Allergies, including asthma, food allergy and atopic dermatitis, are increasing in prevalence, particularly in westernized countries. Although a detailed mechanistic explanation for this increase is ...lacking, recent evidence indicates that, in addition to genetic predisposition, lifestyle changes owing to modernization have an important role. Such changes include increased rates of birth by caesarean delivery, increased early use of antibiotics, a westernized diet and the associated development of obesity, and changes in indoor and outdoor lifestyle and activity patterns. Most of these factors directly and indirectly impact the formation of a diverse microbiota, which includes bacterial, viral and fungal components; the microbiota has a leading role in shaping (early) immune responses. This default programme is markedly disturbed under the influence of environmental and lifestyle risk factors. Here, we review the most important allergy risk factors associated with changes in our exposure to the microbial world and the application of this knowledge to allergy prevention strategies.
Asthma-associated risk for COVID-19 development Skevaki, Chrysanthi; Karsonova, Antonina; Karaulov, Alexander ...
Journal of allergy and clinical immunology,
12/2020, Letnik:
146, Številka:
6
Journal Article
Recenzirano
Odprti dostop
The newly described severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for a pandemic (coronavirus disease 2019 COVID-19). It is now well established that certain ...comorbidities define high-risk patients. They include hypertension, diabetes, and coronary artery disease. In contrast, the context with bronchial asthma is controversial and shows marked regional differences. Because asthma is the most prevalent chronic inflammatory lung disease worldwide and SARS-CoV-2 primarily affects the upper and lower airways leading to marked inflammation, the question arises about the possible clinical and pathophysiological association between asthma and SARS-CoV-2/COVID-19. Here, we analyze the global epidemiology of asthma among patients with COVID-19 and propose the concept that patients suffering from different asthma endotypes (type 2 asthma vs non–type 2 asthma) present with a different risk profile in terms of SARS-CoV-2 infection, development of COVID-19, and progression to severe COVID-19 outcomes. This concept may have important implications for future COVID-19 diagnostics and immune-based therapy developments.
The mucosal surfaces of the gut and airways have important barrier functions and regulate the induction of immunological tolerance. The rapidly increasing incidence of chronic inflammatory disorders ...of these surfaces, such as inflammatory bowel disease and asthma, indicates that the immune functions of these mucosae are becoming disrupted in humans. Recent data indicate that events in prenatal and neonatal life orchestrate mucosal homeostasis. Several environmental factors promote the perinatal programming of the immune system, including colonization of the gut and airways by commensal microorganisms. These complex microbial-host interactions operate in a delicate temporal and spatial manner and have an important role in the induction of homeostatic mechanisms.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
COVID-19 is associated with a wide range of clinical manifestations, including autoimmune features and autoantibody production. Here we develop three protein arrays to measure IgG autoantibodies ...associated with connective tissue diseases, anti-cytokine antibodies, and anti-viral antibody responses in serum from 147 hospitalized COVID-19 patients. Autoantibodies are identified in approximately 50% of patients but in less than 15% of healthy controls. When present, autoantibodies largely target autoantigens associated with rare disorders such as myositis, systemic sclerosis and overlap syndromes. A subset of autoantibodies targeting traditional autoantigens or cytokines develop de novo following SARS-CoV-2 infection. Autoantibodies track with longitudinal development of IgG antibodies recognizing SARS-CoV-2 structural proteins and a subset of non-structural proteins, but not proteins from influenza, seasonal coronaviruses or other pathogenic viruses. We conclude that SARS-CoV-2 causes development of new-onset IgG autoantibodies in a significant proportion of hospitalized COVID-19 patients and are positively correlated with immune responses to SARS-CoV-2 proteins.
Growing up on a farm is associated with an asthma-protective effect, but the mechanisms underlying this effect are largely unknown. In the Protection against Allergy: Study in Rural Environments ...(PASTURE) birth cohort, we modeled maturation using 16S rRNA sequence data of the human gut microbiome in infants from 2 to 12 months of age. The estimated microbiome age (EMA) in 12-month-old infants was associated with previous farm exposure (β = 0.27 (0.12-0.43), P = 0.001, n = 618) and reduced risk of asthma at school age (odds ratio (OR) = 0.72 (0.56-0.93), P = 0.011). EMA mediated the protective farm effect by 19%. In a nested case-control sample (n = 138), we found inverse associations of asthma with the measured level of fecal butyrate (OR = 0.28 (0.09-0.91), P = 0.034), bacterial taxa that predict butyrate production (OR = 0.38 (0.17-0.84), P = 0.017) and the relative abundance of the gene encoding butyryl-coenzyme A (CoA):acetate-CoA-transferase, a major enzyme in butyrate metabolism (OR = 0.43 (0.19-0.97), P = 0.042). The gut microbiome may contribute to asthma protection through metabolites, supporting the concept of a gut-lung axis in humans.
GATA3 is thought to be a critical checkpoint in allergic diathesis. In this study, a synthetic DNAzyme that catalyzes the inactivation of GATA3 when administered by inhalation attenuated the late ...asthmatic response in laboratory challenges.
Asthma is a common chronic inflammatory disease of the airways that is characterized by variable airway obstruction, hypersecretion of mucus, airway inflammation, and hyperresponsiveness of the airways. The dysregulation of innate and adaptive immune responses is considered to play a central role in the development of the disease. The high degree of interindividual heterogeneity identified in different patient populations has led to the definition of several clinical phenotypes and pathophysiological endotypes.
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The allergic response driven by the type 2 helper T cell (Th2),
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,
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also termed the Th2 molecular endotype, is thought to be characteristic of allergic asthma.
