It has been recognized for centuries that allergic disease runs in families, implying a role for genetic factors in determining individual susceptibility. More recently, a range of evidence shows that many of these genetic factors, together with in utero environmental exposures, lead to the development of allergic disease through altered immune and organ development. Environmental exposures during pregnancy including diet, nutrient intake and toxin exposures can alter the epigenome and interact with inherited genetic and epigenetic risk factors to directly and indirectly influence organ development and immune programming. Understanding of these factors will be essential in identifying at-risk individuals and possible development of therapeutic interventions for the primary prevention of allergic disease. In this review, we summarize the evidence that suggests allergic disease begins in utero, together with possible mechanisms for the effect of environmental exposures during pregnancy on allergic disease risk, including epigenetics.

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A majority of SARS-CoV-2 recoverees develop only mild-to-moderate symptoms, while some remain completely asymptomatic. Although viruses, including SARS-CoV-2, may evade host immune responses by epigenetic mechanisms including DNA methylation, little is known about whether these modifications are important in defence against and healthy recovery from COVID-19 in the host. To this end, epigenome-wide DNA methylation patterns from COVID-19 convalescents were compared to uninfected controls from before and after the pandemic. Peripheral blood mononuclear cell (PBMC) DNA was extracted from uninfected controls, COVID-19 convalescents, and symptom-free individuals with SARS-CoV-2-specific T cell-responses, as well as from PBMCs stimulated in vitro with SARS-CoV-2. Subsequently, the Illumina MethylationEPIC 850K array was performed, and statistical/bioinformatic analyses comprised differential DNA methylation, pathway over-representation, and module identification analyses. Differential DNA methylation patterns distinguished COVID-19 convalescents from uninfected controls, with similar results in an experimental SARS-CoV-2 infection model. A SARS-CoV-2-induced module was identified in vivo , comprising 66 genes of which six ( TP53, INS, HSPA4, SP1, ESR1, and FAS ) were present in corresponding in vitro analyses. Over-representation analyses revealed involvement in Wnt, muscarinic acetylcholine receptor signalling, and gonadotropin-releasing hormone receptor pathways. Furthermore, numerous differentially methylated and network genes from both settings interacted with the SARS-CoV-2 interactome. Altered DNA methylation patterns of COVID-19 convalescents suggest recovery from mild-to-moderate SARS-CoV-2 infection leaves longstanding epigenetic traces. Both in vitro and in vivo exposure caused epigenetic modulation of pathways thataffect odour perception. Future studies should determine whether this reflects host-induced protective antiviral defense or targeted viral hijacking to evade host defence.

Background: Immunomodulatory effects of sublingual immunotherapy on systemic and mucosal mediators in allergic children are largely unexplored. The aim of this study was to investigate allergy-related cytokine and chemokine levels, as well as IgA-responses upon a 3-year treatment with timothy grass pollen sublingual immunotherapy in children with allergic rhinoconjunctivitis.Methods: From children included in the GRAZAX ® Asthma Prevention study, blood and saliva samples were analyzed at inclusion, after 3 years of treatment, and 2 years after treatment ending. By means of Luminex and ELISA methodologies, allergy-related cytokines and chemokines were measured in plasma samples and allergen-stimulated peripheral blood mononuclear cell supernatants. Furthermore, studies of total, secretory, and Phl p 1-specific salivary IgA antibodies were performed using the same methods.Results: GRAZAX ® -treated children exhibited significantly higher levels of Phl p 1specific salivary IgA and serum IgG 4 , along with significantly lower skin prick test positivity, after 3 years of treatment and 2 years after treatment cessation.Additionally, plasma levels of the Th1-associated chemokines CXCL10 and CXCL11 were significantly higher in treated than untreated children at these time points.Timothy-induced ratios of IL-5/IL-13 over IFN-γ were significantly decreased after 3 years with active treatment, as were symptoms of allergic rhinitis in terms of both severity and visual analogue scale scores. However, no consistent correlations were found between the clinical outcomes and immunologic parameters. Conclusion: Phleum pratense sublingual immunotherapy in grass pollen allergic children modulates the immune response in the oral mucosa as well as systemically-by increasing Th1-responses, decreasing Th2-responses, and inducing immunoregulatory responses-all signs of tolerance induction. | 523 HUOMAN et Al.