The autoimmune ecology: An update

Purpose of review The autoimmune ecology refers to the interactions between individuals and their environment leading to a breakdown in immune tolerance and, therefore, to the development of one or more autoimmune diseases in such an individual. Herein, an update is offered on four specific factors associated with autoimmune diseases, namely, Vitamin D, smoking, alcohol and coffee consumption from the perspective of exposome and metabolomics. Recent findings Smoking is associated with an increased risk for most of the autoimmune diseases. Carbamylation of proteins as well as NETosis have emerged as possible new pathophysiological mechanisms for rheumatoid arthritis. Low-to-moderate alcohol consumption seems to decrease the risk of systemic lupus erythematosus and rheumatoid arthritis, and studies of vitamin have suggested a beneficial effect on these conditions. Coffee intake appears to be a risk factor for type 1 diabetes mellitus and rheumatoid arthritis and a protective factor for multiple sclerosis and primary biliary cholangitis. Summary Recent studies support the previously established positive associations between environmental factors and most of the autoimmune diseases. Nevertheless, further studies from the perspective of metabolomics, proteomics and genomics will help to clarify the effect of environment on autoimmune diseases. © Copyright 2018 Wolters Kluwer Health, Inc. All rights reserved

Potenciación de la respuesta inmune humoral sistémica en ratas lactantes por el ácido linoleico conjugado (CLA)

Cis-9, trans-11 (c9, t11) and trans-10, cis-12 (t10, c12) are the predominating molecules in the positional and geometrical isomers mixture termed CLA. Although CLA has shown positive effects on human health and seems to be associated with immunomodulatory activities, its effect in the developing immune system has not been studied. Thus, the present study was designed to establish the effect of CLA supplementation during gestation and/or lactation on humoral immune response, i.e. by analysing sera Ig levels during the suckling period. Wistar rats were allocated to four groups (A, B, C and W) on day 7 of pregnancy. From day 7 and throughout the study period group C and W gestating mothers were fed standard pellet chow. Group A and B dams were fed 10 g CLA (80% cis-9, trans-11, 20% trans-10, cis-12; Lipid Nutrition B. V. Wormerveer, The Netherlands)/kg pellet chow during gestation. Moreover, group A mothers were also fed the CLA-supplemented chow until the litters were 21 d old, the end of suckling period. Group B and C litters received the CLA mixture of isomers by daily oral administration while their respective dams were fed standard pellet chow during lactation. In all cases litters were equalised to ten rats per lactating mother. Pups from each experimental group were killed at the end of the second week of life (day 14) and at the end of the suckling period (day 21), and blood samples were collected. Serum IgA, IgG and IgM levels were quantified by the ELISA sandwich technique. ANOVA and post hoc comparisons (LSD test) were performed. Differences were considered to be significant at P<0.05. Animals receiving CLA passively from their mothers (group A) during gestation and the suckling period exhibited the highest concentrations of IgG and IgM at 14 d old (P<0.05; see Table). At the end of suckling period the serum IgG concentration in this group was also increased, up to three times more than in the other groups (P<0.05). Those animals supplemented with CLA only during suckling period (group C) showed no difference in relation to those receiving no supplement. Thus, these results demonstrate that CLA supplementation during gestation and lactation promotes systemic humoral immune response

Autoimmune neurological conditions associated with Zika virus infection

Zika virus (ZIKV) is an emerging flavivirus rapidly spreading throughout the tropical Americas. mosquitoes is the principal way of transmission of the virus to humans. ZIKV can be spread by transplacental, perinatal, and body fluids. ZIKV infection is often asymptomatic and those with symptoms present minor illness after 3 to 12 days of incubation, characterized by a mild and self-limiting disease with low-grade fever, conjunctivitis, widespread pruritic maculopapular rash, arthralgia and myalgia. ZIKV has been linked to a number of central and peripheral nervous system injuries such as Guillain-Barré syndrome (GBS), transverse myelitis (TM), meningoencephalitis, ophthalmological manifestations, and other neurological complications. Nevertheless, mechanisms of host-pathogen neuro-immune interactions remain incompletely elucidated. This review provides a critical discussion about the possible mechanisms underlying the development of autoimmune neurological conditions associated with Zika virus infection

