Allergic Diseases - Hirohito Kita

Mechanisms of Chronic Rhinosinusitis

We are studying the mechanisms that chronically activate immune cells in patients with allergic disorders, such as asthma and chronic rhinosinusitis (CRS). This involves the responses of immune cells, such as lymphocytes and NK cells, to common environmental antigens in patients. We tested the blood cells involved in immunity from 18 patients with chronic rhinosinusitis and found that their cells showed exaggerated responses to the common airborne fungi, Alternaria alternata. Blood cells involved in immunity from 15 normal individuals did not respond. This anomalous response to ubiquitous environmental fungi might explain the persistent airway inflammation in chronic rhinosinusitis patients. We are also studying the pathologic mechanisms of eosinophils in human diseases in vivo. In particular, how does eosinophilia (extraordinary increases in eosinophil number) occur in patients, how do eosinophils infiltrate into the tissues, and how do eosinophils become activated in local inflammatory sites. In studying the role of fungal organisms in the development of airway inflammation with many eosinophils, we used an anti-fungal medication. This randomized, placebo-controlled, double-blind pilot treatment in chronic sinusitis patients used irrigation of the nose (twice a day) with an anti-fungal medication versus patients treated with placebo for six months. The patients treated with medication had less swelling in their nasal passages and reduced levels of a protein associated with eosinophils in their mucus. Also, biopsy specimens obtained during surgical treatment from chronic rhinosinusitis patients show clusters of eosinophils and eosinophil granule proteins in the mucus. (View image)

Eosinophils were not found in healthy normal control tissues and mucus. In the laboratory, eosinophils from healthy people do become activated and degranulate, when they are exposed to Alternaria (View images) or to one other fungus, Penicillium, but not to 5 other fungi. Preliminary analyses of the glycoproteins and other components in Alternaria and the biochemical response mechanisms shown by the eosinophils are also described. These results provide many new avenues to better understand the immunological responses by human cells and tissues to a common environmental fungus (View image) and to develop novel treatment strategies for patients.