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El reservorio latente de VIH-1, principalmente en los linfocitos T CD4+, es responsable de que la terapia antirretroviral (TAR) no consiga la eliminación completa del virus en los individuos infectados por VIH. Los inhibidores de tirosina kinasas (ITKs) se usan con éxito en clínica para tratar la leucemia mieloide crónica (LMC). Nuestro grupo describió previamente que los linfocitos T CD4+ de pacientes con LMC en tratamiento con ITKs como dasatinib eran resistentes a la infección por VIH-1 ex vivo. El principal mecanismo de esta actividad antiviral fue debido a la inhibición de la fosforilación del factor antiviral SAM domain HD domain-containing protein 1 (SAMHD1), lo cual preservaba la actividad contra el VIH-1 de este factor de restricción. Aproximadamente, al 50% del total de pacientes con LMC que alcanzan respuesta molecular profunda (RPM), se les puede retirar con seguridad el tratamiento de ITKs sin recaída molecular de su enfermedad. Así, se ha especulado que los ITKs podrían inducir una potente respuesta antileucémica que permanece en la mayoría de los pacientes, al menos un año después de la retirada del tratamiento. En este estudio, nuestro primer objetivo fue analizar la susceptibilidad a la infección de linfocitos T CD4+ de pacientes con LMC en tratamiento con ITKs. Observamos que posteriormente a la activación in vitro SAMHD1 se fosforilaba en los linfocitos T CD4+ aislados de pacientes con LMC a quienes se les había retirado el tratamiento un año antes. A pesar de que los linfocitos T CD4+ de estos pacientes eran aparentemente susceptibles a la infección por VIH-1, el tratamiento previo con ITKs redujo la frecuencia de la integración proviral cuando estas células fueron infectadas ex vivo, en comparación con células aisladas de donantes sanos no tratados. Esta menor susceptibilidad a la infección se asocia a un aumento de la actividad citotóxica mediada por NKs. Este aumento de la actividad citotóxica también fue observado en linfocitos T CD8+ TCRγδ. Un objetivo adicional fue evaluar el impacto de dasatinib en el reservorio de VIH en individuos infectados con VIH-1 que padecían LMC y que estaban simultáneamente en tratamiento con TAR y dasatinib. Debido a la baja incidencia estimada de infección por VIH-1 y LMC, tres individuos fueron reclutados en España y Alemania. El tamaño y composición del reservorio en los linfocitos de sangre periférica de estos individuos fue analizado en comparación con individuos infectados por VIH-1 en tratamiento con TAR y viremia indetectable. En los pacientes tratados con TAR y dasatinib se redujo la frecuencia de células latentemente infectadas, la reactivación de provirus y la fosforilación de SAMHD1. Los niveles plasmáticos de la citoquina homeostática IL-7 y las subpoblaciones efectoras de linfocitos T CD4+ TEM y TEMRA en sangre periférica también estaban reducidas. En conclusión, el tratamiento con ITKs induce una potente respuesta antileucémica que podría tener también efectos antivirales frente al VIH, sugiriendo que el uso de ITKs en individuos infectados con VIH podría generar una respuesta antiviral sostenida que interferiría con la replicación viral y la dinámica del reservorio del VIH-1. Finalmente, el tratamiento con dasatinib de individuos infectados con VIH-1 como adyuvante de TAR podría alterar la reactivación y el recambio homeostático del reservorio, lo cual podría tener un impacto positivo al reducir su tamaño y, posiblemente, favorecer su eliminación.

Introduction: Few studies have investigated glaucoma biomarkers in aqueous humor and tear and have found elevations of proinflammatory cytokines in patients with primary open-angle glaucoma (POAG) and pseudoexfoliative glaucoma (PXG). In this study, we investigate differences in inflammatory cytokines between POAG and PXG patients to find specific disease biomarkers. Methods: For this purpose, tear and aqueous humor samples of 14 eyes with POAG and 15 eyes with PXG undergoing cataract surgery were immunoassayed for 27 proinflammatory cytokines. The concentrations of cytokines in tear and aqueous humor and their association with clinical variables were analyzed, correlated, and compared between the groups. Results: We found that the levels of three cytokines differed significantly in the aqueous humor of POAG and PXG patients: IL-12 and IL-13 were higher in the POAG group, while monocyte chemoattractant protein-1 (monocyte chemotactic and activating factor) was higher in the PXG group. The number of topical hypotensive medications was correlated with diminished levels of two cytokines (IL-7 and basic fibroblast growth factor) in aqueous humor in the POAG group and with diminished levels of IL-12 in tear in the PXG group. Conclusion: We conclude that both POAG and PXG show elevated concentrations of proinflammatory cytokines in tear and aqueous humor that could be used as biomarkers for these types of glaucoma and that the concentrations in aqueous humor of three cytokines, IL-12, IL-13, and monocyte chemoattractant protein-1 (monocyte chemotactic and activating factor), could be used to differentiate POAG and PXG.

Neuroinflammation is a process related to the onset of neurodegenerative diseases; one of the hallmarks of this process is microglial reactivation and the secretion by these cells of proinflammatory cytokines such as TNFα. Numerous studies report the relationship between neuroinflammatory processes and exposure to anthropogenic air pollutants, but few refer to natural pollutants. Volcanoes are highly inhabited natural sources of environmental pollution that induce changes in the nervous system, such as reactive astrogliosis or the blood-brain barrier breakdown in exposed individuals; however, no neuroinflammatory event has been yet defined. To this purpose, we studied resting microglia, reactive microglia, and TNFα production in the brains of mice chronically exposed to an active volcanic environment on the island of São Miguel (Azores, Portugal). For the first time, we demonstrate a proliferation of microglial cells and an increase in reactive microglia, as well an increase in TNFα secretion, in the central nervous system of individuals exposed to volcanogenic pollutants. This research was supported by the Universidad de Alicante VIGROB-186.

