Anti–Interleukin-23 Autoantibodies and Severe Infections This editorial describes the science behind a study of an autoimmune response against cytokines in persons with thymoma and severe infections. Figure 1 from the editorial illustrates interleukins 12 and 23 and the effects of anti–interleukin-23 autoantibodies. Interleukins 12 and 23 are produced mainly by myeloid cells on recognition of pathogen-associated molecular patterns (PAMPs) by pattern-recognition receptors (Panel A). On release, they stimulate T cells and other innate lymphoid populations such as natural killer cells and mucosal-associated invariant T cells, which then go on to produce immune-activating cytokines such as interferon-γ and interleukins 17 and 22 (Panel B). Autoantibodies against both interleukin-12 and interleukin-23 have been described, more often in patients with thymoma than in healthy persons or persons with autoimmune polyglandular syndrome type 1, but only anti–interleukin-23 autoantibodies seem to be clearly associated with opportunistic infections, whereas anti–interleukin-12 antibodies result only in a partial immune deficit (Panel C). Anti–interleukin-23 antibodies block the intracellular signaling downstream of receptors for interleukin-23, such as that mediated by signal transducer and activator of transcription 3 and 4 (STAT3 and STAT4), and block production of granulocyte–macrophage colony-stimulating factor (GM-CSF), interleukins 17 and 22, and interferon-γ (Panel D). IFN denotes interferon, IL interleukin, Th1 type 1 helper T cell, and Th17 type 17 helper T cell. Read the science behind the study in the editorial “Anti–Interleukin-23 Autoantibodies and Severe Infections” by Mihai G. Netea, M.D., Ph.D., and Frank van de Veerdonk, M.D., Ph.D., from Radboudumc and The University of Bonn: https://nej.md/43qpgVu
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📃Scientific paper: GLP-1 Receptor Signaling Differentially Modifies the Outcomes of Sterile vs Viral Pulmonary Inflammation in Male Mice Abstract: A number of disease states, including type 2 diabetes (T2D), are associated with an increased risk of pulmonary infection. Glucagon-like peptide-1 (GLP-1) receptor agonists are used to treat T2D and exert anti-inflammatory actions through a single, well-defined GLP-1 receptor (GLP-1R). Although highly expressed in the lung, little is known about the role of the GLP-1R in the context of pulmonary inflammation. Here we examined the consequences of gain or loss of GLP-1R activity in infectious and noninfectious lung inflammation. We studied wild-type mice treated with a GLP-1R agonist, and Glp1r(–/–) mice, in the setting of bleomycin-induced noninfectious lung injury and influenza virus infection. Loss of the GLP-1R attenuated the severity of bleomycin-induced lung injury, whereas activation of GLP-1R signaling increased pulmonary inflammation via the sympathetic nervous system. In contrast, GLP-1R agonism reduced the pathogen load in mice with experimental influenza virus infection in association with increased expression of intracellular interferon-inducible GTPases. Notably, the GLP-1 receptor agonist liraglutide improved the survival rate after influenza virus infection. Our results reveal context-dependent roles for the GLP-1 system in the response to lung injury. Notably, the therapeutic response of GLP-1R agonism in the setting of experimental influenza virus infection may have relevance for ongoing studies of GLP-1R agonism in people with T2D susceptible to vi... Discover the rest of the scientific article on es/iode ➡️https://etcse.fr/iz #influenza #science #health #medical #study #research #scientificpaper #scientificresearch
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Clinical Biochemist | Dual Master's in Digital Health and Public Health Management | COVID-19 Expert | Leader in Clinical Diagnostics | Published Scientist.
Since its discovery in 2019, coronavirus disease 2019 (COVID-2019) spans a wide clinical spectrum from the asymptomatic stage, mild infection, to severe pneumonia. In patients with COVID-2019, factors such as advanced age, diabetes, or hypertension are associated with a significantly increased risk of severe diseases and death. Of note, the mechanisms underlying differences in the risk and symptoms of COVID-2019 among different populations are still poorly characterized. Accordingly, it is imperative to elucidate potential pathophysiological mechanisms and develop targeted therapeutic approaches for COVID-2019 infection. N6-methyladenosine (m6A) is one of the most common modifications in mammalian RNA transcripts and is widely found in messenger RNAs and some non-coding RNAs. It has been reported that m6A methylation modifications are present in viral RNA transcripts, which are of great significance for the regulation of the viral life cycle. Furthermore, m6A methylation has recently been found to be strongly associated with COVID-2019 infection. Therefore, this article reviews recent advances in studies related to the role of m6A methylation in COVID-2019 infection.
m6A methylation: a potential key player in understanding and treating COVID-2019 infection - Cell Death Discovery
nature.com
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Comparative evaluation of four rapid diagnostic tests that detect human Trypanosoma cruzi-specific antibodies to support diagnosis of Chagas Disease in urban population of Argentina 🗣 Abstract Background: Chagas disease (CD), caused by the parasite Trypanosoma cruzi, is the most important endemic anthropozoonosis in Argentina. Since 2010, the World Health Organization has highlighted the urgent need to validate diagnostic systems that allow rapid detection of T. cruzi, infection in primary healthcare centers. Serological rapid diagnostic tests (RDTs) for T. cruzi, infection could be used to improve case management, as RDTs do not require specialized laboratories or highly trained staff to use them. We aimed to generate unbiased performance data of RDTs in Argentina, to evaluate their usefulness for improving T. cruzi, diagnosis rates. Methods and principal findings: This is a retrospective, laboratory-based, diagnostic evaluation study to estimate the clinical sensitivity/specificity of four commercially available RDTs for T. cruzi, using the Chagas disease diagnostic algorithm currently used in Argentina as the reference standard. In total, 400 serum samples were tested, 200 from individuals with chronic T. cruzi infection and 200 from individuals not infected with T. cruzi. All results were registered as the agreement of at least two operators who were blinded to the reference standard results. The sensitivity estimates ranged from 92.5-100% (95% confidence interval (CI) lower bound 87.9-98.2%); for specificity, the range was 76-96% (95% CI lower bound 69.5-92.3%). Most RDTs evaluated showed performances comparable with the reference standard method, showing almost perfect concordance (Kappa 0.76-0.92). Conclusions: Our study demonstrates that, under controlled laboratory conditions, commercially available RDTs for CD have a performance comparable to the Argentinian diagnostic algorithm, which is based on laboratory-based serological tests. For the next stage of our work, the RDTs will be evaluated in real-world settings. Articulo en completo 👉 https://lnkd.in/dUXKepu4
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Family practitioner at Smith Clinic and St Mary hospital
1moI admit that I did not read the research behind this , but after many years of being a physician I do have to ask . How much of this model is based on theory?