The autoimmune ecology

Autoimmune diseases (ADs) represent a heterogeneous group of disorders that affect specific target organs or multiple organ systems. These conditions share common immunopathogenic mechanisms (i.e., the autoimmune tautology), which explain the clinical similarities they have among them as well as their familial clustering (i.e., coaggregation). As part of the autoimmune tautology, the influence of environmental exposure on the risk of developing ADs is paramount (i.e., the autoimmune ecology). In fact, environment, more than genetics, shapes immune system. Autoimmune ecology is akin to exposome, that is all the exposures - internal and external - across the lifespan, interacting with hereditary factors (both genetics and epigenetics) to favor or protect against autoimmunity and its outcomes. Herein, we provide an overview of the autoimmune ecology, focusing on the immune response to environmental agents in general, and microbiota, cigarette smoking, alcohol and coffee consumption, socioeconomic status (SES), gender and sex hormones, vitamin D, organic solvents, and vaccines in particular. Inclusion of the autoimmune ecology in disease etiology and health will improve the way personalized medicine is currently conceived and applied. © 2016 Anaya, Ramirez-Santana, Alzate, Molano-Gonzalez and Rojas-Villarraga

La proteína 78 regulada por glucosa (GRP78) interactúa con la envoltura del virus del Zika y es necesaria para una infección productiva

Zika virus (ZIKV) is a member of the Flaviviridae family and was until recently a relatively obscure tropical disease. Subsequently, ZIKV has been shown to be the causative agent of fetal abnormalities and Guillain-Barré syndrome in outbreaks across the Americas and so efforts towards delineating important factors in the viral lifecycle have increased. Combining protein pull-down with mass spectrometry, it was found that ZIKV envelope (Env) interacts with the endoplasmic reticulum (ER) resident chaperone, glucose regulated protein 78 (GRP78) in A549 cells. Flaviviruses such as Japanese encephalitis virus and dengue virus are known to co-opt ER resident proteins and members of the unfolded protein response, including GRP78, to enhance viral infectivity and propagation. The role these proteins play during the ZIKV lifecycle has yet to be elucidated. To determine the importance of this interaction during ZIKV infection, A549 cells were treated with GRP78-specific siRNAs prior to infection with a NanoLuc expressing reporter virus or a wild-type virus. Depletion of GRP78 significantly reduced both virus luciferase readings and viral titres, indicating that GRP78 is necessary for efficient infection of mammalian cell culture. In contrast, inhibition of GRP78 with small molecule inhibitors did not reduce ZIKV infection. Interestingly, immunofluorescence of ZIKV infected cells reveal that GRP78 re-localises following infection and co-localises with Env. Depletion of GRP78 abrogated localisation of viral replication factories. Further experiments have shown that GRP78 is important for infection post entry and replication, and that putative GRP78 interactions partners are also required during infection

Mayor producción de inmunoglobulina en ratas suplementadas con ácido linoleico conjugado durante la gestación y la lactancia

Conjugated linoleic acid (CLA) has been reported to exert beneficial physiological effects on body composition and the immune system. However, little information is available on the influence of CLA on immune function during early life periods. The present study evaluates the effect of feeding an 80:20 mixture of cis-9, trans-11- and trans-10, cis-12-CLA isomers during gestation and suckling on the systemic immune response of weaned Wistar rats. Pups received dietary CLA from dams through the placental barrier and during suckling by breast milk (group A) or by oral administration (group B). Pups from group C only received CLA during suckling by oral administration. Group D constituted the reference group. Milk from dams fed the CLA diet had a high content of CLA and higher IgA and IgG concentrations than rats fed the standard diet. The plasma of pups from groups A, B and C showed six, twelve and nine times higher content of the cis-9, trans-11-CLA isomer than that of the group D pups. Rats from group A exhibited higher serum IgG concentrations than rats from the rest of the groups (22·14 (sem 2·14) v. about 5 mg/ml; P < 0·05), whereas rats from groups A and B showed approximately 2-fold higher splenocyte IgM production than rats from groups C and D. However, CLA supplementation did not influence significantly the splenocyte proliferative response or cytokine secretion. Supplementation during gestation and suckling with an 80:20 cis-9, trans-11–trans-10, cis-12 CLA mix enhances the production of the main in vivo and in vitro Ig isotypes in Wistar rats

Endothelial Damage in Sepsis: The Importance of Systems Biology

The early diagnosis and appropriate stratification of sepsis continues to be one of the most important challenges in modern medicine. Single isolated biomarkers have not been enough to improve diagnostic and prognostic strategies and to progress toward therapeutic goals. The information generated by the human genome project has allowed a more holistic approach to the problem. The integration of genomics, transcriptomics, proteomics and metabolomics in sepsis has allowed us to progress in the knowledge of new pathways which are pathophysiologically involved in this disease. Thus, we have understood the importance of and complex interaction between the inflammatory response and the endothelium. Understanding the role of important parts of the microcirculation, such as the endothelial glycocalyx and its interaction with the inflammatory response, has provided early recognition elements for clinical practice that allow the rational use of traditional medical interventions in sepsis. This comprehensive approach, which differs from the classical mechanistic approach, uses systems biology to increase the diagnostic and prognostic spectrum of endothelial damage biomarkers in sepsis, and to provide information on new pathways involved in the pathophysiology of the disease. This, in turn, provides tools for perfecting traditional medical interventions, using them at the appropriate times according to the disease's pathophysiological context, while at the same time discovering new and improved therapeutic alternatives. We have the challenge of transferring this ideal scenario to our daily clinical practice to improve our patients' care. The purpose of this article is to provide a general description of the importance of systems biology in integrating the complex interaction between the endothelium and the inflammatory response in sepsis

