La Jolla: Many people are unaware of the potential severity of asthma. Ten American deaths are attributed to asthma each day, along with 439,000 hospital admissions annually and 1.3 million visits to emergency departments.
"Asthma is one of the most important allergic diseases to study," said Professor Toshiaki Kawakami, M.D., Ph.D., a member of the Center for Autoimmunity and Inflammation at La Jolla Institute for Immunology (LJI).
Kawakami and his LJI coworkers have lately investigated the molecular basis of severe asthma and exacerbations of rhinovirus-induced asthma, a kind of asthma that can develop concurrently with a cold.
Their study, which was recently reported in The Journal of Allergy and Clinical Immunology, suggested that people with both types of asthma may benefit from therapies that avoid interactions between a molecule known as histamine-releasing factor (HRF) and antibodies known as immunoglobulin E (IgE), which are known as histamine-releasing factor (HRF) and histamine-releasing factor (HRF).
Many persons with severe asthma don't respond to the available treatments, as Kawakami says. He is hoping that two prospective medication development tactics from his group may block the interactions between HRF and IgE and provide these patients with relief.
"We hope this approach can be a means of treating severe asthma and asthma exacerbation," he said.
Immune cells work as a team, and they secrete molecules to "talk" to each other. One of these molecular messengers is HRF, which is made by many types of cells, including lung epithelial cells and immune cells called macrophages. When a person encounters an allergen, these cells start churning out more HRF. The HRF then courses through the body and looks for special antibodies to bind to. HRF has several different kinds of antibody partners, however, and each interaction sends a different message to the surrounding immune cells.
Kawakami and his colleagues are working to understand how these HRF and antibody interactions drive dangerous allergic reactions. Over the last decade, the researchers have shown that HRF interactions with the IgE antibody drive harmful inflammation in mouse models of asthma.
Their new study is important because it sheds light on how this same HRF and IgE interaction triggers inflammation and drives asthma in humans. For the study, Kawakami collaborated with clinicians and scientists at the University of Pittsburgh School of Medicine; Children's Hospital, Boston; and the University of Virginia to investigate the role of HRF across many patient groups.
Working with this large range of patient samples was critical. "Asthma isn't just one disease," Kawakami says. There are different forms of asthma, called "endotypes," and current asthma therapies don't work for all patients. Truly understanding and treating asthma means gathering data from every patient group possible.
The team found that HRF and IgE interactions drive inflammation specifically in patients with severe asthma and patients with rhinovirus-induced asthma exacerbation. These findings in humans are in line with the lab's previous findings in mice.
The scientists further confirmed the importance of HRF and IgE interactions in laboratory experiments using a line of human bronchial cells. Kawakami and his colleagues observed a dramatic increase in HRF secretion when they infected these cells with rhinovirus. They saw the same dramatic increase when they exposed the bronchial cells to proteins from house dust mites (a very common allergen and asthma trigger).
Kawakami now hopes to test two potential asthma therapies. The first therapeutic approach would harness a molecule developed by the Kawakami Lab. This molecule, termed HRF-2CA, appears to inhibit asthma and severe food allergy symptoms in mice, and there's reason to think they could help treat humans as well. (ANI)