Background Neuromyelitis optica spectrum disorder (NMOSD), an autoimmune astrocytopathy, may share common clinico-radiological features with Wernicke's encephalopathy (WE). A variant of NMOSD, known as area postrema syndrome (APS), that presents with intractable hiccups and associated vomiting, might lead to the depletion of nutrients if not detected and treated early. Autoimmune thyroid disorders (i.e., Graves’ disease) may be associated with NMOSD. Rarely, thyrotoxicosis can give rise to thiamine depletion and WE. Case presentation Here, we present a case of untreated hyperthyroidism in an Indian female who presented with thyrotoxicosis and later developed WE, possibly also contributed by NMOSD (APS)-induced recurrent vomiting. The patient recovered with antithyroid drugs, parenteral thiamine, and immunomodulatory therapy. The possible pathogenic mechanisms have been discussed. Conclusion Our case establishes the importance of considering NMOSD variants in metabolic encephalopathy, especially if neuroimaging is suggestive and in the backdrop of another autoimmune disorder.

Wnt signalling pathways have been reported to be involved in thymus development but their precise role in the development of both thymic epithelium (TE) and thymocytes is controversial. Herein, we examined embryonic, postnatal and adult thymi of mice with a specific deletion of β-catenin gene in FoxN1+ thymic epithelial cells (TECs). Together with a high postnatal mouse mortality, the analysis showed severe thymic hypocellularity, largely due an important reduction in numbers of developing thymocytes, and delayed, partially blocked maturation of mutant TECs. Affected TECs included largely cortical (c) TEC subsets, such as immature MTS20+ TECs, Ly51+ cTECs and a remarkable, rare Ly51+MTS20+MHCIIhi cell subpopulation previously reported to contain thymic epithelial progenitor cells (TEPCs) (Ulyanchenko et al., Cell Rep 14:2819–2832, 2016). In addition, altered postnatal organization of mutant thymic medulla failed to organize a unique, central epithelial area. This delayed maturation of TE cell components correlated with low transcript production of some molecules reported to be masters for TEC maturation, such as EphB2, EphB3 and RANK. Changes in the thymic lymphoid component became particularly evident after birth, when molecules expressed by TECs and involved in early T-cell maturation, such as CCL25, CXCL12 and Dll4, exhibited minimal values. This represented a partial blockade of the progression of DN to DP cells and reduced proportions of this last thymocyte subset. At 1 month, in correlation with a significant increase in transcript production, the DP cell percentage increased in correlation with a significant fall in the number of mature TCRαβhi thymocytes and peripheral T lymphocytes.

Spanish Collaboration on Endocarditis—Grupo de Apoyo al Manejo de la Endocarditis Infecciosa en España (GAMES)., [Background] Studies investigating the impact of cardiogenic shock (CS) on endocarditis are lacking., [Methods] Prospectively collected cohort from 35 Spanish centers (2008-2018). Logistic regression analyses were performed to identify risk factors for developing CS and predictors of mortality., [Results] Among 4856 endocarditis patients, 1652 (34%) had acute heart failure (AHF) and 244 (5%) CS. Compared with patients without AHF and AHF but no CS, patients with CS presented higher rates of surgery (40.5%, 52.5%, and 68%; P < .001) and in-hospital mortality (16.3%, 39.1%, and 52.5%). Compared with patients with septic shock, CS patients presented higher rates of surgery (42.5% vs 68%; P < .001) and lower rates of in-hospital and 1-year mortality (62.3% vs 52.5%, P = .008, and 65.3% vs 57.4%, P = .030). Severe aortic and mitral regurgitation (OR [95% CI], 2.47 [1.82-3.35] and 3.03 [2.26-4.07]; both P < .001), left-ventricle ejection fraction, [Conclusions] AHF is common among patients with endocarditis. CS is associated with high mortality and should be promptly identified and assessed for cardiac surgery., This work was supported by the Ministerio de Sanidad y Consumo of Spain (grant number FIS NCT00871104; Instituto de Salud Carlos III). Institut d’Investigacions Biomèdiques Pi i Sunyer (IDIBAPS) provided J. M. M. with a persobal IDIBAPS 80:20 research grant during 2017–2021. M. H. M. held a Rio Hortega Research Grant (CM17/00062) from the Instituto de Salud Carlos III” and the Ministerio de Economia y Competitividad, Madrid (Spain) in 2018–2020.

Background: Non-infectious non-anterior uveitis (NINA) is a sight-threatening condition that often requires immunomodulatory drugs (IMDs) for its management. Objectives: To evaluate the published evidence regarding the use of IMDs in adult patients with NINA uveitis including intermediate (IU) and posterior uveitis (PU), panuveitis (PanU) and macular edema (ME). Methods: We performed a systematic literature review. Search strategies were designed for Medline, Embase, and Cochrane Libraries for articles up to 2019 to evaluate the efficacy and safety of the IMDs. A quality assessment was performed using the Jadad Scale. Results: Nineteen randomized clinical trials were selected from the 1,103 articles retrieved. Characteristics of patients, treatment dosages and outcome measures were heterogeneous. The outcomes most frequently analyzed were visual acuity (VA), macular thickness and vitreous haze (VH). Different IMDs were used at their usual dosages. Methotrexate (MTX), micophenolate mofetil, cyclosporine A (CsA), tacrolimus, adalimumab and sarilumab were effective in NINA uveitis. Rituximab combined with MTX was effective in PU. Interferon-β was superior to MTX, albeit with more adverse events in IU with ME. CsA was similar to cyclophosphamide (Cyc) in Behçet uveitis. Tacrolimus was safer and similar to CsA. Cyc was effective in serpiginoid choroiditis, but when combined with azathioprine in PU, but did not improve VA. Secukinumab did not prevent NINA uveitis recurrences, although intravenously it showed a higher response rate than when used subcutaneously. Daclizumab did not show any benefits in Behçet NINA uveitis. Conclusion: Several IMDs and their combinations can be useful in treating NINA uveitis. The available studies were heterogeneous regarding patient characteristics and outcomes. Sin financiación 5.532 JCR (2020) Q2, 7/34 Rheumatology 1.955 SJR (2020) Q1, 6/122 Anesthesiology and Pain Medicine No data IDR 2020 UEM

