Integration of T-cell clonality screening using TRBC-1 in lymphoma suspect samples by flow cytometry.

BACKGROUND: The diagnosis of T-cell non-Hodgkin lymphomas (NHL) is challenging. The development of a monoclonal antibody specific for T-cell receptor ß constant region 1 (TRBC1) provides an alternative to discriminate clonal T cells. The aim of this study was to evaluate the diagnostic potential of an anti-TRBC1 mAb for the identification of T-NHL. METHODS: We performed a cross-sectional diagnostic analytic study of samples tested for lymphoma. All samples sent for lymphoma screening were first evaluated using the standard Euroflow LST, to which a second additional custom-designed T-cell clonality assessment tube was added CD45/TRBC1/CD2/CD7/CD4/TCRγδ/CD3. Flow cytometry reports were compared with morphological and molecular tests. RESULTS: Fifty-nine patient samples were evaluated. Within the T-cell population, cut-off percentages in the CD4+ cells were from 29.4 to 54.6% and from 23.9 to 52.1% in CD8+ cells. Cut-off ratios in CD4+ T cells were from 0.33 to 1.1, and in CD8+ cells between 0.22 and 1.0. Using predefined normal cut-off values, 18 of 59 (30.5%) samples showed a restricted expression of TRBC1. A final diagnosis of a T-NHL was confirmed clinically and/or by histopathological studies in 15 of the 18 cases (83.3%). There were no cases of T-NHL by morphology/IHC with normal TRBC1 expression. Non-neoplastic patient samples behaved between predefined TRBC1 cut-off values. CONCLUSIONS: Expression of TRBC1 provides a robust method for T-cell clonality assessment, with very high sensitivity and good correlation with complementary methods. TRBC1 can be integrated into routine lymphoma screening strategies via flow cytometry.

Enfermedad relacionada a IgG4. Serie clínica de pacientes chilenos / IGG4-related disease. Report of 52 patients

BACKGROUND: IgG4-related disease (IgG4 RD) is an immune-mediated fibro-inflammatory disorder, with tissue infiltration of IgG4+ plasma cells. It causes pseudotumors, tumors, and a wide spectrum of clinical manifestations. AIM: To report the clinical, laboratory, histopathological and treatment characteristics of a group of Chilean patients with IgG4 RD. MATERIAL AND METHODS: Review of medical records of 52 patients aged 18 to 76 years with IgG4 RD seen at six medical centers. RESULTS: Elevated IgG4 serum levels (> 135 mg/dl) were found in 18 of 44 (41%) patients. There was histological confirmation of the disease in 46 patients. The most common sites of involvement were lungs, eyes and kidneys. Eighteen (35%) patients had only one organ involved, 34 (65%) patients had two organs and 13 (25%) patients had three or more organs. The involvement of two organs was significantly more common in men (p < 0.05). In patients with only one organ involvement, the most frequent location was orbital and meningeal. All patients with kidney or lung disease had multiorgan involvement. All patients received corticosteroid therapy, 67% synthetic immunosuppressants, and 16% rituximab. CONCLUSIONS: ER-IgG4 can affect any tissue. Multiorgan involvement was more common in this series, with preference for lungs, eyes and kidneys. An excellent response to steroids is characteristic of the disease, but with a high relapse rate that requires additional immunosuppression.

Respuesta inmunitaria al SARS-CoV-2 y factores asociados previo a la vacunación, en personal de salud de atención primaria en una comuna de Santiago, Chile

Resumen Introducción: La pandemia de COVID-19 surgida en China a fines de 2019, se extendió rápidamente por el mundo, con casi 600 millones de casos y 6,3 millones de fallecidos en la actualidad. Los más afectados fueron los trabajadores de la salud con al menos tres veces más riesgo que la comunidad general de contraer la enfermedad. La mayoría de los estudios sobre seroprevalencia en trabajadores de la salud, se enfocan en establecimientos de atención hospitalaria y no se ha indagado con igual intensidad sobre lo que ocurre en la Atención Primaria de Salud (APS). Objetivos: Determinar prevalencia de SARS-CoV-2 mediante anticuerpos IgG en personal de atención primaria de comuna de La Pintana y explorar sus características clínicas y factores de riesgo, previo a la vacunación en Chile. Metodología: Diseño transversal realizado en noviembre 2020. Se recogieron datos sociodemográficos y clínicos mediante entrevista cara a cara, previa firma de consentimiento. Se determinó IgG específica mediante ELISA que utiliza proteína N y S. Las diferencias entre sujetos positivos y negativos se estudiaron mediante análisis bivariado y para asociaciones encontradas, se desarrollaron modelos multivariados controlando potenciales variables de confusión. El estudio contó con la aprobación del Comité Ético Científico de la Universidad del Desarrollo. Resultados: Participaron 463 funcionarios (51,4%) encontrando prevalencia de 21,8%. Los factores de riesgo fueron edad menor, ser médico y haber sido contacto estrecho de un caso. El 22% fue asintomático. Entre quienes presentan anosmia o ageusia, la probabilidad de IgG+ fue superior a 70%. Los títulos de anticuerpos aumentan significativamente con la gravedad. Conclusiones: La prevalencia en personal de atención primaria encontrada es concordante con la evidencia previa en trabajadores de salud. La menor edad y la profesión de médico se asocian a un mayor riesgo de enfermar.

