Washington: Scientists have identified the histamine releasing factor (HRF) molecule as a promising target for developing new treatments for a number of allergic reactions including asthma.
In the new study, Toshiaki Kawakami and his team of researchers from La Jolla Institute for Allergy and Immunology point to the development of new therapies based on blocking HRF interactions with certain antibody (IgE) molecules, long known to be central causes of allergies.
The study has also found two novel peptides (N19 and H3) as strong therapeutic candidates for blocking the HRF and IgE interactions. Peptides are protein pieces that spur various molecular actions.
The two peptides inhibit the interactions of the HRF and IgE molecules, thereby stopping the allergic cascade in mouse models.
“Based on our preliminary studies, we believe these HRF inhibitors may provide a new, innovative therapeutic avenue for the treatment of asthma and some allergies,” Kawakami said.
According to Hannah Gould, a professor and prominent allergy researcher at King’s College in London, the study advanced scientific understanding in several key ways.
“The research community has long believed that the histamine releasing factor (HRF) played some role in triggering allergic responses and asthma in certain individuals,” she said.
“However, the identity of the primary binding partner, the HRF receptor, the unique characteristics of the IgE in these individuals, and the mechanisms involved in HRF activity have remained elusive until the present study by Dr. Kawakami and his team.
“These findings suggest a potential treatment for allergy and asthma patients who have HRF reactive IgE.
“We can look forward to the future results of pre-clinical and clinical studies in the human system,” Gould said.
Kawakami said the HRF molecule has been studied for many years and was thought to play some role in the cellular interactions leading to allergies and asthmas. However, its exact purpose and mode of operation was previously not clear.
“Nasal drainage, skin blister fluids, and some bronchial fluids were found to contain HRF secretions, so the scientific community suspected that HRF was important, but we didn’t know why,” Kawakami said.
HRF studies had been limited by several factors over the years, he added, including the inability to model HRF interactions in mice. In addition, Kawakami said failure to identify the HRF receptor also slowed progress.
“It’s very, very unusual for many years to pass between the discovery of a molecule and the identification of its receptor,” he said. “In this case, 15 years had passed. Without the receptor, we couldn’t understand the role of this protein in asthma and allergies,” he said.
Kawakami and his team were the first to solve this mystery in 2007 -- identifying a subset of IgE and IgG molecules as HRF receptors. This information gave his group the critical missing piece of the HRF puzzle and enabled the researchers to map HRF’s role in allergy activation.
The study has been recently published online in the Journal of Clinical Investigation.