ACE2 and TMPRSS2 are key players on SARS-CoV-2 entry into host cells. However, it is still unclear whether expression levels of these factors could reflect disease severity. Here, a case–control study was conducted with 213 SARS-CoV-2 positive individuals where cases were defined as COVID-19 patients with respiratory distress requiring oxygen support (N = 38) and controls were those with mild to moderate symptoms of the disease who did not need oxygen therapy along the entire clinical course (N = 175). ACE2 and TMPRSS2 mRNA levels were evaluated in nasopharyngeal swab samples by RT-qPCR and logistic regression analyzes were applied to estimate associations with respiratory outcomes. ACE2 and TMPRSS2 levels positively correlated with age, which was also strongly associated with respiratory distress. Increased nasopharyngeal ACE2 levels showed a protective effect against this outcome (adjOR = 0.30; 95% CI 0.09–0.91), while TMPRSS2/ACE2 ratio was associated with risk (adjOR = 4.28; 95% CI 1.36–13.48). On stepwise regression, TMPRSS2/ACE2 ratio outperformed ACE2 to model COVID-19 severity. When nasopharyngeal swabs were compared to bronchoalveolar lavages in an independent cohort of COVID-19 patients under mechanical ventilation, similar expression levels of these genes were observed. These data suggest nasopharyngeal TMPRSS2/ACE2 as a promising candidate for further prediction models on COVID-19.

Dramatic changes in the environment and human lifestyle have been associated with the rise of various chronic complex diseases, such as inflammatory bowel disease (IBD). A dysbiotic gut microbiota has been proposed as a crucial pathogenic element, contributing to immune imbalances and fostering a proinflammatory milieu, which may be associated with disease relapses or even the initiation of IBD. In addition to representing important regulators of the mucosal immunity and the composition of the gut microbiota, food components have been shown to be potential environmental triggers of epigenetic modifications. In the context of chronic intestinal inflammation, dietary habits and specific food components have been implicated as important modulators of epigenetic mechanisms, including DNA methylation, which may predispose a person to the increased risk of the initiation and evolution of IBD. This review provides novel insights about how dietary factors may interact with the intestinal mucosa and modulate immune homeostasis by shaping the intestinal ecosystem, as well as the potential influence of diet in the etiopathogenesis and management of IBD.

The chronic inflammatory process underlying inflammatory bowel disease (IBD), comprising Crohn’s disease and ulcerative colitis, derives from the interplay of several components in a genetically susceptible host. These components include environmental elements and gut microbiota a dysbiosis. For decades, immune abnormalities have been investigated as critically important in IBD pathogenesis, and attempts to develop effective therapies have predominantly targeted the immune system. Nevertheless, immune events represent only one of the constituents contributing to IBD pathogenesis within the context of the complex cellular and molecular network underlying chronic intestinal inflammation. These factors need to be appreciated within the milieu of non-immune components. Damage-associated molecular patterns (DAMPs), which are essentially endogenous stress proteins expressed or released as a result of cell or tissue damage, have been shown to act as direct pro-inflammatory mediators. Excessive or persistent signalling mediated by such molecules can underlie several chronic inflammatory disorders, including IBD. The release of endogenous DAMPs amplifies the inflammatory response driven by immune and non-immune cells and promotes epigenetic reprogramming in IBD. The effects determine pathologic changes, which may sustain chronic intestinal inflammation and also underlie specific disease phenotypes. In addition to highlighting the potential use of DAMPs such as calprotectin as biomarkers, research on DAMPs may reveal novel mechanistic associations in IBD pathogenesis and is expected to uncover putative therapeutic targets.

Arboviruses pose a major threat throughout the world and represent a great burden in tropical countries of South America. Although generally associated with moderate febrile illness, in more severe cases they can lead to neurological outcomes, such as encephalitis, Guillain-Barré syndrome, and Congenital Syndromes. In this context astrocytes play a central role in production of inflammatory cytokines, regulation of extracellular matrix, and control of glutamate driven neurotoxicity in the central nervous system. Here, we presented a comprehensive genome-wide transcriptome analysis of human primary astrocytes infected with Chikungunya, Mayaro, Oropouche, or Zika viruses. Analyses of differentially expressed genes (DEGs), pathway enrichment, and interactomes have shown that Alphaviruses up-regulated genes related to elastic fiber formation and N-glycosylation of glycoproteins, with down-regulation of cell cycle and DNA stability and chromosome maintenance genes. In contrast, Oropouche virus up-regulated cell cycle and DNA maintenance and condensation pathways while down-regulated extracellular matrix, collagen metabolism, glutamate and ion transporters pathways. Zika virus infection only up-regulated eukaryotic translation machinery while down-regulated interferon pathways. Reactome and integration analysis revealed a common signature in down-regulation of innate immune response, antiviral response, and inflammatory cytokines associated to interferon pathway for all arboviruses tested. Validation of interferon stimulated genes by reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) corroborated our transcriptome findings. Altogether, our results showed a co-evolution in the mechanisms involved in the escape of arboviruses to antiviral immune response mediated by the interferon (IFN) pathway.

