Severe asthma poses significant risks, leading to numerous hospitalizations and emergency room visits annually, and even causing fatalities in the United States. To address this pressing issue, researchers at the La Jolla Institute for Immunology (LJI) conducted a study focused on understanding the molecular factors driving severe asthma and asthma exacerbation induced by rhinovirus. The findings, published in The Journal of Allergy and Clinical Immunology, suggest that inhibiting interactions between histamine-releasing factor (HRF) and immunoglobulin E (IgE) antibodies may benefit individuals with both types of asthma.
According to Professor Toshiaki Kawakami, the study’s lead researcher, many individuals with severe asthma do not respond well to current treatment options. Consequently, he and his team explored potential drug strategies that target HRF-IgE interactions as a means to alleviate symptoms for these patients. Kawakami expresses hope that this approach can offer effective treatment for severe asthma and asthma exacerbation.
The study focused on understanding how HRF, a molecular messenger produced by various cells including lung epithelial cells and macrophages, interacts with IgE antibodies, thereby triggering allergic reactions. The researchers discovered that HRF interactions with IgE antibodies drive harmful inflammation in mouse models of asthma. The team then investigated the role of HRF and IgE interactions in different patient groups, including healthy controls, individuals infected with rhinovirus, and those with varying degrees of asthma severity.
The results revealed that HRF and IgE interactions specifically contribute to inflammation in patients with severe asthma and rhinovirus-induced asthma exacerbation. These findings align with previous research conducted on mice. Additionally, laboratory experiments using human bronchial cells confirmed the significance of HRF and IgE interactions, as the secretion of HRF significantly increased when exposed to rhinovirus or common allergens like house dust mites.
Moving forward, Kawakami plans to test two potential therapeutic approaches. The first involves a molecule called HRF-2CA, developed by the Kawakami Lab, which has shown promise in alleviating asthma and severe food allergy symptoms in mice. The second approach focuses on studying a therapeutic antibody called SPF7-1, acting as an HRF decoy by binding to IgE and preventing interactions with HRF.
Kawakami emphasizes the importance of conducting clinical trials to further evaluate these therapeutic options and their efficacy in treating severe asthma.