Patients with both severe asthma and rhinovirus-induced asthma exacerbation may benefit from therapies that block interactions between a molecule called histamine-releasing factor (HRF) and antibodies called immunoglobulin E (IgE), according to research published in The Journal of Allergy and Clinical Immunology.
Professor Toshiaki Kawakami, MD, PhD, of the Center for Autoimmunity and Inflammation at La Jolla Institute for Immunology (LJI) and LJI researchers examined HRF levels and IgE interactions in:
- healthy adult controls
- adults infected with rhinovirus
- adults with moderate asthma
- adults with severe asthma
- adults with mild to moderate asthma
- asthmatic children with non-viral asthma exacerbation
- asthmatic children with rhinovirus-induced asthma exacerbation
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 said people with severe asthma aren’t responsive to current asthma therapies. He hopes two potential drug strategies from his laboratory might inhibit HRF and IgE interactions and deliver relief for these patients. “We hope this approach can be a means of treating severe asthma and asthma exacerbation,” he says.
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.
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.
The researchers are also interested in studying a therapeutic antibody called SPF7-1, which acts as a sort of HRF decoy, binding to IgE and blocking interactions with the real HRF.
