Adeno-associated virus type 5 infection via PDGFRα is associated with Interstitial lung disease in systemic sclerosis and generates composite peptides and epitopes recognized by the agonistic immunoglobulins present in patients with systemic sclerosis

Objectives: The etiopathogenesis of systemic sclerosis (SSc) is unknown. Platelet-derived growth factor receptors (PDGFRs) are overexpressed in SSc patients. Since PDGFRα is targeted of the adeno-associated virus type 5 (AAV5), we investigated whether AAV5 forms a complex with PDGFRα exposing epitopes that may induce the immune responses to the virus-PDGFRα complex. Methods: The binding of monomeric human PDGFRα to the AAV5 capsid was analyzed by in silico molecular docking, surface plasmon resonance (SPR), and genome editing of the PDGFRα locus. AAV5 was detected in SSc lungs by in situ hybridization, immunohistochemistry, confocal microscopy, and molecular analysis of bronchoalveolar lavage (BAL). Immune responses to AAV5 and PDGFRα were evaluated by SPR using SSc monoclonal anti-PDGFRα antibodies and Immunoaffinity-purified anti-PDGFRα antibodies from sera of SSc patients. Results: AAV5 was detected in the BAL of 41 out of 66 (62.1%) SSc patients with interstitial lung disease and in 17 of 66 controls (25.75 %; p<0.001). In SSc lungs, AAV5 localized in type II pneumocytes and in interstitial cells. A molecular complex formed of spatially contiguous epitopes of the AAV5 capsid and PDGFRα was identified and characterized. In silico molecular docking analysis and binding to the agonistic anti-PDGFRα antibodies identified spatially contiguous epitopes derived from PDGFRα and AAV5 that interacted with SSc agonistic antibodies to PDGFRα. These peptides were also able to bind total IgG isolated from SSc patients, not from healthy controls. Conclusions: These data link AVV5 with the immune reactivity to endogenous antigens in SSc, and provide a novel element in the pathogenesis of SSc

Toward the integrated marine debris observing system

Plastics and other artificial materials pose new risks to the health of the ocean. Anthropogenic debris travels across large distances and is ubiquitous in the water and on shorelines, yet, observations of its sources, composition, pathways, and distributions in the ocean are very sparse and inaccurate. Total amounts of plastics and other man-made debris in the ocean and on the shore, temporal trends in these amounts under exponentially increasing production, as well as degradation processes, vertical fluxes, and time scales are largely unknown. Present ocean circulation models are not able to accurately simulate drift of debris because of its complex hydrodynamics. In this paper we discuss the structure of the future integrated marine debris observing system (IMDOS) that is required to provide long-term monitoring of the state of this anthropogenic pollution and support operational activities to mitigate impacts on the ecosystem and on the safety of maritime activity. The proposed observing system integrates remote sensing and in situ observations. Also, models are used to optimize the design of the system and, in turn, they will be gradually improved using the products of the system. Remote sensing technologies will provide spatially coherent coverage and consistent surveying time series at local to global scale. Optical sensors, including high-resolution imaging, multi- and hyperspectral, fluorescence, and Raman technologies, as well as SAR will be used to measure different types of debris. They will be implemented in a variety of platforms, from hand-held tools to ship-, buoy-, aircraft-, and satellite-based sensors. A network of in situ observations, including reports from volunteers, citizen scientists and ships of opportunity, will be developed to provide data for calibration/validation of remote sensors and to monitor the spread of plastic pollution and other marine debris. IMDOS will interact with other observing systems monitoring physical, chemical, and biological processes in the ocean and on shorelines as well as the state of the ecosystem, maritime activities and safety, drift of sea ice, etc. The synthesized data will support innovative multi-disciplinary research and serve a diverse community of users

EMODnet marine litter data management at pan-European scale

Marine litter is a growing problem for environmental and human health and policies have included monitoring as an important tool to evaluate both trends and the efficiency of reduction measures. The Marine Strategy Framework Directive is the main driver in Europe for the monitoring of the marine environment; it has included the evaluation of marine litter in order to support policies and achieve good environmental status. This assessment depends on the availability of robust, homogeneous data-sets at the European scale. A data management plan for marine litter has been developed at European level within the existing EMODnet network to collect, homogenise and provide access to standardised data-sets and data products that may be used as a basis for marine litter assessment at pan-European scale. As a long term perspective, it also provides a scientific and technical basis for further global monitoring

CD8+ T-cell alveolitis in familial pulmonary alveolar microlithiasis

Pulmonary alveolar microlithiasis (PAM) is a rare diffuse lung disease characterised by the accumulation of calcium phosphate microliths within the alveoli. The causative mechanism of PAM has only recently been discovered, and involves a gene mutation of sodium phosphate co-transporter, which is expressed by alveolar epithelial cells. This mutation may have variable consequences on the clinical phenotype. However, pulmonary cell immune phenotyping in familial PAM has not previously been assessed. In the present article, the analysis of bronchoalveolar lavage fluid of two siblings with PAM diagnosis revealed a pattern of lymphocytic alveolitis with accumulation of CD8+ T-cells. The clonal complexity of this lymphocyte's population was assayed by spectratyping, which showed an oligoclonal accumulation of T-cells with a restricted variable beta T-cell receptor (TCR) gene usage. TCR analysis in peripheral blood lymphocytes revealed no abnormal patterns of T-lymphocytes. In the pulmonary alveolar microlithiasis familial cases reported, CD8-mediated maladaptive immune response may have taken place in the bronchoalveolar compartment. The relationship between this immune dysregulation and genetic background in pulmonary alveolar microlithiasis warrants further investigation