RESUMEN
BACKGROUND: Two opposing B cell subsets have been defined based on their cytokine profile: IL-6 producing effector B cells (B-effs) versus IL-10 producing regulatory B cells (B-regs) that respectively positively or negatively regulate immune responses. B-regs are decreased and/or impaired in many autoimmune diseases and inflammatory conditions. Since there is increasing evidence that links B cells and B cell-rich lymphoid follicles to the pathogenesis of COPD, the aim of this study was to investigate the presence and function of B-regs in COPD. METHODS: First, presence of IL-10 producing regulatory B cells in human lung tissue was determined by immunohistochemistry. Secondly, quantification of IL-10 + B-regs and IL-6 + B-effs in peripheral blood mononuclear cells (PBMCs) from healthy controls, smokers without airflow limitation, and COPD patients (GOLD stage I-IV) was performed by flow cytometry. Thirdly, we exposed blood-derived B cells from COPD patients in vitro to cigarette smoke extract (CSE) and quantified IL-10 + B-regs and IL-6 + B-effs. Furthermore, we aimed at restoring the perturbed IL10 production by blocking BAFF. Fourthly, we determined mRNA expression of transcription factors involved in IL-10 production in FACS sorted memory- and naive B cells upon exposure to medium or CSE. RESULTS: The presence of IL-10 producing regulatory B cells in parenchyma and lymphoid follicles in lungs was confirmed by immunohistochemistry. The percentage of IL-10 + B-regs was significantly decreased in blood-derived memory B cell subsets from smokers without airflow limitation and patients with COPD, compared to never smokers. Furthermore, the capacity of B cells to produce IL-10 was reduced upon in vitro exposure to CSE and this could not be restored by BAFF-blockade. Finally, upon CSE exposure, mRNA levels of the transcription factors IRF4 and HIF-1α, were decreased in memory B cells. CONCLUSION: Decreased numbers and impaired function of B-regs in smokers and patients with COPD might contribute to the initiation and progression of the disease.
Asunto(s)
Linfocitos B Reguladores , Enfermedad Pulmonar Obstructiva Crónica , Linfocitos B Reguladores/metabolismo , Humanos , Interleucina-10 , Interleucina-6/metabolismo , Enfermedad Pulmonar Obstructiva Crónica/metabolismo , ARN Mensajero , Fumadores , Nicotiana , Factores de TranscripciónRESUMEN
Background: Long-term outcome data of coronavirus disease 2019 (COVID-19) survivors are needed to understand their recovery trajectory and additional care needs. Methods: A prospective observational multicentre cohort study was carried out of adults hospitalised with COVID-19 from March through May 2020. Workup at 3 and 12â months following admission consisted of clinical review, pulmonary function testing, 6-min walk distance (6MWD), muscle strength, chest computed tomography (CT) and quality of life questionnaires. We evaluated factors correlating with recovery by linear mixed effects modelling. Results: Of 695 patients admitted, 299 and 226 returned at 3 and 12â months, respectively (median age 59â years, 69% male, 31% severe disease). About half and a third of the patients reported fatigue, dyspnoea and/or cognitive impairment at 3 and 12â months, respectively. Reduced 6MWD and quadriceps strength were present in 20% and 60% at 3â months versus 7% and 30% at 12â months. A high anxiety score and body mass index correlated with poor functional recovery. At 3â months, diffusing capacity for carbon monoxide (D LCO) and total lung capacity were below the lower limit of normal in 35% and 18%, decreasing to 21% and 16% at 12â months; predictors of poor D LCO recovery were female sex, pre-existing lung disease, smoking and disease severity. Chest CT improved over time; 10% presented non-progressive fibrotic changes at 1â year. Conclusion: Many COVID-19 survivors, especially those with severe disease, experienced limitations at 3â months. At 1â year, the majority showed improvement to almost complete recovery. To identify additional care or rehabilitation needs, we recommend a timely multidisciplinary follow-up visit following COVID-19 admission.