COVID-19 is an infectious disease caused by the SARS-CoV-2 virus that can affect lung physiology encompassing a wide spectrum of severities, ranging from asymptomatic and mild symptoms to severe and fatal cases; the latter including massive neutrophil infiltration, stroke and multiple organ failure. Despite many recents findings, a clear mechanistic description underlying symptomatology is lacking. In this article, we thoroughly review the available data involving risk factors, age, gender, comorbidities, symptoms of disease, cellular and molecular mechanisms and the details behind host/pathogen interaction that hints at the existence of different pathophysiological mechanisms of disease. There is clear evidence that, by targeting the angiotensin-converting enzyme II (ACE2) –its natural receptor–, SARS-CoV-2 would mainly affect the reninangiotensin-aldosterone system (RAAS), whose imbalance triggers diverse symptomatology-associated pathological processes. Downstream actors of the RAAS cascade are identified, and their interaction with risk factors and comorbidities are presented, rationalizing why a specific subgroup of individuals that present already lower ACE2 levels is particularly more susceptible to severe forms of disease. Finally, the notion of endotype discovery in the context of COVID-19 is introduced. We hypothesize that COVID-19, and its associated spectrum of severities, is an umbrella term covering different pathophysiological mechanisms (endotypes). This approach should dramatically accelerate our understanding and treatment of disease(s), enabling further discovery of pathophysiological mechanisms and leading to the identification of specific groups of patients that may benefit from personalized treatments. Fil: Goldin, Carla Jimena. Fundación para la Investigación en Infectología Infantil; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Vázquez, Ramiro José. Fondazione Istituto Italiano di Tecnologia; Italia. Early Drug Development Group; Francia Fil: Polack, Fernando Pedro. Fundación para la Investigación en Infectología Infantil; Argentina Fil: Álvarez Paggi, Damián Jorge. Fundación para la Investigación en Infectología Infantil; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina

Gaucher disease (GD) is caused by pathogenic mutations in GBA1, the gene that encodes the lysosomal enzyme β-glucocerebrosidase. Until now, treatments for GD cannot completely reverse bone problems. The aim of this work was to evaluate the potential of MSCs from GD patients (GD MSCs) to differentiate towards the osteoblast (GD Ob) and adipocyte (GD Ad) lineages, and their role in osteoclastogenesis. We observed that GD Ob exhibited reduced mineralization, collagen deposition and alkaline phosphatase activity (ALP), as well as decreased gene expression of RUNX2, COLA1 and ALP. We also evaluated the process of osteoclastogenesis and observed that conditioned media from GD MSCs supernatants induced an increase in the number of osteoclasts. In this model, osteoclastogenesis was induced by RANKL and IL-1β. Furthermore, results showed that in GD MSCs there was a promotion in NLRP3 and PPAR-γ gene expression. Adipogenic differentiation revealed that GD Ad had an increase in PPAR-γ and a reduced RUNX2 gene expression, promoting adipocyte differentiation. In conclusion, our results show that GD MSCs exhibited deficient GD Ob differentiation and increased adipogenesis. In addition, we show that GD MSCs promoted increased osteoclastogenesis through RANKL and IL-1β. These changes in GD MSCs are likely to contribute to skeletal imbalance observed in GD patients. Fil: Crivaro, Andrea Natalia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Estudios Inmunológicos y Fisiopatológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Estudios Inmunológicos y Fisiopatológicos; Argentina Fil: Bondar, Constanza María. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Estudios Inmunológicos y Fisiopatológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Estudios Inmunológicos y Fisiopatológicos; Argentina Fil: Mucci, Juan Marcos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Estudios Inmunológicos y Fisiopatológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Estudios Inmunológicos y Fisiopatológicos; Argentina Fil: Ormazabal, Maximiliano Emanuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Estudios Inmunológicos y Fisiopatológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Estudios Inmunológicos y Fisiopatológicos; Argentina Fil: Feldman, Ricardo A.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina Fil: Delpino, María Victoria. University of Maryland School of Medicine. Department of Microbiology and Immunology; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina Fil: Rozenfeld, Paula Adriana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Estudios Inmunológicos y Fisiopatológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Estudios Inmunológicos y Fisiopatológicos; Argentina

This multicenter cohort study investigated the differences between coronavirus disease 2019 (COVID-19) related symptoms and post-COVID symptoms between male and female COVID-19 survivors. Clinical and hospitalization data were collected from hospital medical records in a sample of individuals recovered from COVID-19 at five public hospitals in Spain. A predefined list of post-COVID symptoms was systematically assessed, but patients were free to report any symptom. Anxiety/depressive levels and sleep quality were also assessed. Adjusted multivariate logistic regressions were used to identify the association of sex with post-COVID related-symptoms. A total of 1969 individuals (age: 61, SD: 16 years, 46.4% women) were assessed 8.4 months after discharge. No overall significant sex differences in COVID-19 onset symptoms at hospital admission were found. Post-COVID symptoms were present in up to 60% of hospitalized COVID-19 survivors eight months after the infection. The number of post-COVID symptoms was 2.25 for females and 1.5 for males. After adjusting by all variables, female sex was associated with ≥3 post-COVID symptoms (adj OR 2.54, 95%CI 1.671–3.865, p < 0.001), the presence of post-COVID fatigue (adj OR 1.514, 95%CI 1.040–2.205), dyspnea (rest: adj OR 1.428, 95%CI 1.081–1.886, exertion: adj OR 1.409, 95%CI 1.109–1.791), pain (adj OR 1.349, 95%CI 1.059–1.720), hair loss (adj OR 4.529, 95%CI 2.784–7.368), ocular problems (adj OR 1.981, 95%CI 1.185–3.312), depressive levels (adj OR 1.606, 95%CI 1.002–2.572) and worse sleep quality (adj OR 1.634, 95%CI 1.097–2.434). Female sex was a risk factor for the development of some long-term post-COVID symptoms including mood disorders. Healthcare systems should consider sex differences in the management of long haulers.