Human retroelements (HERVs) are retroviral origin sequences fixed in the human genome. HERVs induction is associated with neurogenesis, cellular development, immune activation, and neurological disorders. Arboviruses are often associated with the development of encephalitis. The interplay between these viruses and HERVs has not been fully elucidated. In this work, we analyzed RNAseq data derived from infected human primary astrocytes by Zika (ZikV), Mayaro (MayV), Oropouche (OroV) and Chikungunya (ChikV) viruses, and evaluated the modulation of HERVs and their nearby genes. Our data show common HERVs expression modulation by both alphaviruses, suggesting conserved evolutionary routes of transcription regulation. A total of 15 HERVs were co-modulated by the four arboviruses, including the highly upregulated HERV4_4q22. Data on the upregulation of genes nearby to these elements in ChikV, MayV and OroV infections were also obtained, and interaction networks were built. The upregulation of 14 genes common among all viruses was observed in the networks, and 93 genes between MayV and ChikV. These genes are related to cellular processes such as cellular replication, cytoskeleton, cell vesicle traffic and antiviral response. Together, our results support the role of HERVs induction in the transcription regulation process of genes during arboviral infections.

Background Immunoglobulin A (IgA) is responsible for protection against infections of the respiratory and gastrointestinal tracts, and selective IgA deficiency (SIgAD) is the most common humoral immunodeficiency. It is speculated that its occurrence may predispose to the development of systemic lupus erythematosus (SLE). Objectives To study the prevalence of SIgAD in patients with juvenile SLE (JSLE) in the Adolescent Rheumatology Clinic from the Hospital Universitário Clementino Fraga Filho – Universidade Federal do Rio de Janeiro, and compare, between the groups of patients with and without SIgAD, the age and the clinical manifestations at the diagnosis of JSLE; the index of disease activity at the time of analysis of levels of IgA; and family history of rheumatic diseases, autoimmune and/or congenital immunodeficiencies. Methods We carried out a review of medical records of 63 patients diagnosed with JSLE according to the criteria of the American College of Rheumatology (ACR). Plasma levels of IgA in these patients were measured by nephelometry and were considered low when less than 70mg/dL. The demographic data, the clinical and laboratory profiles and family history were obtained by review of medical records. Results The SIgAD was detected in 3 of 63 patients (4.8%). The clinical and laboratory profiles of the group with SIgAD was not significantly different from the group without SIgAD, not being observed a higher incidence of infections in this group of patients. Conclusions It was noted a higher prevalence of SIgAD in patients with JSLE compared to the general population, but no significant clinical or laboratorial difference was observed between the patients with and without SIgAD. References JT Cassidy, RK Kitson & CL Selby. Selective IgA deficiency in children and adults with systemic lupus erythematosus. Lupus 2007; 16(8):647-650. Disclosure of Interest None Declared

Background Uveitis is a common manifestation of rheumatic diseases with a broad spectrum of clinical presentation. It can be acute or chronic, affect any part of the uveal tract, can occur before or after the diagnosis of the associated rheumatic condition and can progress with severe complications. In Juvenile Idiopathic Arthritis (JIA) it tipically involves the anterior chamber, is frequently oligosymptomathic and carries a high rate of complications. Objectives Analyze the course and the development of uveitis associated with rheumatic diseases in outpatients of the Rheumatic Clinic of Hospital Universitário Clementino Fraga Filho (HUCFF) at Universidade Federal do Rio de Janeiro between 2000 and 2010. Methods We conducted a retrospective study based on review of medical records of 37 patients in the Rheumatology Clinic of the HUCFF. The selected patients had a previous diagnosis of uveitis and were enrolled to our service between 2000 and 2010. Results Twenty-six patients (70,3%) presented with a rheumatic disease, while 11 (29,7%) patients had isolated uveits. The most frequent diagnosis was JIA (56,8%), followed by idiopathic uveitis (29,7%) and the spondyloarthritis was diagnosed in 8,1%. In most cases, the uveitis presented in the course of the underlying disease (56,8%), as it was the involvement of the anterior chamber of the eye (70,3%). Of these 37 patients, there were a total of 57 affected eyes and 92% had a chronic presentation. The presence of antinuclear antibodies (ANA) was associated with higher frequency of uveitis and most patients with positive ANA developed complications (65%). The most frequent complications were cataract (30.2%) and posterior synechiae (13.2%). All patients who were on biological therapy presented some complication, what could be explained by the greater severity of uveitis in patients who require the use of these medications. Conclusions Juvenile idiopathic arthritis-related uveitis accounts for the majority of identifiable causes of childhood onset uveitis. The characteristics of uveitis associated with rheumatic diseases observed in this study were similar to those found by other authors. The rate and spectrum of vision threatening complications of pediatric uveitis are significant and the authors emphasize the importance of regular eye evaluation in rheumatic diseases. Disclosure of Interest None Declared

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