, LMAN1 had generally been known as a cargo receptor, or a protein responsible for moving other proteins inside and outside the cell. Dr. Tigno-Aranjuez has now demonstrated that house dust mite allergens and LMAN1 can bind together on the cell surface in order to incite the inflammatory or allergic reaction. These findings further highlight that the binding depended on specific mannose sugar structures on the house dust mite allergens. Since many other common allergens, including pollen and fungi, are mannosylated, or modified by the addition of mannose sugars, this work holds major potential.
“Our thinking is that this could potentially not just be restricted to dust mites because many other allergens are mannosylated, this could be a very broad receptor that recognizes many different allergens,” the study author explains. “If you are thinking in terms of potential therapy, by understanding how LMAN1 recognizes dust mites and the consequences of such recognition, you could apply this to many other settings, and that is what we are currently trying to explore.”
The National Institutes of Health recognized the tremendous potential of this UCF research, and just awarded Dr. Tigno-Aranjuez a $1.5 million R01 grant to investigate if LMAN1 has a role in the expression of other mannosylated allergens.
Dr. Tigno-Aranjuez’s research on LMAN1 was performed in collaboration with the Cleveland Clinic. Dr. Bin Zhang, Associate Professor at the Lerner Research Institute, served as a co-investigator on this study. Dr. Zhang is considered an expert in LMAN1.
“LMAN 1 has been largely known as a protein that is involved in transporting proteins from inside cells to the outside of cells,” explains Dr. Zhang. “This research is the first one to show an entirely new function of LMAN1, as a receptor to bring proteins, such as allergens, from outside of cells to the inside. This could open up a new pathway for treatment.”
There are hundreds of thousands of allergic asthma cases in the United States annually (and many, many more globally). These findings represent a real step forward toward helping all of those people.
“Asthma is so prevalent that sometimes, people think, ‘We’ve already got a lot of treatments, we’ve got it covered.’ The reality is that we could always use more options, we could always improve upon existing treatments.” Dr. Tigno-Aranjuez concludes. “Many treatments can only be prescribed if you meet certain clinical criteria, many treatments are cost prohibitive, many are not covered by insurance. So any new treatment we can put forth that could potentially be a more universal treatment would always be an advance.”
Dr Tigno-Aranjuez and her team are now conducting further research aimed at confirming their hypothesis that other mannosylated allergens, such as pollen, are also recognized by LMAN1. If this theory is proven true, it could have major implications for future therapies intended to treat some of the most common allergens.
The study is published in the journal Cell Reports.
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