Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology
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4-1 BB, a member of the tumour necrosis factor receptor superfamily, functions as a co-stimulatory molecule. Recently, stimulation of the 4-1 BB pathway was shown to suppress antigen-specific CD4(+) T cell and subsequent T cell-dependent humoral immune responses. ⋯ These results suggest that stimulation of the 4-1 BB pathway effectively suppresses some features of allergic asthma, including allergen-specific IgE production and AHR, through deletion of allergen-specific Th2 cells. However, we found that bronchial allergic inflammation was not strictly mediated by suppression of the Th2 immune response in this murine model of asthma. Despite these somewhat contradictory effects, intervention in the 4-1 BB pathway might provide a potential novel immunotherapeutic approach for treatment of allergic asthma.
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Empynase is a proteolytic enzyme that is widely used as an anti-inflammatory drug in Korea. We evaluated the prevalence of sensitization to Empynase in association with respiratory allergy symptoms in exposed hospital personnel, and identified the IgE-binding components in the Empynase extract, using sera with high levels of specific IgE antibodies. ⋯ Forty-two subjects (27.3%) complained of work-related respiratory symptoms (WRRS). Five nurses (3.7%) and one pharmacist (5.3%) had work-related asthma symptoms, and 34 nurses (25.2%) and six pharmacists (31.6%) had work-related rhinitis symptoms. The prevalence of sensitization to Empynase on SPTs was 20.1%, and tended to be higher in pharmacists (31.6%) than in nurses (18.5%). It was estimated that 3.9-8.4% of hospital personnel had WRRS attributable to Empynase. The duration of exposure was longer in positive SPT responders than in negative responders (51.9+/-27.5 vs. 39.2+/-27.3 months, respectively; P<0.05), and the prevalence of Empynase-positive SPTs was significantly higher in subjects with asthma than in those without asthma (57.1% vs. 18.4%, respectively; P<0.05). The levels of Empynase-specific IgE antibodies were significantly higher in pharmacists (76.1+/-83.4 OD units) and nurses (56.3+/-103.0 OD units) than in normal controls (39.8+/-12.7 OD units; P<0.05). Seven subjects (two pharmacists and five nurses) had high serum levels of Empynase-specific IgE antibodies; six of these subjects had WRRS. ELISA inhibition tests were performed with the sera of these six subjects, revealing significant inhibition only with the addition of Empynase. Four strongly staining protein bands (sizes: 36, 33, 16, and 10 kDa) from Empynase extract were observed to bind to the IgE antibodies of sensitized subjects. Conclusion Exposure to Empynase powder may cause rhinitis and asthma in hospital personnel, and the pathogenic mechanism appears to be IgE mediated.