The Prostaglandin D2 Receptor CRTH2 Contributes to Airway Hyperresponsiveness during Airway Inflammation Induced by Sensitization without an Adjuvant in Mice.

INTRODUCTION: Prostaglandin D2 (PGD2), which is produced mainly by Th2 cells and mast cells, promotes a type-2 immune response by activating Th2 cells, mast cells, eosinophils, and group 2 innate lymphoid cells (ILC2s) via its receptor, chemoattractant receptor-homologous molecules on Th2 cells (CRTH2). However, the role of CRTH2 in models of airway inflammation induced by sensitization without adjuvants, in which both IgE and mast cells may play major roles, remain unclear. METHODS: Wild-type (WT) and CRTH2-knockout (KO) mice were sensitized with ovalbumin (OVA) without an adjuvant and then challenged intranasally with OVA. Airway inflammation was assessed based on airway hyperresponsiveness (AHR), lung histology, number of leukocytes, and levels of type-2 cytokines in the bronchoalveolar lavage fluid (BALF). RESULTS: AHR was significantly reduced after OVA challenge in CRTH2 KO mice compared to WT mice. The number of eosinophils, levels of type-2 cytokines (IL-4, IL-5, and IL-13) in BALF, and IgE concentration in serum were decreased in CRTH2 KO mice compared to WT mice. However, lung histological changes were comparable between WT and CRTH2 KO mice. CONCLUSION: CRTH2 is responsible for the development of asthma responses in a mouse model of airway inflammation that features prominent involvement of both IgE and mast cells.

IL-17A-Secreting Memory γδ T Cells Play a Pivotal Role in Sensitization and Development of Hypersensitivity Pneumonitis.

Hypersensitivity pneumonitis (HP) typically presents with interstitial inflammation and granulomas induced by an aberrant immune response to inhaled Ags in sensitized individuals. Although IL-17A is involved in the development of HP, the cellular sources of IL-17A and the mechanisms by which IL-17A contributes to granuloma formation remain unclear. Recent studies report that γδ T cells produce IL-17A and exhibit memory properties in various diseases. Therefore, we focused on IL-17A-secreting memory γδ T cells in the sensitization phase and aimed to elucidate the mechanisms by which IL-17A contributes to granuloma formation in HP. We induced a mouse model of HP using pigeon dropping extract (PDE) in wild-type and IL-17A knockout (IL-17A-/-) mice. IL-17A-/- mice exhibited reduced granulomatous areas, attenuated aggregation of CD11b+ alveolar macrophages, and reduced levels of CCL2, CCL4, and CCL5 in the bronchoalveolar lavage fluid. Among IL-17A+ cells, more γδ T cells than CD4+ cells were detected after intranasal PDE administration. Interestingly, the expansion of IL-17A-secreting Vγ4+ or Vγ1-Vγ4- cells of convalescent mice was enhanced in response to the sensitizing Ag. Additionally, coculture of macrophages with PDE and Vγ4+ cells purified from PDE-exposed convalescent mice produced significantly more IL-17A than coculture with Vγ4+ cells from naive mice. Our findings demonstrate that in the sensitization phase of HP, IL-17A-secreting memory γδ T cells play a pivotal role. Furthermore, we characterized the IL-17A/CCL2, CCL4, CCL5/CD11b+ alveolar macrophage axis, which underlies granuloma formation in HP. These findings may lead to new clinical examinations or therapeutic targets for HP.

Understanding the process of people with hypersensitivity pneumonitis implementing continuous antigen avoidance and their affecting situations: A grounded theory study.

AIMS AND OBJECTIVES: To explore the process by which people with hypersensitivity pneumonitis implement continuous antigen avoidance, alongside the situations that influence this process. BACKGROUND: Antigen avoidance is the primary treatment for people with hypersensitivity pneumonitis. However, the best method to support antigen avoidance has not yet been established. DESIGN: The present qualitative study used a constructivist grounded theory approach. METHODS: The participants were inpatients or outpatients with hypersensitivity pneumonitis diagnosed at a Japanese urban university hospital. In parallel with semi-structured interviews and a medical record survey from 2016 to 2021, we conducted coding, categorising, writing memos, theoretical sampling and continuous comparisons of experiences from finding physical abnormalities to implementing antigen avoidance. The COREQ checklist was followed for reporting. RESULTS: Interpreting the experiences leading to the implementation of continuous antigen avoidance by 28 participants provided a process consisting of a core category: trying to maintain one's desired life under uncertain situations, and four phases: (1) searching for a convincing cause of the illness, (2) gradually understanding the disease, (3) realising the need for behaviour change and (4) seeking a good balance between behaviour change and one's desired life. The situations that influenced the process were also revealed. CONCLUSIONS: Being convinced of the cause of one's illness and realising its severity led to the participants' realisation of the need for a behavioural change to avoid antigens. The uncertainty of the cause of illness and measures taken, a lack of clear advice from healthcare providers and one's desired life influenced participants' implementation of continuous antigen avoidance. RELEVANCE TO CLINICAL PRACTICE: This study provides important insights regarding how healthcare providers should better understand and support people with hypersensitivity pneumonitis in avoiding antigens.