[EN] CD160 is a member of the immunoglobulin superfamily with a pattern of expression mainly restricted to cytotoxic cells. To assess the functional relevance of the HVEM/CD160 signaling pathway in allogeneic cytotoxic responses, exon 2 of the CD160 gene was targeted by CRISPR/Cas9 to generate CD160 deficient mice. Next, we evaluated the impact of CD160 deficiency in the course of an alloreactive response. To that aim, parental donor WT (wild-type) or CD160 KO (knock-out) T cells were adoptively transferred into non-irradiated semiallogeneic F1 recipients, in which donor alloreactive CD160 KO CD4 T cells and CD8 T cells clonally expanded less vigorously than in WT T cell counterparts. This differential proliferative response rate at the early phase of T cell expansion influenced the course of CD8 T cell differentiation and the composition of the effector T cell pool that led to a significant decreased of the memory precursor effector cells (MPECs) / short-lived effector cells (SLECs) ratio in CD160 KO CD8 T cells compared to WT CD8 T cells. Despite these differences in T cell proliferation and differentiation, allogeneic MHC class I mismatched (bm1) skin allograft survival in CD160 KO recipients was comparable to that of WT recipients. However, the administration of CTLA-4.Ig showed an enhanced survival trend of bm1 skin allografts in CD160 KO with respect to WT recipients. Finally, CD160 deficient NK cells were as proficient as CD160 WT NK cells in rejecting allogeneic cellular allografts or MHC class I deficient tumor cells. CD160 may represent a CD28 alternative costimulatory molecule for the modulation of allogeneic CD8 T cell responses either in combination with costimulation blockade or by direct targeting of alloreactive CD8 T cells that upregulate CD160 expression in response to alloantigen stimulation. SI

Instituto de Salud Carlos III (ISCII; COV20/00108 y COV20/1144) Red Española de Investigación sobre el Sida (RD16/0025/0017, RD16/0025/0018 y RD16CIII/0002/0002) Centro de Investigación Biomédica en Red (CIBER) en Enfermedades Infecciosas (CB21/13/00044) ISCIII (CP14CIII/00010 y CP17CIII/00007) 38.637 JCR (2021) Q1, 4/94 Infectious Diseases 5.027 SJR (2021) Q1, 7/301 Infectious Diseases No data IDR 2020 UEM

We demonstrated a limited expression of Toll-like receptor 9 (TLR9) and interferon gamma (IFN-γ) production by T cells in patients with simple steatosis (SS). The limited expression of TLR9 on T cells was directly associated with lower liver necroinflammatory activity and fibrosis, and lower antrophometric and biochemical alterations of nonalcoholic fatty liver disease. Besides, co-stimulation of T cell activation via TLR9 induced a limited number of IFN-γ-producing CD8+ T cells in SS patients. Accordingly, these patients showed a low frequency of circulating type 1 CD8+ cells whereas additional pro-inflammatory signals may be responsible for the higher frequency observed at baseline in the context of steatohepatitis. Fil: Alegre, Nadia Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina Fil: García, Cecilia Claudia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina Fil: Billordo, Luis Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina Fil: Ameigeiras, Beatriz. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; Argentina Fil: Poncino, Daniel. Sanatorio Municipal Dr. Julio Méndez. Servicio de Gastroenterología; Argentina Fil: Benavides, Javier. Hospital Británico de Buenos Aires; Argentina Fil: Colombato, Luis. Hospital Británico de Buenos Aires; Argentina Fil: Cherñavsky, Alejandra Claudia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina

(1) Background: This study aimed to analyze if the serum albumin levels of hospitalized SARS-CoV-2 (COVID-19) patients on admission could predict

Fasciola hepatica is a fluke that infects livestock and humans causing fasciolosis, a zoonotic disease of increasing importance due to its worldwide distribution and high economic losses. The parasite regulates the host immune system by inducing a strong Th2 and regulatory T (Treg) cell immune response through mechanisms that might involve the expression or activity of heme-oxygenase-1 (HO-1), the rate-limiting enzyme in the catabolism of free heme that also has immunoregulatory and antioxidant properties. In this paper, we show that F. hepatica-infected mice upregulate HO-1 on peritoneal antigen-presenting cells (APC), which produce decreased levels of both reactive oxygen and nitrogen species (ROS/RNS). The presence of these cells was associated with increased levels of regulatory T cells (Tregs). Blocking the IL-10 receptor (IL-10R) during parasite infection demonstrated that the presence of splenic Tregs and peritoneal APC expressing HO-1 were both dependent on IL-10 activity. Furthermore, IL-10R neutralization as well as pharmacological treatment with the HO-1 inhibitor SnPP protected mice from parasite infection and allowed peritoneal APC to produce significantly higher ROS/RNS levels than those detected in cells from infected control mice. Finally, parasite infection carried out in gp91phox knockout mice with inactive NADPH oxidase was associated with decreased levels of peritoneal HO-1+ cells and splenic Tregs, and partially protected mice from the hepatic damage induced by the parasite, revealing the complexity of the molecular mechanisms involving ROS production that participate in the complex pathology induced by this helminth. Altogether, these results contribute to the elucidation of the immunoregulatory and antioxidant role of HO-1 induced by F. hepatica in the host, providing alternative checkpoints that might control fasciolosis. Agencia Nacional de Investigación e Innovación Programa de Desarrollo de las Ciencias Básicas

