Researchers at the La Jolla Institute for Allergy & Immunology have identified the histamine-releasing-factor (HRF) molecule as a promising target for developing new treatments for a number of allergic reactions including asthma. The research team is also the first to clarify the role of the HRF molecule in promoting asthma and some allergies, including identifying its receptor. Their findings appear in the Journal of Clinical Investigation.
"Importantly, this work advances both the understanding of how HRF contributes to susceptibility of certain individuals in developing allergic disease as well as begins to unravel the mechanisms involved," said Juan Rivera, MSc, PhD, deputy scientific director at the National Institute of Arthritis and Musculoskeletal and Skin Diseases, part of the National Institutes of Health (NIH). "What is most encouraging is the demonstration that the effect of HRF to enhance allergic responses can be blocked, thus suggesting the possibility of new therapeutic strategies in allergic diseases."
The study points 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 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.
Toshiaki Kawakami, MD, PhD, the study’s leader, 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 asthma. 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," said Kawakami.
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," said Kawakami. "In this case, 15 years had passed. Without the receptor, we couldn’t understand the role of this protein in asthma and allergies."
Source: La Jolla Institute for Allergy and Immunology