Mass-like Lesions Causing Compression of Large Vessels in Granulomatosis with Polyangiitis.

A 69-year-old woman with a history of otitis media with anti-neutrophil cytoplasmic antibody-associated vasculitis who had been receiving corticosteroid monotherapy presented with shortness of breath. The otitis media had been alleviated, but she had saddle nose. Chest enhanced computed tomography showed stenoses of the bronchi and large vessels surrounded by mass-like lesions in the mediastinum. These manifestations indicated an active state of granulomatosis with polyangiitis (GPA). After she was started on high-dose corticosteroids and intravenous cyclophosphamide, the mass-like lesions disappeared with improvements of the stenoses. Ameliorating mass-like lesions resulting from GPA requires therapeutic intervention using corticosteroids and immunosuppressants.

Construction of affinity changeable antibody in response to Ca2+.

Immunoaffinity chromatography is a powerful method for purification of proteins because of the high selectivity and avidity of antibodies. Due to the strength of antigen-antibody binding, however, elution of proteins bound to antibodies that are covalently immobilized on the column is performed by temporary denaturation of the antibody. Therefore, the development of milder elution conditions could improve the recovery of the antibodies and prolong the life of the immunoaffinity column. We describe the design and construction of an antibody that changes its affinity in response to external stimuli. The heavy chain and light chain of a single chain Fv of the D1.3 antibody against hen egg-white lysozyme (HEL) were fused at the N- and C-termini, respectively, of the calmodulin-M13 fusion protein. The affinity of this fusion protein for HEL could be modulated by changing the Ca(2+) concentration.

Pleurisy with pneumothorax due to CAM-resistant MAC lung disease.

A 72-year-old man received rifampicin, ethambutol and sitafloxacin to treat clarithromycin (CAM)-resistant Mycobacterium avium complex (MAC) lung disease. He was admitted because of fever. Pneumothorax and pleural effusion were present in the right lung, and a new consolidation appeared in the right upper lobe. Based on positive culture of the pleural effusion for CAM-resistant M. avium and findings on chest computed tomography, he was diagnosed with pleurisy due to M. avium, with rupture of the subpleural lung parenchymal lesion into the pleural space. Additional treatment with streptomycin (SM) improved the patient's high-grade fever. SM might be effective for pleurisy caused by CAM-resistant MAC lung disease.

Changes in serum KL-6 levels during short-term strict antigen avoidance are associated with the prognosis of patients with fibrotic hypersensitivity pneumonitis caused by avian antigens.

BACKGROUND: Bird-related hypersensitivity pneumonitis (BRHP) is the most common type of fibrotic hypersensitivity pneumonitis (HP). Antigen avoidance (AA) is a key step in the diagnosis and management of HP, but not all fibrotic HP patients improve through AA. Because of the poor prognosis of fibrotic HP, predictive biomarkers to identify patients showing rapid progression during AA are urgently needed. METHODS: From a retrospective review of the medical records of 1941 patients with interstitial lung disease, 75 cases of fibrotic BRHP confirmed by a provocation test or surgical lung biopsy were identified. To identify potential prognostic markers obtained at or around diagnosis, physiological and serological variables at diagnosis and the relative changes in those variables during strict AA were evaluated. Cox proportional hazards models with log-rank testing were used to compare the associations between these variables and survival. RESULTS: Univariate analyses showed that gender, smoking status, and the relative change in the serum levels of Krebs von den Lungen-6 (KL-6) were associated with prognosis (P = 0.02, 0.04, and 0.02, respectively), but the presence of honeycombing and the forced vital capacity were not associated with survival. The relative change in KL-6 levels (greater than vs. less than a 10% decrease) was significantly associated with survival in a stratified analysis (73.9 vs. 34.9 months; P = 0.04). CONCLUSIONS: The relative change in KL-6 levels is associated with the prognosis of patients with fibrotic BRHP independent of previously identified prognostic biomarkers. This finding could help pulmonologists identify fibrotic BRHP patients that are likely to show rapid progression.

The Analysis of Surgical Lung Biopsy and Explanted Lung Specimens Sheds Light on the Pathological Progression of Chronic Bird-related Hypersensitivity Pneumonitis.

Chronic hypersensitivity pneumonitis is an interstitial pneumonia caused by an immunological reaction to the chronic inhalation of an antigen. Little is known, however, about the pathological change of the pulmonary lesions. A 33-year-old man was diagnosed with chronic bird-related hypersensitivity pneumonitis based on the findings of a surgical lung biopsy and an inhalation provocation test. He underwent lung transplantation at 8 years after the diagnosis because of disease progression. We conclude that the analysis of the explant suggests that the presence of extensive fibrosis in the centrilobular and perilobular area with bridging fibrosis is a form of pathological progression of chronic hypersensitivity pneumonitis.

[Gastric functions using capsules containing contrast medium: characteristics in patients with esophagitis].

We studied gastric function in patients with functional dyspepsia, using capsules containing contrast medium. We were able to estimate intragastric capsule movement by this method. Here, we report gastric functions in patients with esophagitis. We were able to recognize gastric dysfunction (delayed gastric emptying) in these patients.