Immunoregulatory Effect Of IRAK-M In Asthma And Clinical Characteristics Of Allergic Bronchopulmonary Aspergillosis Patients

Objective:This study is designed to investigate the effect of missing IRAK-M on Th2 inflammation of asthma, and its impact on dendritic cells, macrophages and CD4 + T cell function.Methods:1) Asthma model:acute and chronic persistent asthma model were establish by IRAK-M-/- and wild-type mice thrugh OVA-sensitization; IRAK-M in wild-type mice with asthma was evaluated by RT-PCR and immunohistochemistry; Airway hyperresponsiveness, serum total IgE, pulmonary pathology were measured by Spirometer, ELISA, HE stain respectively; BALF inflammatory cytokine detection, lung and spleen Th cell subsets, pulmonary alveolar macrophages and DC costimulatory molecules were detected by Flow Cytometry.2) In vitro cell experiments:Proliferation assay and differentiation assays were carried out by IRAK-M-/- and wild-type mice spleen naive CD4 + T cell (purified by MACS separation); Bone marrow cells from IRAK-M-/- and wild-type mice were differentiated into BMDM/BMDC cells, costimulatory molecules were detected by Flow Cytometry after stimulation with OVA and LPS; Co-culture experiments were carried out by BMDC/BMDM (after 24h OVA stimulation) of IRAK-M-/- and wild-type mice and naive CD4 + T cells, then detect the differention of these cells by Flow Cytometry.3) macrophage cell transplant experiment: IRAK-M-/- and wild-type BMDC/BMDM (after 24h OVA stimulation) were transplanted to wild-type mice by nasal instillation, then evaluate the degree of the inflammtion after the expoure to OVA aerosol.Results:1) IRAK-M was significantly elevated in the lung of asthma; Compare with wild type asthma mice, asthmatic airway hyperresponsiveness, lung infiltration of inflammatory cells, BALF inflammatory total number and percentage of eosinophils cells, the percentage of Th2 and Th17 cells, IL-4, IL-13 concentrations were significantly higher, while Treg was lower in IRAK-M-/- acute asthmatic mice.2) IRAK-M-/- mice acute asthmatic lung epithelial pro-inflammatory cytokine IL-33, TSLP significantly increased, while IL-25 was similar.3) Naive CD4 + T cells from IRAK-M-/- mice were prone to differentiate into Th17, while difficult into Treg reduced.4) Pro-inflammatory costimulatory molecules were increased in DC and macrophages of IRAK-M-/- acute asthmatic mice lung; IRAK-M deletions may cause upregulation of pro-inflammatory costimulatory molecules in BMDC/BMDM, promotion of naive CD4 + T cells into differentiation proinflammtory Th subsets.5) Asthma inflammation of mice receiving IRAK-M-/- BMDC/BMDM was aggravated than the control.Conclusion:IRAK-M were significantly elevated in lung of asthma, and lack of IRAK-M could aggravate asthma inflammation through affecting airway epithelial cells, CD4+T cells, DC cells and macrophages.Objective:To summarize the clinical features of allergic bronchopulmonary aspergillosis(ABPA) so that this disease can be diagnosed early and treated timely. Methods We retrospectively analyzed the clinical data of 77 patients who had been admitted to Peking Union Medical College Hospital from January 1996 to July 2015 with ABPA.Results:The average age of these 77 patients (38 men and 39 women) was (41.8±18.3) years.74 cases (96%) combined with bronchial asthma, while 3 patients (4%) with pulmonary cystic fibrosis. The main symptoms and signs of ABPA were chronic cough(100%), sputum production(97%), wheeze (86%),sputum plugs (25%), blood-stained sputum(18%), hemoptysis(9%), chest pain (9%); fever (47%), weight loss (30%), night sweat (12%). Labotory findings revealed that 87% of blood eosinophils absolute count increased, and 89% of anti-Aspergillus antigen-specific IgE,57% of specific IgG,88% of Aspergillus antigen skin test were positive. Pulmonary function were performed, and the rate of obstructive ventilation and diffusion dysfunction were 66%,65% respectively; 60% of the bronchodilatation test were positive. The most common CT findings from this cohort of patients were central bronchiectasis(81%), patchy infiltrations(79%), pleural thickening(47%), mediastinal adenopathy(35%), nodular opacities(25%), mucoid impaction(21%), fleeting infiltrations(35%).44 cases(58%) were misdiagnosed as tuberculosis, pneumonia, lung abscess, and lung cancer autoimmune diseases and others.Conclusions:ABPA usually was misdiagnosed, clinicians should take ABPA into consideration in the patients of asthma or pulmonary cystic fibrosis with wheeze, sputum plugs,elevated eosinophils central bronchiectasis, fleeting infiltrations.