Comportamiento clínico y epidemiológico de la enfermedad trofoblástica gestacional en pacientes ingresadas en el servicio de complicaciones obstétricas del Hospital Berta calderón Roque durante el año 2017 – 2019

El objetivo de este estudio es describir el comportamiento clínico y epidemiológico de la enfermedad trofoblástica gestacional en pacientes atendidas en el servicio de complicaciones obstétricas del Hospital Berta calderón Roque durante el año 2017-2019. Se realizó un estudio, Descriptivo, de corte transversal, informe de Casos revisando 9 expedientes clínicos de pacientes con enfermedad trofoblástica. La edad que mayormente afecta a la población fue de 21 años en el 33,3% de los casos, el intervalo fue el comprendido entre los 20 – 34 años en un 66,7%. Escolaridad en el 66, 7 % de primaria. El 88,9 % era ama de casa El 44,4 % se encontraba en unión libre. Los antecedentes gineco- obstétricos fueron: Bigestas en 55,6%, entre las 12- 24 semanas de gestación en el 88,9%, El 100% de las mujeres no presento como antecedente aborto molar. El 100% fue diagnosticada durante el primer control prenatal. El 88,9 % no presento como antecedente aborto. El 77,8% era multípara. El 100% de la población presento embarazo molar, de los cuales el 55,6% presento mola hidatiforme parcial. La principal manifestación clínica fue el en el 88,9% sangrado transvaginal. El 100% de las pacientes se diagnosticó mediante ultrasonido Pélvico y tuvo diagnóstico histopatológico confirmado por biopsia. La mayoría no presento complicaciones y evoluciono de manera satisfactori

Effects of a cocoa diet on an intestinal inflammation model in rats

Cocoa is a rich source of fiber and flavonoids with recognized antioxidant and anti-inflammatory potential. The aim of this study was to evaluate the effects of a cocoa-enriched diet on rats with dextran sulphate sodium (DSS)-induced colitis. Wistar rats were fed with either a 5% cocoa diet or standard diet. Colon inflammation was induced by DSS in the drinking water: 5% for 6 days and 2% over the following 9 days. Colitis was assessed by body weight loss, stool consistency and blood presence in stools. A group of animals fed standard diet was treated with quercitrin (1 mg/kg) after colitis establishment. After 2 weeks of DSS treatment, the colon oxidative and inflammatory status and lymphocyte composition from blood and mesenteric lymph nodes (MLN) were assessed. The cocoa-fed group did not exhibit amelioration of clinical colitis but displayed higher antioxidant activity than the colitic reference group by the restoration of colon glutathione content and prevention of lipid peroxidation. The cocoa diet showed anti-inflammatory potential because it down-regulated serum TNF-alpha, colon iNOS activity and decreased colon cell infiltration. Lymphocyte composition in MLN was not modified by drinking DSS, but there was an increase in the proportion of NK and regulatory T cells in the blood. These changes were not modified by cocoa. In conclusion, cocoa intake may help to inhibit the negative oxidative effects consequent to colitis, although this action is not enough to abrogate the intestinal inflammation significantly

Glucose-Regulated Protein 78 Interacts with Zika Virus Envelope Protein and Contributes to a Productive Infection.

Zika virus (ZIKV; Flaviviridae) is a mosquito-borne flavivirus shown to cause fetal abnormalities collectively known as congenital Zika syndrome and Guillain-Barre syndrome in recent outbreaks. Currently, there is no specific treatment or vaccine available, and more effort is needed to identify cellular factors in the viral life cycle. Here, we investigated interactors of ZIKV envelope (E) protein by combining protein pull-down with mass spectrometry. We found that E interacts with the endoplasmic reticulum (ER) resident chaperone, glucose regulated protein 78 (GRP78). Although other flaviviruses are known to co-opt ER resident proteins, including GRP78, to enhance viral infectivity, the role ER proteins play during the ZIKV life cycle is yet to be elucidated. We showed that GRP78 levels increased during ZIKV infection and localised to sites coincident with ZIKV E staining. Depletion of GRP78 using specific siRNAs significantly reduced reporter-virus luciferase readings, viral protein synthesis, and viral titres. Additionally, GRP78 depletion reduced the ability of ZIKV to disrupt host cell translation and altered the localisation of viral replication factories, though there was no effect on viral RNA synthesis. In summary, we showed GRP78 is a vital host-factor during ZIKV infection, which may be involved in the coordination of viral replication factories