Fractional exhaled nitric oxide, a potential biomarker for evaluating glucocorticoids treatment and prognosis in allergic bronchopulmonary aspergillosis.

BACKGROUND: Allergic bronchopulmonary aspergillosis (ABPA) is characterized by enhanced TH2 inflammatory response. Fractional exhaled nitric oxide (FeNO) measurement has been used as a valuable tool in predicting the development and management of asthma, another typical TH2 inflammation. However, the clinical significance of FeNO in ABPA remains unclear. OBJECTIVE: To investigate the association between FeNO and the prognosis of patients with ABPA to provide a basis for the use of FeNO in evaluating the efficacy of glucocorticoids in ABPA treatment. METHODS: This study comprised 2 parts; 58 patients were enrolled in the retrospective study. Clinical indexes in patients with different prognoses were compared, and receiver operating characteristic curve analysis was used to determine the threshold value. The prospective observational study involved 61 patients who were regularly followed up at 4 to 6 weeks and 6 months since the initial treatment. Patients were grouped on the basis of baseline FeNO values; correlation analysis was performed in the clinical data. RESULTS: Different prognoses were observed between patients with high and low baseline FeNO values, with a threshold value of 57 parts per billion. The percentage of Aspergillus fumigatus-specific IgE, percentage of positive A fumigatus-specific IgG, and relapse/exacerbation rate differed significantly between the high and low FeNO groups. Patients with higher FeNO needed longer treatment duration and showed shorter interval between glucocorticoid withdrawal and the next relapse/exacerbation. CONCLUSION: Our findings indicate that the level of FeNO is associated with the prognosis of ABPA. It can serve as an independent and valuable biomarker for evaluating the effectiveness of glucocorticoid treatment.

Th2-skewed peripheral T-helper cells drive B-cells in allergic bronchopulmonary aspergillosis.

INTRODUCTION: Patients with allergic bronchopulmonary aspergillosis (ABPA) suffer from repeated exacerbations. The involvement of T-cell subsets remains unclear. METHODS: We enrolled ABPA patients, asthma patients and healthy controls. T-helper type 1 (Th1), 2 (Th2) and 17 (Th17) cells, regulatory T-cells (Treg) and interleukin (IL)-21+CD4+T-cells in total or sorted subsets of peripheral blood mononuclear cells and ABPA bronchoalveolar lavage fluid (BALF) were analysed using flow cytometry. RNA sequencing of subsets of CD4+T-cells was done in exacerbated ABPA patients and healthy controls. Antibodies of T-/B-cell co-cultures in vitro were measured. RESULTS: ABPA patients had increased Th2 cells, similar numbers of Treg cells and decreased circulating Th1 and Th17 cells. IL-5+IL-13+IL-21+CD4+T-cells were rarely detected in healthy controls, but significantly elevated in the blood of ABPA patients, especially the exacerbated ones. We found that IL-5+IL-13+IL-21+CD4+T-cells were mainly peripheral T-helper (Tph) cells (PD-1+CXCR5-), which also presented in the BALF of ABPA patients. The proportions of circulating Tph cells were similar among ABPA patients, asthma patients and healthy controls, while IL-5+IL-13+IL-21+ Tph cells significantly increased in ABPA patients. Transcriptome data showed that Tph cells of ABPA patients were Th2-skewed and exhibited signatures of follicular T-helper cells. When co-cultured in vitro, Tph cells of ABPA patients induced the differentiation of autologous B-cells into plasmablasts and significantly enhanced the production of IgE. CONCLUSION: We identified a distinctly elevated population of circulating Th2-skewed Tph cells that induced the production of IgE in ABPA patients. It may be a biomarker and therapeutic target for ABPA.

Root endophyte-mediated alteration in plant H2O2 homeostasis regulates symbiosis outcome and reshapes the rhizosphere microbiota.

Endophytic symbioses between plants and fungi are a dominant feature of many terrestrial ecosystems, yet little is known about the signaling that defines these symbiotic associations. Hydrogen peroxide (H2O2) is recognized as a key signal mediating the plant adaptive response to both biotic and abiotic stresses. However, the role of H2O2 in plant-fungal symbiosis remains elusive. Using a combination of physiological analysis, plant and fungal deletion mutants, and comparative transcriptomics, we reported that various environmental conditions differentially affect the interaction between Arabidopsis and the root endophyte Phomopsis liquidambaris, and link this process to alterations in H2O2 levels and H2O2 fluxes across root tips. We found that enhanced H2O2 efflux leading to a moderate increase in H2O2 levels at the plant-fungal interface is required for maintaining plant-fungal symbiosis. Disturbance of plant H2O2 homeostasis compromises the symbiotic ability of plant roots. Moreover, the fungus-regulated H2O2 dynamics modulate the rhizosphere microbiome by selectively enriching for the phylum Cyanobacteria, with strong antioxidant defenses. Our results demonstrated that the regulation of H2O2 dynamics at the plant-fungal interface affects the symbiotic outcome in response to external conditions and highlight the importance of the root endophyte in reshaping the rhizosphere microbiota.