Abstract Background: The COVID-19 pandemic that emerged in Wuhan, China at the end of 2019, spread rapidly around the world with almost 600 million cases and 6.3 million deaths today. The most affected were health workers with at least three times the risk of contracting the disease than the general community. Most studies on seroprevalence in health workers focus on hospital care establishments and what happens in Primary Health Care (PHC) has not been investigated with the same intensity. Aim: To determine the prevalence of SARS-CoV-2 using IgG antibodies in primary health care personnel in La Pintana commune, risk factors and clinical characteristics, prior to vaccination in Chile. Methods: A cross-sectional design carried out in November 2020. Sociodemographic and clinical data were collected through face-to-face interviews, after providing informed consent. Specific IgG was determined by ELISA using N and S proteins. The differences between positive and negative subjects were studied using bivariate analysis and multivariate models, controlling for potential confounding variables. The study was approved by the Universidad del Desarrollo Scientific Ethics Committee. Results: 463 employees (51.4%) participated, finding a prevalence of 21.8%. The risk factors found were younger age, being a physician and having been in close contact with a case. 22% were asymptomatic. Among those with anosmia/ageusia, the probability of IgG+ was greater than 70%. Antibody titers increase with severity. Conclusions: Prevalence found in primary health care personnel is consistent with previous evidence. Younger age and medical profession are associated with a higher risk of illness.

Longitudinal assessment of SARS-CoV-2 IgG seroconversionamong front-line healthcare workers during the first wave of the Covid-19 pandemic at a tertiary-care hospital in Chile.

BACKGROUND: Healthcare workers (HCWs) are at high risk of exposure to SARS-CoV-2. Cross-sectional studies have provided variable rates of seroprevalence in HCWs. Longitudinal assessments of the serological response to Covid-19 among HCWs are crucial to understanding the risk of infection and changes in antibody titers over time. We aimed to investigate seroprevalence and risk factors associated with seroconversion in a prospective cohort of HCWs during the peak of the first wave of the Covid-19 pandemic. METHODS: We conducted a longitudinal study among 446 front-line HCWsin a tertiary-care hospital in Chile from April to July 2020. IgG was determined monthly using two different ELISAs in serum samples of HCWs, during the three-month period. In each visit, demographic data, symptoms, risk factors, and exposure risks were also assessed. RESULTS: The overall seroprevalence at the end of the study period was 24% (95% CI20.2-28.3), with 43% of seropositive HCWs reporting no prior symptoms. Seroconversion rates significantly differed over the study period, from 2.1% to as high as 8.8% at the peak of the epidemic. There were no statistically significant differences observed between HCWs in direct clinical care of patients with Covid-19 and those working in low risk areas. Antibody titers appeared to wane over time. CONCLUSIONS: HCWs were severely affected with a high rate of seroconversion that appeared to mirror the local epidemiological situation. A significant amount of participants underwent an asymptomatic infection, highlighting the need for improved surveillance policies. Antibody titers appear to wane over time; further studies to understand this finding's impact on the risk of reinfection are warranted.

Evaluation of two fluorescence immunoassays for the rapid detection of SARS-CoV-2 antigen-new tool to detect infective COVID-19 patients.