(1) Background: To analyze the incidence, clinical characteristics, use of procedures, and in-hospital outcomes in patients who developed pneumonia during their hospital admission according to sex and to the presence of type 2 diabetes mellitus (T2DM). (2) Methods: Retrospective cohort study using data from the Spanish National Hospital Discharge Database. Hospital-acquired pneumonia (HAP) was classed as non-ventilator HAP and ventilator-associated pneumonia (VAP). Separate analyses were performed for men and women with and without T2DM. Population subgroups were compared using propensity score matching. (3) Results: HAP was identified in 38,814 patients (24.07% with T2DM). The adjusted incidence of HAP was higher in patients with T2DM (both sexes) (IRR 1.28; 95% CI 1.25–1.31). The incidence of HAP was higher in men with T2DM than in women with T2DM (adjusted-IR 1.47; 95% CI 1.41–1.53). The incidence of HAP among T2DM patients increased over time. In-hospital mortality (IHM) was around 28% irrespective of T2DM status and sex. After adjusting for confounders and sex, VAP was associated to higher IHM among patients with T2DM (OR 2.09; 95% CI 1.7–2.57). (4) Conclusions: T2DM is associated with a higher risk of HAP, whose incidence increased over time. Men with T2DM have an almost 50% higher risk of HAP than women with T2DM. The probability of dying in the hospital was not associated with sex or T2DM.

Aging is the result of the deterioration of the homeostatic systems (nervous, endocrine, and immune systems), which preserve the organism’s health. We propose that the age-related impairment of these systems is due to the establishment of a chronic oxidative stress situation that leads to low-grade chronic inflammation throughout the immune system’s activity. It is known that the immune system weakens with age, which increases morbidity and mortality. In this context, we describe how the function of immune cells can be used as an indicator of the rate of aging of an individual. In addition to this passive role as a marker, we describe how the immune system can work as a driver of aging by amplifying the oxidative-inflammatory stress associated with aging (oxi-inflamm-aging) and inducing senescence in far tissue cells. Further supporting our theory, we discuss how certain lifestyle conditions (such as social environment, nutrition, or exercise) can have an impact on longevity by affecting the oxidative and inflammatory state of immune cells, regulating immunosenescence and its contribution to oxi-inflamm-aging.

Prediction of linear B cell epitopes is of interest for the production of antigen-specific antibodies and the design of peptide-based vaccines. Here, we present BCEPS, a web server for predicting linear B cell epitopes tailored to select epitopes that are immunogenic and capable of inducing cross-reactive antibodies with native antigens. BCEPS implements various machine learning models trained on a dataset including 555 linearized conformational B cell epitopes that were mined from antibody–antigen protein structures. The best performing model, based on a support vector machine, reached an accuracy of 75.38% ± 5.02. In an independent dataset consisting of B cell epitopes retrieved from the Immune Epitope Database (IEDB), this model achieved an accuracy of 67.05%. In BCEPS, predicted epitopes can be ranked according to properties such as flexibility, accessibility and hydrophilicity, and with regard to immunogenicity, as judged by their predicted presentation by MHC II molecules. BCEPS also detects if predicted epitopes are located in ectodomains of membrane proteins and if they possess N-glycosylation sites hindering antibody recognition. Finally, we exemplified the use of BCEPS in the SARS-CoV-2 Spike protein, showing that it can identify B cell epitopes targeted by neutralizing antibodies.

Despite the growing number of patients with persistent symptoms after acute SARS-CoV-2 infection, the pathophysiology underlying long-COVID is not yet well characterized, and there is no established therapy. We performed a deep immune profiling in nine patients with persistent symptoms (PSP), before and after a 4-day prednisone course, and five post-COVID-19 patients without persistent symptoms (NSP). PSP showed a perturbed distribution of circulating mononuclear cell populations. Symptoms in PSP were accompanied by a pro-inflammatory phenotype characterized by increased conventional dendritic cells and augmented expression of antigen presentation, co-stimulation, migration, and activation markers in monocytes. The adaptive immunity compartment in PSP showed a Th1-predominance, decreased naïve and regulatory T cells, and augmentation of the PD-1 exhaustion marker. These immune alterations reverted after the corticosteroid treatment and were maintained during the 4-month follow-up, and their normalization correlated with clinical amelioration. The current work highlights an immunopathogenic basis together with a possible role for steroids in the treatment for long-COVID.

Primary immunodeficiency diseases (PID), which are comprised of over 400 genetic disorders, occur when a component of the immune system is diminished or dysfunctional. Patients with PID who require immunoglobulin (IG) replacement therapy receive intravenous IG (IVIG) or subcutaneous IG (SCIG), each of which provides equivalent efficacy. We developed a cost-minimization model to evaluate costs of IVIG versus SCIG from the Spanish National Healthcare System perspective. The base case modeled the annual cost per patient of IVIG and SCIG for the mean doses (per current expert clinical practice) over 1 year in terms of direct (drug and administration) and indirect (lost productivity for adults and parents/guardians of pediatric patients) costs. It was assumed that all IVIG infusions were administered in a day hospital, and 95% of SCIG infusions were administered at home. Drug costs were calculated from ex-factory prices obtained from local databases minus the mandatory deduction. Costs were valued on 2018 euros. The annual modeled costs were €4,266 lower for patients with PID who received SCIG (total €14,466) compared with those who received IVIG (total €18,732). The two largest contributors were differences in annual IG costs as a function of dosage (– €1,927) and hospital administration costs (– €2,688). However, SCIG incurred training costs for home administration (€695). Sensitivity analyses for two dose-rounding scenarios were consistent with the base case. Our model suggests that SCIG may be a cost-saving alternative to IVIG for patients with PID in Spain., Open Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature. This study was funded by Shire, a Takeda company.