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Importantly, if they activate autophagy in eosinophils, this counterregulates eosinophil cytolysis....the authors not only demonstrate in a very elegant fashion a new pathway for eosinophil ...cytolysis, they were also able to link cytolysis with counterregulating autophagy and open new pathways for at least experimental intervention.Interestingly, autophagy, rather than endoplasmic reticulum stress, contributed to IL-13-induced eotaxin-3 peptide secretion also from human airway epithelial cells.6-8 A link between the epithelial-mesenchymal transition unit and autophagy has been shown in other models of allergic asthma.9,10 A further link between autophagy and asthma has been established for human rhinovirus, respiratory syncytial virus, coronavirus, adenovirus, and influenza A virus through the role of autophagy in the defense against respiratory tract viruses, which represent a major exacerbation factor for asthma.Table I Key discoveries on the journey to the autophagosome 1955 Lysosomes de Duve 1966 Function of lysosome (“autophagy”) de Duve 1968 Autophagosome Arstila, Trump 1979 Proteasome Harshko, Chiecanova, Rose 1980 Ubiquitin Wilkinson, Urban, Haas 1992 Autophagosome as machinery of autophagy Ohsumi 1993 The first autophagy gene, ATG1 Ohsumi 1 M. Tsukada, Y. Ohsumi, Saccharomyces cerevisiae, FEBS Lett, Vol. 333, 1993, 169-174 2 K. Takeshige, M. Baba, S. Tsuboi, T. Noda, Y. Ohsumi, Autophagy in yeast demonstrated with proteinase-deficient mutants and conditions for its induction, J Cell Biol, Vol. 119, 1992, 301-311 3 N. Mizushima, T. Noda, T. Yoshimori, Y. Tanaka, T. Ishii, M.D. George, A protein conjugation system essential for autophagy, Nature, Vol. 395, 1998, 395-398 4 Y. Ichimura, T. Kirisako, T. Takao, Y. Satomi, Y. Shimonishi, N. Ishihara, A ubiquitin-like system mediates protein lipidation, Nature, Vol. 408, 2000, 488-492 5 S. Radonjic-Hoesli, X. Wang, E. de Graauw, C. Stoeckle, B. Styp-Rekowska, R. Hlushchuk, Eosinophil cytolysis requires the RIPK3-MLKL signaling pathway and is counter-regulated by autophagy, J Allergy Clin Immunol, Vol. 140, 2017, 1632-1642 6 G.Y. Ban, D.L. Pham, T.H. Trinh, S.I. Lee, D.H. Suh, E.M. Yang, Autophagy mechanisms in sputum and peripheral blood cells of patients with severe asthma: a new therapeutic target, Clin Exp Allergy, Vol. 46, 2016, 48-59 7 J.D. Dickinson, Y. Alevy, N.P. Malvin, K.K. Patel, S.P. Gunsten, M.J. Holtzman, IL13 activates autophagy to regulate secretion in airway epithelial cells, Autophagy, Vol. 12, 2016, 397-409 8 A.A. Zeki, S. Ott, K. Sandhu, S. Ghavami, N.J. Kenyon, The complex roles of endoplasmic reticulum stress and autophagy in modulating Eotaxin-3 production and secretion from human airway epithelial cells, Am J Respir Crit Care Med, Vol. 189, 2014, A5683 9 Z. Cao, P. Pan, H. Tan, Q. Tan, Z. Wang, X. Su, Anti-nerve growth factor antibody reduces airway hyperresponsiveness in a mouse model of asthma by down-regulating the level of autophagy in lungs, Zhonghua Jie He He Hu Xi Za Zhi, Vol. 37, 2014, 507-511 10 I.-H.
Update on epigenetics in allergic disease Harb, Hani, MSc; Renz, Harald, MD
Journal of allergy and clinical immunology,
01/2015, Letnik:
135, Številka:
1
Journal Article
Recenzirano
Chronic inflammatory diseases, including allergies and asthma, are the result of complex gene-environment interactions. One of the most challenging questions in this regard relates to the biochemical ...mechanism of how exogenous environmental trigger factors modulate and modify gene expression, subsequently leading to the development of chronic inflammatory conditions. Epigenetics comprises the umbrella of biochemical reactions and mechanisms, such as DNA methylation and chromatin modifications on histones and other structures. Recently, several lifestyle and environmental factors have been investigated in terms of such biochemical interactions with the gene expression–regulating machinery: allergens; microbes and microbial compounds; dietary factors, including vitamin B12, folic acid, and fish oil; obesity; and stress. This article aims to update recent developments in this context with an emphasis on allergy and asthma research.
...anti-IgA was added to the further fractionated preparation to precipitate all IgA molecules, and the Ishizakas found that all reaginic activity in the further fractionated preparation remained in ...the supernatant. ...in these 3 articles they concluded that the activity was associated with an impurity often contained in the crude serum IgA fraction, which was not detectable by using the usual immunochemical methods at that time and that the concentration of the carrier protein of the reaginic activity in the original serum was less than 1 μg/mL. ...approaches were impossible for identification of a minor component of the serum. ...the Ishizakas changed their strategy to prepare rabbit antibodies against this impure fraction showing reaginic activity, in which known immunoglobulin classes were removed. ...they were able to identify IgE as a unique protein using newly prepared anti-human IgE.7 As all of us know, the discovery of IgE was completed by the discovery of a patient with IgE myeloma by Johansson.8 The triumph of the Ishizakas' discovery of IgE went to the 2 articles published in the Journal of Immunology.1,2 However, it would not have been possible to identify IgE without their preceding studies described in the 3 articles, which were published in the Journal of Allergy.3-5 Studies on “physicochemical properties of reaginic antibody” seem to have been seamlessly performed in a logical fashion.
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