BACKGROUND: Real-Time Reverse-Transcription Polymerase Chain Reaction (RT-PCR) is currently the only recommended diagnostic method for SARS-CoV-2. However, rapid immunoassays for SARS-CoV-2 antigen could significantly reduce the COVID-19 burden currently weighing on laboratories around the world. METHODS: We evaluated the performance of two rapid fluorescence immunoassays (FIAs), SOFIA SARS Antigen FIA (Quidel Corporation, San Diego, CA, USA) and STANDARD F COVID-19 Ag FIA (SD Biosensor Inc., Gyeonggi-do, Republic of Korea), which use an automated reader. The study used 64 RT-PCR characterized clinical samples (32 positive; 32 negative), which consisted of nasopharyngeal swabs in universal transport medium. RESULTS: Of the 32 positive specimens, all from patients within 5 days of symptom onset, the Quidel and SD Biosensor assays detected 30 (93.8%) and 29 (90.6%) samples, respectively. Among the 27 samples with high viral loads (Ct ≤ 25), the two tests had a sensitivity of 100%. Specificity was 96.9% for both kits. CONCLUSION: The high performance of the evaluated FIAs indicates a potential use as rapid and PCR-independent tools for COVID-19 diagnosis in early stages of infection. The excellent sensitivity to detect cases with viral loads above ~106 copies/mL (Ct values ≤ 25), the estimated threshold of contagiousness, suggests that the assays might serve to rapidly identify infective individuals.

First Report of Tocilizumab Use in a Cohort of Latin American Patients Hospitalized for Severe COVID-19 Pneumonia.

Introduction/objectives: An interleukin-6 inhibition strategy could be effective in selected COVID-19 patients. The objective is to present our experience of tocilizumab use in patients with severe COVID-19. Methods: Observational retrospective cohort study. Hospitalized patients were evaluated by our multidisciplinary team for eventual use of tocilizumab. Patients with progressive ventilatory impairment and evidence of a hyperinflammatory state despite usual treatment received tocilizumab 8 mg/kg intravenous (maximum dose 800 mg), in addition to standard treatment. The use and time of use of mechanical ventilation (MV), the change of the Alveolar-arterial (A-a) gradient, of the ratio of arterial oxygen partial pressure to fractional inspired oxygen (PaO2/FiO2) and of inflammation laboratory parameters after 72 h of tocilizumab use was evaluated. Results: 29 patients received tocilizumab. 93.1% were men, 37.9% were obese, and 34.5% had hypertension. Of the 20 patients who were not on MV when receiving tocilizumab, 11 required non-invasive MV, for an average of 5 days, and one of them required intubation. A-a gradient, PaO2/FiO2, and inflammation parameters improved significantly. A better lymphocyte count, which improved significantly after tocilizumab use, was significantly associated with less use of MV. Five patients presented positive culture samples after tocilizumab, three being of clinical significance. A lower lymphocyte count was associated with having a positive culture. No other significant adverse events were seen. Conclusion: Our study suggests the utility and shows the safety of tocilizumab use in COVID-19 patients who have respiratory failure and evidence of hyperinflammation. Lymphocyte improvement was a predictor of good response.

Evaluation of a novel antigen-based rapid detection test for the diagnosis of SARS-CoV-2 in respiratory samples.

OBJECTIVES: In the context of the coronavirus disease 2019 (COVID-19) pandemic, the development and validation of rapid and easy-to-perform diagnostic methods are of high priority. This study was performed to evaluate a novel rapid antigen detection test (RDT) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in respiratory samples. METHODS: The fluorescence immunochromatographic SARS-CoV-2 antigen test (Bioeasy Biotechnology Co., Shenzhen, China) was evaluated using universal transport medium with nasopharyngeal (NP) and oropharyngeal (OP) swabs from suspected COVID-19 cases. Diagnostic accuracy was determined in comparison to SARS-CoV-2 real-time (RT)-PCR. RESULTS: A total of 127 samples were included; 82 were RT-PCR-positive. The median patient age was 38 years, 53.5% were male, and 93.7% were from the first week after symptom onset. Overall sensitivity and specificity were 93.9% (95% confidence interval 86.5-97.4%) and 100% (95% confidence interval 92.1-100%), respectively, with a diagnostic accuracy of 96.1% and Kappa coefficient of 0.9. Sensitivity was significantly higher in samples with high viral loads. CONCLUSIONS: The RDT evaluated in this study showed a high sensitivity and specificity in samples mainly obtained during the first week of symptoms and with high viral loads, despite the use of a non-validated sample material. The assay has the potential to become an important tool for early diagnosis of SARS-CoV-2, particularly in situations with limited access to molecular methods.