Objectives: Lately, many countries have restricted or even banned transfat, and palm oil has become a preferred replacement for food manufacturers. Whether palm oil is potentially an unhealthy food mainly due to its high content of saturated Palmitic Acid (PA) is a matter of debate. The aim of this study was to test whether qualitative aspects of diet such as levels of PA and the fat source are risk factors for Metabolic Syndrome (MS) and Metabolic Associated Fatty Liver Disease (MAFLD). Methods: C57BL/6 male mice were fed for 14 weeks with three types of Western diet (WD): 1. LP-WD—low concentration of PA (main fat source—corn and soybean oils), 2. HP-WD—high concentration of PA (main fat source—palm oil), 3. HP-Trans-WD—high concentration of PA (mainly transfat). Results: All types of WD caused weight gain, adipocyte enlargement, hepatomegaly, lipid metabolism alterations, and steatohepatitis. Feeding with HP diets led to more prominent obesity, hypercholesterolemia, stronger hepatic injury, and fibrosis. Only the feeding with HP-Trans-WD resulted in glucose intolerance and elevation of serum transaminases. Brief withdrawal of WDs reversed MS and signs of MAFLD. However, mild hepatic inflammation was still detectable in HP groups. Conclusions: HP and HP-Trans-WD play a crucial role in the genesis of MS and MAFLD.

12 páginas, 2 figuras, 1 tabla., A successful Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) variant, B.1.1.7, has recently been reported in the UK, causing global alarm. Most likely, the new variant emerged in a persistently infected patient, justifying a special focus on these cases. Our aim in this study was to explore certain clinical profiles involving severe immunosuppression that may help explain the prolonged persistence of viable viruses. We present three severely immunosuppressed cases (A, B, and C) with a history of lymphoma and prolonged SARS-CoV-2 shedding (2, 4, and 6 months), two of whom finally died. Whole-genome sequencing of 9 and 10 specimens from Cases A and B revealed extensive within-patient acquisition of diversity, 12 and 28 new single nucleotide polymorphisms, respectively, which suggests ongoing SARS-CoV-2 replication. This diversity was not observed for Case C after analysing 5 sequential nasopharyngeal specimens and one plasma specimen, and was only observed in one bronchoaspirate specimen, although viral viability was still considered based on constant low Ct values throughout the disease and recovery of the virus in cell cultures. The acquired viral diversity in Cases A and B followed different dynamics. For Case A, new single nucleotide polymorphisms were quickly fixed (13-15 days) after emerging as minority variants, while for Case B, higher diversity was observed at a slower emergence: fixation pace (1-2 months). Slower SARS-CoV-2 evolutionary pace was observed for Case A following the administration of hyperimmune plasma. This work adds knowledge on SARS-CoV-2 prolonged shedding in severely immunocompromised patients and demonstrates viral viability, noteworthy acquired intra-patient diversity, and different SARS-CoV-2 evolutionary dynamics in persistent cases., This research was funded by Instituto de Salud Carlos III (Ref COV20/00140: SeqCOVID—Consorcio para la epidemiología genómica de SARS-CoV-2 en España) and by Consejo Superior de Investigaciones Científicas (CSIC) (PTI Salud Global). Miguel Servet Contracts CP15/00075 and CPII20/00001) to L.P.-L.

To control the Human Immunodeficiency Virus (HIV) pandemic, the World Health Organization (WHO) set the 90-90-90 target to be reached by 2020. One major threat to those goals is late presentation, which is defined as an individual presenting a TCD4+ count lower than 350 cells/mm3 or an AIDS-defining event. The present study aims to identify determinants of late presentation in Europe based on the EuResist database with HIV-1 infected patients followed-up between 1981 and 2019. Our study includes clinical and socio-demographic information from 89851 HIV-1 infected patients. Statistical analysis was performed using RStudio and SPSS and a Bayesian network was constructed with the WEKA software to analyze the association between all variables. Among 89851 HIV-1 infected patients included in the analysis, the median age was 33 (IQR: 27.0–41.0) years and 74.4% were males. Of those, 28889 patients (50.4%) were late presenters. Older patients (&gt, 56), heterosexuals, patients originated from Africa and patients presenting with log VL &gt, 4.1 had a higher probability of being late presenters (p &lt, 0.001). Bayesian networks indicated VL, mode of transmission, age and recentness of infection as variables that were directly associated with LP. This study highlights the major determinants associated with late presentation in Europe. This study helps to direct prevention measures for this population.

Antibiotic resistance in Streptococcus pneumoniae has increased worldwide, making fluoroquinolones an alternative therapeutic option. Fluoroquinolones inhibit the type II DNA topoisomerases (topoisomerase IV and gyrase). In this study we have evaluated the in vivo activity of seconeolitsine, an inhibitor of topoisomerase I. Levofloxacin (12.5 to 50 mg/kg) or seconeolitsine (5 to 40 mg/kg) were administered every 12 h during two days in mice infected with a serotype 8-resistant strain. At 48 h, a 70% protection was obtained with seconeolitsine (40 mg/kg, p &lt, 0.001). However, survival with levofloxacin was 20%, regardless of the dose. In addition, seconeolitsine decreased bacteremia efficiently. Levofloxacin had higher levels in serum than seconeolitsine (Cmax of 14.7 vs. 1.6, 0.01) and higher values of area under the serum concentration-time curve (AUC0-12h of 17.3 vs. 5, 0.01). However, seconeolitsine showed higher levels of time to peak concentration and elimination half-life. This is consistent with the higher binding of seconeolitsine to plasma proteins (40% and 80% when used at 1 µg/mL and 50 µg/mL, respectively) in comparison to levofloxacin (12% at 5 µg/mL and 33% at 50 µg/mL). Our results suggest that seconeolitsine would be a promising therapeutic alternative against pneumococcal isolates with high fluoroquinolone resistance levels.

