Mcclearydonovan6031

Previously, we demonstrated in test and validation cohorts that type I IFN (T1IFN) activity can predict non-response to tumor necrosis factor inhibitors (TNFi) in rheumatoid arthritis (RA). In this study, we examine the biology of non-classical and classical monocytes from RA patients defined by their pre-biologic treatment T1IFN activity. We compared single cell gene expression in purified classical (CL, n = 342) and non-classical (NC, n = 359) monocytes. learn more In our previous work, RA patients who had either high IFNβ/α activity (>1.3) or undetectable T1IFN were likely to have EULAR non-response to TNFi. In this study comparisons were made among patients grouped according to their pre-biologic treatment T1IFN activity as clinically relevant "T1IFN undetectable (T1IFN ND) or IFNβ/α >1.3" (n = 9) and "T1IFN detectable but IFNβ/α ≤ 1.3" (n = 6). In addition, comparisons were made among patients grouped according to their T1IFN activity itself "T1IFN ND," "T1IFN detected and IFNβ/α ≤ 1.3," and "IFNβ/α >1.3." Major differences in gene expression were apparent in principal component and unsupervised cluster analyses. CL monocytes from the T1IFN ND or IFNβ/α >1.3 group were unlikely to express JAK1 and IFI27 (p 1.3 groups included MYD88, CD86, IRF1, and IL8. This work could suggest key pathways active in biologically defined groups of patients, and potential therapeutic strategies for those patients unlikely to respond to TNFi.Yellow Fever (YF) vaccination is suggested to induce a large number of adverse events (AE) and suboptimal responses in patients with autoimmune diseases (AID); however, there have been no studies on 17DD-YF primary vaccination performance in patients with AID. This prospective non-interventional study conducted between March and July, 2017 assessed the safety and immunogenicity of planned 17DD-YF primary vaccination in patients with AID. Adult patients with AID (both sexes) were enrolled, along with healthy controls, at a single hospital (Vitória, Brazil). Included patients were referred for planned vaccination by a rheumatologist; in remission, or with low disease activity; and had low level immunosuppression or the attending physician advised interruption of immunosuppression for safety reasons. The occurrence of AE, neutralizing antibody kinetics, seropositivity rates, and 17DD-YF viremia were evaluated at various time points (day 0 (D0), D3, D4, D5, D6, D14, and D28). Individuals evaluated (n = 278), incl primary vaccination is safe and immunogenic in patients with AID.[This corrects the article DOI 10.3389/fimmu.2017.01519.].Thrombotic microangiopathy (TMA) has different etiological causes, and not all of them are well understood. In atypical hemolytic uremic syndrome (aHUS), the TMA is caused by the complement dysregulation associated with pathogenic mutations in complement components and its regulators. Here, we describe a pediatric patient with aHUS in whom the relatively benign course of the disease confused the initial diagnosis. A previously healthy 8-year-old boy developed jaundice, hematuria, hemolytic anemia, thrombopenia, and mild acute kidney injury (AKI) in the context of a diarrhea without hypertension nor oliguria. Spontaneous and complete recovery was observed from the third day of admission. Persistent low C3 plasma levels after recovery raised the suspicion for aHUS, which prompted clinicians to discard the initial diagnosis of Shigatoxin-associated HUS (STEC-HUS). A thorough genetic and molecular study of the complement revealed the presence of an isolated novel pathogenic C3 mutation. The relatively benign clinical course of the disease as well as the finding of a de novo pathogenic C3 mutation are remarkable aspects of this case. The data are discussed to illustrate the benefits of identifying the TMA etiological factor and the relevant contribution of the MCP aHUS risk polymorphism to the disease severity.Neutrophil extracellular traps (NETs) formation has been implicated in an increasing number of infectious and non-infectious pathologies. NETosis is a tightly regulated process; the end-stage and read-out is the formation of DNA strands extruded from the nuclei, and traditionally assessed by fluorescence microscopy. Since NETosis has emerged as a possible biomarker of the inflammatory process, there is a need for less time-consuming, consistent, and quantitative approaches to improve its application in clinical assessment of pro-inflammatory conditions. Imaging Flow Cytometry (IFC) combines features of conventional flow cytometry with qualitative power of fluorescence microscopy and has an added advantage of the capability of assessing the early processes leading up to extrusion of the DNA-scaffolded strands. We explored the optimal imaging-based tools that can be used to measure citrullination of H4 in early NETosis. IFC identified and quantified histone 4 citrullination (H4cit3) induced with several known NETosis stimuli (Ionophore, PMA, LPS, Hemin, and IL-8) following treatment periods ranging from 2 to 60 min. Its relationship with other alterations at nuclear and cellular level, such as nuclear decondensation and super-condensation, multi-lobulated nuclei vs. 1-lobe nuclei and cell membrane damage, were also quantified. We show that the early progress of the H4cit3 response in NETosis depends on the stimulus. Our method identifies fast (Ionophore and Hemin), intermediate and slow (PMA) inducers and shows that H4cit3 appears to have a limited contribution to both early LPS- and IL-8-induced NETosis. While this method is rapid and of a higher throughput compared to fluorescence microscopy, detection and quantification is limited to H4cit3-mediated nuclear events and is likely to be stimulus- and signaling pathway dependent.Early-life viral infections are responsible for pulmonary exacerbations that can contribute to disease progression in young children with cystic fibrosis (CF). The most common respiratory viruses detected in the CF airway are human rhinoviruses (RV), and augmented airway inflammation in CF has been attributed to dysregulated airway epithelial responses although evidence has been conflicting. Here, we exposed airway epithelial cells from children with and without CF to RV in vitro. Using RNA-Seq, we profiled the transcriptomic differences of CF and non-CF airway epithelial cells at baseline and in response to RV. There were only modest differences between CF and non-CF cells at baseline. In response to RV, there were 1,442 and 896 differentially expressed genes in CF and non-CF airway epithelial cells, respectively. The core antiviral responses in CF and non-CF airway epithelial cells were mediated through interferon signaling although type 1 and 3 interferon signaling, when measured, were reduced in CF airway epithelial cells following viral challenge consistent with previous reports.