Anti-carbamylated protein and peptide antibodies as potential inflammatory joint biomarkers in the relatives of rheumatoid arthritis patients

*Q3Objective: Antibodies against carbamylated proteins/peptide (CarP) have been associated with severity in rheumatoid arthritis (RA) patients. However, their role in risk groups, specific targets and relation with periodontal disease (PD) is uncertain yet. The aim of this study was evaluated the association between the levels of anti- CarP with clinical manifestation, human leukocyte antigen (HLA) alleles, periodontal activity markers, PD diagnosis, PD severity, and presence of Porphyromonas gingivalis (P gingivalis) in relatives of patients with RA. Methods: One hundred and twenty-four individuals with a family history of RA in first-degree relatives (FDR) and 124 healthy individuals gender- and age-matched, RA activity was assessed. Antibodies against carbamylated protein anti-FCS-Carp and 2 carbamylated peptides of fibrinogen were selected (anti-Ca-Fib2, anti-Ca-Fib3). Results: Anti-FCS-Carp-positive, anti-Ca-Fib2 and anti-Ca-Fib3 were more frequent in FDR than controls (25.0% vs 14.5%, 34.7% vs 15.3% and 33.1% vs 11.3%, respectively). Anti-FCS-CarP were associated with the HLA-DRB1-SE* 1402 allele (P = .035) and highly sensitive C-reactive protein levels (P = .016), the anti-Ca-Fib2 antibodies were associated with the HLA-DRB1-SE* 1501 allele (P = .03), with non-SE* 0901 allele (P = .01), the anti-Ca-Fib3 was associated with positive rheumatoid factor (P = .0012). The FDR condition was associated with the presence of anti-Ca-Fib3 (odds ratio [OR] =4.7; 95% CI = 1.8-11.7; P = .001) and painful joints (OR = 2.2; 95% CI = 1.01-4.68; P = .045); we also detected an important trend toward the presence of P gingivalis (OR = 1.9; 95% CI = 0.9-3.7; P = .062). Conclusion: The presence of anti-FCS-Carp, anti-Ca-Fib3 and anti-Ca-Fib2 antibodies may have a role for these antibodies as early biomarkers in the development of RA, probably including additional mechanisms related with other non-SE alleles; the anti-peptide antibodies proposed in the present study may represent a simpler way to identify antibodies directed to a specific target.N/

Comparison of plasma cytokine levels before and after treatment with rituximab in patients with rheumatoid arthritis and systemic lupus erythematosus-associated polyautoimmunity

Introducción: La coexistencia de más de una enfermedad autoinmune (EAI) en un paciente se conoce como poliautoinmunidad (PAI) y se observa en el 35% de los pacientes con EAI. La eliminación de linfocitos B usando rituximab (RTX) controla la actividad de diferentes EAI. En el lupus eritematoso sistémico (LES) y en PAI no es clara la producción de citocinas por los linfocitos B. Métodos: Estudio exploratorio. Se obtuvo plasma de 11 pacientes con artritis reumatoide (AR) y poliautoinmunidad asociada a LES (PAILES) antes y después de rituximab (i. e., 6 meses). Como controles se utilizaron ocho individuos sanos. Las citocinas se midieron por ELISA (IFN-α, TGF-β1) o Cytometric Bead Array (TNF-α, IL-1β, IL-6, IL-8, IL-10, IL-12p70). Resultados: Previo a RTX, IL-6 se encontró elevada únicamente en AR, mientras que IL-8 lo estuvo en AR y en PAILES, comparados con controles. Después de RTX se encontró una disminución significativa de IL-6 en AR y de IL-8 en PAILES. Las concentraciones de otras citocinas medidas fueron similares (IFN-α, TGF-β1) o se encontraron por debajo de límite de detección (TNF-α, IL-1β, IL-10, IL-12p70), tanto en pacientes como en controles. Conclusión: Los datos resaltan la importancia de la secreción de citocinas por los linfocitos B y sugieren un rol diferencial en cada patología. El incremento de IL-8 previo a RTX en ambos grupos y la reducción después de la terapia en PAILES respaldan el potencial de la IL-8 como objetivo terapéutico. La heterogeneidad de la población de pacientes con PAI reafirma la importancia de la selección de subgrupos específicos en estudios futuros.Artículo original21-36Introduction: Coexistence of more than one autoimmune disease (AD) in a single patient is known as polyautoimmunity, and may be seen in up to 35% of patients with ADs. The elimination of B'cells using Rituximab (RTX) improves clinical status in different ADs. The role of cytokine production by B'cells is unclear in systemic lupus erythematosus (SLE) and polyautoimmunity. Methods: As an exploratory study, plasma from 11 patients with either rheumatoid arthritis (RA) or SLE-associated polyautoimmunity was assessed prior and 6 months after therapy with RTX. Eight healthy individuals were used as controls. Cytokine levels were measured using ELISA (IFN-α and TGF-β1) or Cytometric Bead Array (TNF-α, IL-1β, IL-6, IL-8, IL-10, and IL-12p70). Results: Prior to RTX, IL-6 was only elevated in RA and IL-8 was elevated in both RA and SLE-associated polyautoimmunity, compared with controls. After RTX, significant decreases of IL-6 in RA and IL-8 in SLE'associated polyautoimmunity were observed. Levels of other cytokines measured were either similar (IFN-α, TGF-β1) or below the detection limit (TNF-α. IL-1β. IL-10, IL-12p70) for both patients and controls. Conclusion: Our data highlight the importance of B'cell cytokine secretion in RA and SLE'associated polyautoimmunity, and suggest a differential role in each pathology. A significant increase of IL-8 prior to RTX in both groups, and a significant decrease after therapy only in SLE'associated polyautoimmunity support the potential of IL'8 as a therapeutic target. The heterogeneity of the polyautoimmunity patient population highlights the importance of the selection of specific subsets in future research

