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Machine learning–based deep phenotyping of atopic dermatitis: severity-associated factors in adolescent and adult patients ()
Atopic dermatitis: factors associated with age of onset in adulthood versus childhood [Abstract] ()
Atopic dermatitis: correlation of distinct risk factors with age of onset in adulthood compared to childhood ()
Spatial transcriptomics combined with single‐cell RNA‐sequencing unravels the complex inflammatory cell network in atopic dermatitis ()
Background Atopic dermatitis (AD) is the most common chronic inflammatory skin disease with complex pathogenesis for which the cellular and molecular crosstalk in AD skin has not been fully understood. Methods Skin tissues examined for spatial gene expression were derived from the upper arm of 6 healthy control (HC) donors and 7 AD patients (lesion and nonlesion). We performed spatial transcriptomics sequencing to characterize the cellular infiltrate in lesional skin. For single-cell analysis, we analyzed the single-cell data from suction blister material from AD lesions and HC skin at the antecubital fossa skin (4 ADs and 5 HCs) and full-thickness skin biopsies (4 ADs and 2 HCs). The multiple proximity extension assays were performed in the serum samples from 36 AD patients and 28 HCs. Results The single-cell analysis identified unique clusters of fibroblasts, dendritic cells, and macrophages in the lesional AD skin. Spatial transcriptomics analysis showed the upregulation of COL6A5, COL4A1, TNC, and CCL19 in COL18A1-expressing fibroblasts in the leukocyte-infiltrated areas in AD skin. CCR7-expressing dendritic cells (DCs) showed a similar distribution in the lesions. Additionally, M2 macrophages expressed CCL13 and CCL18 in this area. Ligand–receptor interaction analysis of the spatial transcriptome identified neighboring infiltration and interaction between activated COL18A1-expressing fibroblasts, CCL13- and CCL18-expressing M2 macrophages, CCR7- and LAMP3-expressing DCs, and T cells. As observed in skin lesions, serum levels of TNC and CCL18 were significantly elevated in AD, and correlated with clinical disease severity. Conclusion In this study, we show the unknown cellular crosstalk in leukocyte-infiltrated area in lesional skin. Our findings provide a comprehensive in-depth knowledge of the nature of AD skin lesions to guide the development of better treatments.
Advances and highlights in biomarkers of allergic diseases ()
During the past years, there has been a global outbreak of allergic diseases, presenting a considerable medical and socioeconomical burden. A large fraction of allergic diseases is characterized by a type 2 immune response involving Th2 cells, type 2 innate lymphoid cells, eosinophils, mast cells, and M2 macrophages. Biomarkers are valuable parameters for precision medicine as they provide information on the disease endotypes, clusters, precision diagnoses, identification of therapeutic targets, and monitoring of treatment efficacies. The availability of powerful omics technologies, together with integrated data analysis and network-based approaches can help the identification of clinically useful biomarkers. These biomarkers need to be accurately quantified using robust and reproducible methods, such as reliable and point-of-care systems. Ideally, samples should be collected using quick, cost-efficient and noninvasive methods. In recent years, a plethora of research has been directed toward finding novel biomarkers of allergic diseases. Promising biomarkers of type 2 allergic diseases include sputum eosinophils, serum periostin and exhaled nitric oxide. Several other biomarkers, such as pro-inflammatory mediators, miRNAs, eicosanoid molecules, epithelial barrier integrity, and microbiota changes are useful for diagnosis and monitoring of allergic diseases and can be quantified in serum, body fluids and exhaled air. Herein, we review recent studies on biomarkers for the diagnosis and treatment of asthma, chronic urticaria, atopic dermatitis, allergic rhinitis, chronic rhinosinusitis, food allergies, anaphylaxis, drug hypersensitivity and allergen immunotherapy. In addition, we discuss COVID-19 and allergic diseases within the perspective of biomarkers and recommendations on the management of allergic and asthmatic patients during the COVID-19 pandemic.
Deciphering the connection between atopic dermatitis and cardiovascular diseases: analysis of clinical associations and cardiometabolic proteins ()
Aerosol measurements and decadal changes: the role of climatic changes and how it reflects in respiratory allergies and asthma ()
The causative agents of respiratory allergies are bioaerosols, such as house dust mite feces, pollen grains, and fungal spores. Climate change and urbanization are considered to lead to an increase in the load of allergenic bioaerosols due to impacts on plant phenophases and allergenicity. Continuous and efficient monitoring of the atmospheric composition worldwide is essential, given the major changes involved and their impact on climate change. The complexity of the exposome, evolving from single to multiple complex exposures, is explored in this work. Acquiring information from interdisciplinary scientific disciplines, such as aerobiology (for airborne particles of biological origin), aerosol science (for airborne particles of chemical or inorganic material), and integrating this with the actual reactome of patients with respiratory diseases, we aim to provide evidence of the multifactorial nature of this interaction in real life. The objective of this review is to present how we can monitor aerosols and mostly monitor the exposome, especially the biological one, i.e., pollen and fungal spores, and what their impact is, or could be, on respiratory allergies. A huge technological advancement has been required, as traditional methods of particle collection and identification have been based on tedious laboratory procedures, with delays of more than a week. This has limited their practical use to allergic patients and their treating physicians. Automation, real-time high temporal resolution, and the use of artificial intelligence are being increasingly used in medicine. Likewise, this overview summarizes the current aerosol measurement and modeling capabilities and discusses the classification of various aerosol particles and their impact on respiratory allergies. Satellite remote sensing is highlighted as a solution to the gaps in global aerosol representation by examining aerosol load in the atmospheric column in major cities worldwide. We also discuss potential novel threats, such as pioneer bioaerosols and the respiratory epithelial barrier, as well as future insights into the impact of climate change on allergy and asthma. We conclude with a discussion of emerging co-exposures and co-diseases resulting from the ongoing climate change.
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