Novel solution for deadly allergies

Researchers at the Australian National University (ANU) have discovered a function in the immune system that could hold the key to treating allergic conditions like asthma and stop life-threatening anaphylaxis. The process is driven by a protein in the body called neuritin.

“We found this absolutely fascinating mechanism of our own bodies that stops the production of rogue antibodies that can cause either autoimmunity or allergies,” says ANU’s Professor Carola Vinuesa, a senior author of the study.

“It’s been known for years that neuritin has a role in the brain and in the nervous system but we found an abundance of neuritin in the immune system and its mechanism – which has never been described in biology.”

The findings, published in Cell, could potentially revolutionise treatments for a host of health problems.

“[The discovery] is very timely precisely because allergies and autoimmune diseases are on the rise,” says Dr Paula Gonzalez-Figueroa, the study’s lead author. “It is predicted that 1 in 3 people will suffer from some form of allergy and up to 8% of Australians suffer from an autoimmune disease.

“There are several theories backed up by data that suggest that a population less exposed to infections, together with changes in diet that can impact the good bacteria in the gut, can all contribute to the increase in allergies and autoimmune diseases.”

Paula gonzalez figueroa and carola vinuesa credit jamie kidston anu 1
Paula Gonzalez Figueroa and Carola Vinuesa. Credit: Jamie Kidston, ANU.

Neuritin is produced by follicular regulatory T cells (Tfr cells). For a long time neuritin’s function in the immune system wasn’t known – the new research shows it targets pathogenic B cells that produce the antibody Immunoglobulin E (IgE), which causes allergic reactions, and autoantibodies which drive autoimmune reactions.

Allergies occur when the immune system responds disproportionately to an allergen – like dust, animal hair, pollen – and produces IgE. IgE leads to the release of histamine, which can cause damaging and sometimes fatal reactions in the body, such as anaphylaxis.

The absence of neuritin, the study found, was connected to a higher risk of death by anaphylaxis; its use, then, may hold the key to saving lives and alleviating the often-debilitating symptoms of allergies.

Based on its B-cell suppressing capabilities, neuritin may also form the basis of new treatments for autoimmune diseases like lupus and rheumatoid arthritis.

“There are over 80 autoimmune diseases, in many of them we find antibodies that bind to our own tissues and attack us instead of targeting pathogens – viruses and bacteria,” Gonzalez-Figueroa says.

“We found neuritin supresses formation of rogue plasma cells, which are the cells that produce harmful antibodies.”

Credit: Gonzalez-Figueroa, et. al. 2021.

If the new findings lead to the development of neuritin-based therapies, autoimmune diseases may become treatable without the damaging side effects of extant therapies.

“Traditional therapies tend to dampen the entire immune system,” Gonzalez-Figueroa explains. “The newer therapies that have entered the market in the last few years also work through elimination of particular cells of the immune system or their products, which can leave patients more susceptible to infections.

“By contrast, neuritin would leave these components intact while reinforcing our natural mechanism of tolerance.”

The research is still in its infancy, with the new study based on observations in mice and human cells in vitro, but team members have high degree of confidence about the discovery.

“We are partnering with pharma to explore neuritin-based therapies and the possible use in autoimmunity and allergies,” Gonzalez-Figueroa says. “Because neuritin is a protein made by our own body, it is expected to be well tolerated. We hope that it might not take too long to reach clinical trials.”

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