Effect of Rituximab on the circulating levels of cytokines produced or not produced by B lymphocytes in patients with rheumatoid arthritis

Rheumatoid Arthritis (RA) is a common autoimmune disease characterized by chronic inflammation in the joints that can progress to bone destruction. Although the pathophysiology of RA is unclear, T cells and B cells are though to be involved. Rituximab (RTX), a drug that eliminates CD20 + B cells, has helped to clarify and highlight the role of B cells in RA. B cells can contribute to autoimmunity by mechanisms dependent on the production of antibodies and independent of this production. The latter may depend on the role of B cells as antigen-presenting cells for T cells and their capacity to produce cytokines and chemokines. To contribute to our understanding of this mechanism, studies that evaluated levels of circulating cytokines and chemokines in patients with RA after treatment with RTX were reviewed. Most cytokines studied decreased their levels in circulation after treatment with RTX. IL-10 and IL-6 consistently were decreased in patients responding to treatment and maybe markers of Rituximab treatment

High plasma levels of soluble ST2 but not its ligand IL-33 is associated with severe forms of pediatric dengue

Q2Q1766-771Identification of early determinants of dengue disease progression, which could potentially enable individualized patient care are needed at present times. Soluble ST2 (sST2) has been recently reported to be elevated in the serum of children older than 2 years old and adults with dengue infection and it was correlated with secondary infections as well as with severe presentations of the disease. The mechanism by which secreted ST2 is linked to severe dengue and plasma leakage remains unclear. One possibility is that IL-33 ligand may be elevated, contributing to membrane bound ST2 as part of the immune activation in dengue infection. We determined plasma levels of sST2 and the ligand IL-33 in 66 children with acute secondary dengue infections clinically classified using the guidelines of the World Health Organization, 2009. Dengue infection showed significant increases in cytokines IL-12p70, IL-10, IL-8, IL-6, IL-1β and TNFα measured by flow cytometry based assay compared to uninfected individuals. In contrast, IL-33 levels remained unchanged between infected and uninfected individuals. The levels of sST2 positively correlated with values of IL-6 and IL-8 and inversely correlated with number of median value of platelet levels. In addition to circulating cytokine positive correlations we found that sST2 and isoenzyme creatine kinase-MB (CK-MB), a marker of myocardial muscle damage present in severe dengue cases were associated. Our pediatric study concluded that in dengue infections sST2 elevation does not involve concomitant changes of IL-33 ligand. We propose a study to assess its value as a predictor factor of disease severity

Caco-2 cells infected with rotavirus release extracellular vesicles that express markers of apoptotic bodies and exosomes