Introduction Despite sensitization of medical students toward the donation of organs, a non-negligible percentage of students are not in favor of donation. Objective To analyze the reasons of Spanish medical students who do not have a favorable attitude toward the donation of their own organs after death. Method The population under study is medical students in Spanish universities, using the database of the International Donor Collaborative Project, stratified by geographic area and academic year. The questionnaire completion was anonymous and self-administered. The study group is medical students with an unfavorable attitude toward organ donation. The assessment instrument used is a validated questionnaire of attitude toward the donation of organs for transplant, “PCID-DTO-Ríos.” The reasons against the donation are valued in the questionnaire through a question. Results Of the participants included in the PCID, students who are not in favor of organ donation were selected (n = 1899). Of them, 8.1% (n = 154) are against and 91.1% (n = 1745) are doubtful. The main reasons indicated are the fear of apparent death in 11.4% of respondents, fear of possible mutilation after donation in 11.1%, and religious reasons in 2.6%. Of those, 6.9% indicate other reasons but do not clearly specify the reasons, using words such as “fear” (2.5%) or “doubts about the process” (4.1%); 66.2% (n = 1257) indicated an “assertive refusal” (“I don't want to express my reasons”). Conclusion Twenty percent of Spanish medical students are not in favor of donating their organs and are not in favor of showing their reasons. Sin financiación 1.066 JCR (2020) Q4, 160/162 Inmunology 0.373 SJR (2020) Q3, 260/456 Surgery No data IDR 2020 UEM

The amniotic fluid provides mechanical protection and immune defense against pathogens to the fetus. Indeed, components of the innate and adaptive immunity, including B cells, have been described in the amniotic fluid. However, limited information concerning phenotype and functionality of amniotic fluid B cells is available. Hence, we aimed to perform a full phenotypical and functional characterization of amniotic fluid B cells in normal pregnancy and in a mouse model of preterm birth. Phenotypic analysis depicted the presence of two populations of amniotic fluid B cells: an immature population, resembling B1 progenitor cells and a more mature population. Further isolation and in vitro co-culture with a bone marrow stroma cell line demonstrated the capacity of the immature B cells to mature. This was further supported by spontaneous production of IgM, a feature of the B1 B cell sub-population. An additional in vitro stimulation with lipopolysaccharide induced the activation of amniotic fluid B cells as well as the production of pro and anti-inflammatory cytokines. Furthermore, amniotic fluid B cells were expanded in the acute phase of LPS-induced preterm birth. Overall our data add new insight not only on the phenotype and developmental stage of the amniotic fluid B1 B cells but especially on their functionality. This provides important information for a better understanding of their role within the amniotic fluid as immunological protective barrier, especially with regard to intraamniotic infection and preterm birth. Fil: Bommer, Imke. ERNST MORITZ ARNDT UNIVERSITÄT GREIFSWALD (UG); Fil: Juriol, Lorena Vanesa. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; Argentina Fil: Muzzio, Damián Oscar. ERNST MORITZ ARNDT UNIVERSITÄT GREIFSWALD (UG); Fil: Valeff, Natalin Jimena. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; Argentina Fil: Ehrhardt, Jens. ERNST MORITZ ARNDT UNIVERSITÄT GREIFSWALD (UG); Fil: Matzner, Franziska. ERNST MORITZ ARNDT UNIVERSITÄT GREIFSWALD (UG); Fil: Ziegler, Katharina. ERNST MORITZ ARNDT UNIVERSITÄT GREIFSWALD (UG); Fil: Malinowsky, Kristin. ERNST MORITZ ARNDT UNIVERSITÄT GREIFSWALD (UG); Fil: Ventimiglia, Maria Silvia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; Argentina Fil: Zygmunt, Marek. ERNST MORITZ ARNDT UNIVERSITÄT GREIFSWALD (UG); Fil: Jensen, Cristian Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; Argentina. Universidad Nacional Arturo Jauretche; Argentina

Although it is known that gestation could influence the clinical course of ovine toxoplasmosis, the precise effect of the term of gestation when sheep are infected are yet mostly unknown. The aim of this study was to evaluate the peripheral and placental immune responses developed in pregnant sheep after experimental infection with Toxoplasma gondii at different times of gestation. Thirty-six pregnant sheep were allocated in different groups, orally inoculated with sporulated oocysts of T. gondii at early, mid and late gestation and culled within 30 days post-infection. The peripheral humoral and cytokine responses were evaluated, as well as the transcription of cytokines at the placenta. Serological analysis revealed that, regardless the term of gestation when infected, specific IgG against T. gondii were detected from day 8 post-infection and there was an early peripheral release of IFN-γ at the first week post-infection followed by a short peak of IL10 and TNF-α at the second week post-infection. There were no significant differences in this response between infected groups. At the placenta, a similar increase in transcription of IFN-γ, and TNF-α was found at the three terms of gestation, while IL-4 increased mainly at the first and second terms and IL-10 transcription was higher at the last term. While these findings show that both Th1 and Th2 cytokines play a key role in the pathogenesis of ovine toxoplasmosis and that placental and peripheral immune responses do not closely correlate, there seems to be no clear modulation of these responses along the gestation., The authors wish also to thank to Dr Frank Katzer, from Moredun Research Institute for kindly providing the tachyzoites from M4 isolate, all the staff of the IGM (CSIC-ULE) responsible for handling the experimental animals, and the technical assistance of Mr. Panero, Mrs. Espiniella, Mrs. González and Mrs. Agudín. P. Castaño is founded by a predoctoral contract from the “Junta de Castilla y León”. We acknowledge support of the publication fee by the CSIC Open Access Publication Support Initiative through its Unit of Information Resources for Research (URICI). This work was supported by Grants AGL2011-30205 and AGL2016-75935-C2-2-R and of the Spanish Ministry of Science and Innovation, and LE253U13, from the Junta de Castilla y León, Spain.

