Background Chronic Obstructive Pulmonary Disease (COPD) is a common inflammatory disease of the airways characterized by irreversible airflow limitation, ranking the third highest cause of death worldwide. Extracellular vesicles (EVs) are important intercellular communication mediators released by cells into their extracellular environment with the capacity to transfer biological signals. EVs involved in COPD hold great potential to understand disease pathogenesis and identify important biomarkers. This systematic review aims to examine all available research on EVs in the pathogenesis and diagnosis of COPD to identify existing knowledge and support further research within the field. Methods Publications were searched using PubMed and EMBASE with the search terms (Exosomes or extracellular vesicles or microvesicles or microparticles or ectosomes) AND (chronic obstructive pulmonary disease or COPD or emphysema or bronchitis). Results Initial search yielded 512 papers of which 142 were manually selected for review and 43 were eligible for analyses. The studies were divided into groups according to the role of EVs in pathogenesis, EV origin and cargo, their role in COPD exacerbations and their diagnostic utility. EVs were found to be involved in the mechanism of pathogenesis of COPD, derived from various cell types, as well as containing modified levels of miRNAs. EVs also varied according to the pathophysiological status of disease, therefore presenting a possible method for COPD diagnosis and progress monitoring. Conclusion The current findings show the limited but good quality research looking at the role of EVs in COPD, demonstrating the need for more studies to better define and provide further insight into the functional characteristics of EV in COPD pathogenesis.

Objectives COVID-19 vaccine responses in rare autoimmune rheumatic diseases (RAIRD) remain poorly understood, in particular there is little known about whether people develop effective T cell responses. We conducted an observational study to evaluate the short-term humoral and cell-mediated T cell response after the second SARS-CoV-2 vaccination in RAIRD patients compared with healthy controls (HC). Methods Blood samples were collected after the second dose and anti-spike, anti-nucleocapsid antibody levels and SARS-CoV-2 specific T cell responses were measured and compared with HC. Activation induced marker and deep phenotyping assays were used to identify differences in T cells between high and low/no antibody groups, followed by multi-dimensional clustering. Results 50 patients with RAIRD were included (31 with AAV, 4 with other systemic vasculitis, 9 with SLE and 6 with myositis). Median anti-spike levels were significantly lower in RAIRD compared with HC (p< 0.0001). 15 (33%) patients had undetectable and 26 (57%) had lower levels than the lowest HC. Rituximab in the last 12 months (p= 0.003) was associated with reduced immunogenicity compared with a longer pre-vaccination period. There was a significant difference in B cell percentages (p= 0.03) and spike-specific CD4+ T cells (p= 0.02) between no/low antibody vs. high antibody groups. Patients in the no/low antibody group had a higher percentage of terminally differentiated (exhausted) T cells. Conclusions Following two doses, most RAIRD patients have lower antibody levels than the lowest HC and lower anti-spike T cells. RAIRD patients with low/no antibodies have diminished numbers and poor quality of memory T cells which lack proliferative and functional capacities.

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Extracellular vesicles (EVs) function as mediators of intercellular communication and as such influence the recipient cell function. EVs derived from immune cells can carry out many of the same functions as their parental cells, as they carry costimulatory molecules, antigens, and antigen–MHC complexes. As a result, there is a strong interest in understanding the composition and origin of immune cell–derived EVs in order to understand their role in the pathogenesis of diseases. This study aimed to optimize methodologies to study immune cell–derived EVs. Peripheral blood mononuclear cell‐derived small EVs were isolated and observed using conventional transmission electron microscopy and sized by nanoparticle tracking analysis. They were then enumerated and profiled using imaging flow cytometry and were further characterized using a flow cytometric multiplex bead assay. These techniques were then applied to our current research, namely smoking‐related inflammatory disease. We present here a comprehensive approach to analyze PBMC‐derived small EVs in smoking‐related inflammatory disease following the Minimal Information for Studies of Extracellular Vesicle 2018 guidelines.

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