Q3Q2Artículo original697-708Previously, we showed that infecting human intestinal epithelial cells (Caco-2) with rotavirus (RV) increases the release of extracellular vesicles (EVs) with an immunomodulatory function that, upon concentration at 100,000×g, present buoyant densities on a sucrose gradient of between 1.10 to 1.18 g/ml (characteristic of exosomes) and higher than 1.24 g/ml (proposed for apoptotic bodies). The effect of cellular death induced by RV on the composition of these EV is unknown. Here, we evaluated exosome (CD63, Hsc70, and AChE) and apoptotic body (histone H3) markers in EVs isolated by differential centrifugation (4000×g, 10,000×g, and 100,000×g) or filtration/ultracentrifugation (100,000×g) protocols. When we infected cells in the presence of caspase inhibitors, Hsc70 and AChE diminished in EVs obtained at 100,000×g, but not in EVs obtained at 4000×g or 10,000×g. In addition, caspase inhibitors decreased CD63 and AChE in vesicles with low and high buoyant densities. Without caspase inhibitors, RV infection increased exosome markers in all of the EVs obtained by differential centrifugation. However, CD63 preferentially localized in the 100,000×g fraction and H3 only increased in EVs concentrated at 100,000×g and with high buoyant densities on a sucrose gradient. Thus, RV infection increases the release of EVs that, upon concentration at 100,000×g, are composed by exosomes and apoptotic bodies, which can partially be separated using sucrose gradients

La vida es posible con lupus

Esta cartilla ha sido diseñada para pacientes con lupus eritematoso sistémico (LES) y para familiares de estos pacientes que quieran conocer más acerca de esta condición de vida. Fue escrita por personas que tienen contacto directo con los pacientes, o son pacientes. Esperamos que sea de gran utilidad para cada uno de los lectores como una herramienta para saber, recordar y reforzar que la vida es posible con LES, y que se puede vivir en armonía con esta realidad. A lo largo de la cartilla se podrá encontrar información pertinente y actualizada, recomendaciones, consejos y algunas propuestas de ejercicios para asumir los desafíos que se presentan en el día a día de los pacientes y sus cuidadores o familiares.Bogot

Manual de diseño curricular para el desarrollo de competencias en la formación profesional integral

Manual destinado a las áreas responsables de la formación profesional del SENA que describe el conjunto de procedimientos y actividades para el diseño de estructuras curriculares y módulos de formación con base en competencias laborales que permiten orientar los procesos pedagógicos, comprende desde la interpretación de los referentes para elaborar el diseño curricular hasta la aprobación, formalización y divulgación de los productos para su validación posterior y ajuste.Manual for the areas responsible for professional training of SENA that describes the set of procedures and activities for the design of curricular structures and training modules based on work skills that allow guiding the pedagogical processes, including from the interpretation of the references for develop the curricular design until the approval, formalization and dissemination of the products for subsequent validation and adjustment.Objetivo -- Alcance -- Definiciones -- Diagrama de flujo -- Descripción del proceso -- Revisión y actualización -- Formatos -- Referencias documentales -- Anexos -- Perfil del equipo de diseño curricular y del asesor pedagógico -- Referentes del diseño curricular -- Guía para elaboración de perfiles de entrada y salida de alumnos -- Presentación de estructuras curriculares y módulos de formación – Taxonomías de verbos -- Orientaciones para la elaboración de guías de aprendizaje -- Orientaciones para la elaboración de instrumentos de evaluación -- Orientaciones para diligenciar el formato estándares de máquinas/Equipos, herramientas y materiales de formación -- Orientaciones para la codificación de estructuras curriculares -- Orientaciones para la actualización de estructuras curriculares – Orientaciones para el diseño de programas de formación por dependenciaVersión

Immunomodulators released during rotavirus infectionof polarized caco-2 cells

Q4Q3163-172Rotavirus preferentially replicates in enterocytes and "danger signals" released by these cells are likely to modulate viral immunity. As a model of these events, we studied selected immunomodulators released during rotavirus infection of polarized Caco-2 cells grown in transwell cultures (TW). At early time points post-infection the virus was detected mainly in the apical side of the TWs, but this tendency was progressively lost concomitantly with disruption of the cell monolayer and cell death. Rotavirus-infected cells released IL-8, PGE[sub]2, small quantities of TGF-β1, and the constitutive and inducible heat shock proteins HSC70 and HSP70, but not IL-1β, IL-6, IL-10, IL-12p70, or TNF-α. This set of immunomodulators is known to induce a non-inflammatory (non-Th-1) immune response, and may be determining, in part, the relatively low T-cell immune response observed in blood samples after RV infection

Interaction of rotavirus with human peripheral blood mononuclear cells : plasmacytoid dendritic cells play a role in stimulating memory rotavirus specific T cells in vitro