Breast cancer is one of the leading causes of death worldwide. It is recognised that immune system influences its promotion, progression, and metastasis, as well as their responsiveness to therapies. Previously, it was reported that milk fermented by Lactobacillus casei CRL431 decreased tumour growth and metastasis in a mouse breast cancer model, through the modulation of the host immune response. The aim of the present work was to analyse the systemic immune response induced by the administration of probiotic fermented milk (PFM) at different stages of cancer development, evaluating cytokines produced by splenocytes stimulated in vitro with 4T1 tumour cells, or its conditioned medium (CM). Groups of healthy mice and mice bearing 4T1 tumour or suffering metastasis after tumour surgery were studied. Results showed that at the early stages, PFM maintained pro-inflammatory response associated to the delay or the inhibition of tumour growth. PFM administration to mice bearing tumour maintained an important inflammatory response; however, in contrast to the milk group, this response was regulated to avoid exacerbation of inflammation. In the metastasis model, the benefits of PFM were associated to avoid the immunosuppression associated to high interleukin-10 levels. In conclusion, as cancer cells induce modifications of the immune response to favour their own growth at each stage of cancer development, PFM administration stimulated different profile of cytokines to respond to these modifications and fight against cancer cells. Fil: Méndez Utz, Virginia Emilce. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina Fil: Perdigon, Gabriela del Valle. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina Fil: de Moreno, Maria Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina

Resumen El propósito de esta revisión es resaltar la importancia de la investigación en el área de la inmunología y su aplicación en el ámbito clínico. En una primera parte se presentan los descubrimientos más importantes que ayudaron a dilucidar los principales procesos fisiológicos involucrados en las enfermedades y de esta manera ayudaron a redireccionar la investigación en el área de la inmunología. Seguido, se describe un ejemplo de investigación básica relacionada con el papel de las citocinas en el absceso hepático amebiano, mostrando el trabajo de varios grupos de investigación en el mundo, con el objetivo de entender la respuesta inmune contra el parásito. Lo anterior nos permite argumentar la relevancia que tiene la investigación inmunológica dentro del contexto clínico. Abstract The purpose of this review is to highlight the importance of research in immunology and its application in the clinical setting. The first part presents the most important discoveries that helped to elucidate the main physiological processes involved in the diseases and in this way helped to redirect research in immunology. Then, we describe an example of basic research related to the role of cytokines in the amoebic liver abscess, showing the work of several research groups in the world, with the aim of understanding the immune response against the parasite. This allows us to argue the relevance of immunological research within the clinical context.

According to the oxidative-inflammatory theory of aging, there is a link between the function, the oxidative-inflammatory stress state of immune cells, and longevity. However, it is unknown which immune cell parameters can predict lifespan and if there would be any changes in this prediction, depending on the age of the subject. Therefore, a longitudinal study in mice was performed analysing immune function (chemotaxis of macrophages and lymphocytes, phagocytosis of macrophages, natural killer (NK) activity, and lymphoproliferation capacity), antioxidant (catalase (CAT), glutathione peroxidase (GPx), and glutathione reductase (GR) activities as well as reduced glutathione (GSH) concentrations), oxidant (oxidized glutathione (GSSG), superoxide anion, and malondialdehyde (MDA) concentrations), and inflammation-related markers (basal release of IL-1β, IL-6, TNF-α, and IL-10) in peritoneal leukocytes from mice at the adult, mature, old, very old, and long-lived ages (40, 56, 72, 96, and 120±4 weeks of age, respectively). The results reveal that some of the investigated parameters are determinants of longevity at the adult age (lymphoproliferative capacity, lymphocyte chemotaxis, macrophage chemotaxis and phagocytosis, GPx activity, and GSH, MDA, IL-6, TNF-α, and IL-10 concentrations), and therefore, they could be proposed as markers of the rate of aging. However, other parameters are predictive of extreme longevity only at the very old age (NK activity, CAT and GR activities, and IL-6 and IL-1β concentrations), and as such, they could reflect some of the adaptive mechanisms underlying the achievement of high longevity. Nevertheless, although preliminary, the results of the present study provide a new perspective on the use of function, redox, and inflammatory parameters in immune cells as prognostic tools in aging research and represent a novel benchmark for future work aimed at prediction of lifespan.

Several reports show deficiencies in the knowledge of physicians about the diagnostic criteria and the treatment of anaphylaxis, a condition that can have fatal consequences.To evaluate the knowledge of physicians in Colombia on the fundamental aspects of anaphylaxis in diagnosis and treatment.Analytical cross-sectional study, carried out through a survey of 11 questions that evaluate clinical aspects of anaphylaxis, addressed to general practitioners and specialists in different health areas resident in Colombia. The analysis of the results was based on the correct answers. For approval, a score higher than 70% was needed.A total of 447 non-allergic doctors analyzed were included, of which only 110 (24.6%) approved the questionnaire in both the questions aimed at the diagnosis and in the treatment of anaphylaxis. Among the factors that were associated with the failure of the survey were the age of the doctor (p0.01) and work at the first level of care (p0.01).Like previous studies, knowledge in the diagnosis and treatment of anaphylaxis is scarce among Colombian physicians. The factors associated with said result are potentially modifiable.Antecedentes: Varios reportes evidencian la necesidad de mayor conocimiento de los médicos acerca de los criterios diagnósticos y de manejo de la anafilaxia, condición que puede tener consecuencias fatales. Objetivo: Evaluar en Colombia los conocimientos de los médicos no alergólogos, acerca de los aspectos fundamentales de la anafilaxia en el diagnóstico oportuno y el tratamiento. Métodos: Estudio transversal realizado mediante una encuesta de 11 preguntas relativas a aspectos clínicos de la anafilaxia, dirigida a médicos generales y especialistas residentes en Colombia. El análisis de los resultados se hizo con base en las respuestas correctas. El corte de aprobación se estableció en70 %. Resultados: Se incluyeron 447 médicos no alergólogos, de los cuales solo 110 (24.6 %) aprobaron el cuestionario tanto en los aspectos diagnóstico como terapéuticos. Entre los factores asociados con reprobar la encuesta se identificó mayor edad (p0.01) y trabajar en el primer nivel de atención (p0.01). Conclusiones: Similar a lo reportado en otros estudios, el conocimiento en el diagnóstico y tratamiento de la anafilaxia fue deficiente entre los médicos colombianos. Los factores asociados con estos resultados son potencialmente modificables.