Q3Q2174-184We studied the interaction of RV with human peripheral blood mononuclear cells (PBMC) from adult volunteers. After exposure of PBMC to rhesus RV (RRV), T and B lymphocytes, NK cells, monocytes, and myeloid and plasmacytoid dendritic cells expressed RV non-structural proteins, at variable levels. Expression of these RV proteins was abolished if infection was done in the presence of anti-VP7 neutralizing antibodies or 10% autologous scrum. Supernatants of RRV exposed PBMC contained TNF-a, IL-6, IFN-a, IFN-y, IL-2 and IL-10. Plasmacytoid DC were found to be the main source of IFN-a production, and in their absence the production of IFN-y and the frequency of RV specific T cells that secrete IFN-y diminished. Finally, we could not detect RV-antigen associated with the PBMC or expression of RV non-structural proteins in PBMC of acutely RV-infected children. Thus, although PBMC are susceptible to the initial steps of RV infection, most PBMC of children with RV-gastrocntcritis arc not infected

Comparación de citocinas plasmáticas antes y después del tratamiento con rituximab en pacientes con artritis reumatoide y lupus eritematoso sistémico asociado a poliautoinmunidad

Coexistence of more than one autoimmune disease (AD) in a single patient is known as polyautoimmunity, and may be seen in up to 35% of patients with ADs. The elimination of B-cells using Rituximab (RTX) improves clinical status in different ADs. The role of cytokine production by B-cells is unclear in systemic lupus erythematosus (SLE) and polyautoimmunity. Methods: As an exploratory study, plasma from 11 patients with either rheumatoid arthritis (RA) or SLE-associated polyautoimmunity was assessed prior and 6 months after therapy with RTX. Eight healthy individuals were used as controls. Cytokine levels were measured using ELISA (IFN-α and TGF-β1) or Cytometric Bead Array (TNF-α, IL-1β, IL-6, IL-8, IL-10, and IL-12p70). Results: Prior to RTX, IL-6 was only elevated in RA and IL-8 was elevated in both RA and SLE-associated polyautoimmunity, compared with controls. After RTX, significant decreases of IL-6 in RA and IL-8 in SLE-associated polyautoimmunity were observed. Levels of other cytokines measured were either similar (IFN-α, TGF β1) or below the detection limit (TNF-α, IL-1β, IL-10, IL-12p70) for both patients and controls. Conclusion:Our data highlight the importance of B-cell cytokine secretion in RA and SLE-associated polyautoimmunity, and suggest a differential role in each pathology. A significant increase of IL-8 prior to RTX in both groups, and a significant decrease after therapy only in SLE-associated polyautoimmunity support the potential of IL-8 as a therapeutic target. The heterogeneity of the polyautoimmunity patient population highlights the importance of the selection of specific subsets in future research.La coexistencia de más de una enfermedad autoinmune (EAI) en un paciente se conoce como poliautoinmunidad (PAI) y se observa en el 35% de los pacientes con EAI. La eliminación de linfocitos B usando rituximab (RTX) controla la actividad de diferentes EAI. En el lupus eritematoso sistémico (LES) y en PAI no es clara la producción de citocinas por los linfocitos B. Métodos: Estudio exploratorio. Se obtuvo plasma de 11 pacientes con artritis reumatoide (AR) y poliautoinmunidad asociada a LES (PAILES) antes y después de rituximab (i. e., 6 meses). Como controles se utilizaron ocho individuos sanos. Las citocinas se midieron por ELISA (IFN-α, TGF-β1) o Cytometric Bead Array (TNF-α, IL-1β, IL-6, IL-8, IL-10, IL-12p70). Resultados: Previo a RTX, IL-6 se encontró elevada únicamente en AR, mientras que IL-8 lo estuvo en AR y en PAILES, comparados con controles. Después de RTX se encontró una disminución significativa de IL-6 en AR y de IL-8 en PAILES. Las concentraciones de otras citocinas medidas fueron similares (IFN-α, TGF-β1) o se encontraron por debajo de límite de detección (TNF-α, IL-1β, IL-10, IL-12p70), tanto en pacientes como en controles. Conclusión: Los datos resaltan la importancia de la secreción de citocinas por los linfocitos B y sugieren un rol diferencial en cada patología. El incremento de IL-8 previo a RTX en ambos grupos y la reducción después de la terapia en PAILES respaldan el potencial de la IL-8 como objetivo terapéutico. La heterogeneidad de la población de pacientes con PAI reafirma la importancia de la selección de subgrupos específicos en estudios futuros