Esofagitis eosinofílica: diagnóstico y manejo / Diagnosis and management of eosinophilic esophagitis

Eosinophilic esophagitis (EoE) is a chronic, immune-mediated disease, induced by food allergens, clinically characterized by symptoms of esophageal dysfunction. Pathologically there is a predominant eosinophilic inflammation. This disease is relatively new, and its definitions have evolved over time. Its prevalence and incidence are increasing and causes clinical problems both in children and adults. Its symptoms include food impaction, dysphagia, symptoms that resemble gastroesophageal reflux, abdominal pain, and vomiting. It can also have extra-digestive symptoms such as rhinosinusitis, chronic cough, recurrent croup and hoarseness. EoE can be associated with other atopic conditions, such as asthma, eczema and food allergies. The diagnosis is made by the analysis of endoscopic biopsies (> 15 eosinophils per high power field). Proton pump inhibitors (PPIs) are currently accepted as a treatment for EoE. The clinical and pathological improvement with the use PPIs ceased to be a criterion to define Esophageal eosinophilia responsive to PPIs as a differential diagnosis, since this condition is currently considered within the EoE spectrum. There are three main treatment approaches for EoE: diet, drugs and dilation. Its diagnosis and early treatment are key to avoid or delay its complications, such as stenosis and severe esophageal dysfunction.

[Diagnosis and management of eosinophilic esophagitis]. / Esofagitis eosinofílica: diagnóstico y manejo.

Eosinophilic esophagitis (EoE) is a chronic, immune-mediated disease, induced by food allergens, clinically characterized by symptoms of esophageal dysfunction. Pathologically there is a predominant eosinophilic inflammation. This disease is relatively new, and its definitions have evolved over time. Its prevalence and incidence are increasing and causes clinical problems both in children and adults. Its symptoms include food impaction, dysphagia, symptoms that resemble gastroesophageal reflux, abdominal pain, and vomiting. It can also have extra-digestive symptoms such as rhinosinusitis, chronic cough, recurrent croup and hoarseness. EoE can be associated with other atopic conditions, such as asthma, eczema and food allergies. The diagnosis is made by the analysis of endoscopic biopsies (> 15 eosinophils per high power field). Proton pump inhibitors (PPIs) are currently accepted as a treatment for EoE. The clinical and pathological improvement with the use PPIs ceased to be a criterion to define Esophageal eosinophilia responsive to PPIs as a differential diagnosis, since this condition is currently considered within the EoE spectrum. There are three main treatment approaches for EoE: diet, drugs and dilation. Its diagnosis and early treatment are key to avoid or delay its complications, such as stenosis and severe esophageal dysfunction.

The Prevalence of Rheumatoid Arthritis in Chile: A Nationwide Study Performed as Part of the National Health Survey.

OBJECTIVE: Genetic and environmental backgrounds influence the development of rheumatoid arthritis (RA). In Latin America, epidemiologic data are scarce. We aimed to determine the prevalence of RA in Chile in a population-based study. METHODS: The National Health Survey was a cross-sectional household survey with a stratified multistage probability sample of 6233 participants performed between August 2016 and March 2017. A screening instrument for RA was applied to a random sample of 3847 subjects > 30 years old. Positive screening was defined by at least 1 of the following: 2 swollen joints for at least 4 consecutive weeks (past/present), and/or a diagnosis of arthritis in the past. Individuals with positive screening had rheumatoid factor, anticitrullinated protein antibodies, and C-reactive protein measured, as well as clinical examination performed by a rheumatologist. Self-report of doctor-diagnosed RA was also performed. RESULTS: The screening questionnaire was applied to 2998 subjects. A positive screening was found for 783 (22.1%). Among subjects with positive screening, 493 (66%) had a clinical evaluation performed by a rheumatologist. Using the American College of Rheumatology/European League Against Rheumatism 2010 classification criteria, prevalence was 0.6% (95% CI 0.3-1.2). Prevalence was higher in women, and 3.3% of subjects self-reported having RA. CONCLUSION: According to this national population-based study, RA prevalence in Chile is 0.6% (0.3-1.2), a value similar to what has been found in developed countries and slightly lower than some Latin American countries. Self-reporting leads to overestimating RA.

[Consensus of infectious complications in patients treated with selected biological therapies: first Part]. / Consenso sobre riesgo de complicaciones infecciosas en pacientes usuarios de medicamentos biológicos seleccionados. Parte I.

The use of biological therapies has meant a great improvement in the management of several conditions like autoimmune, neoplastic or others diseases. Although its use has implied significant improvements in the prognosis of these diseases, it is not exempt from complications: infectious diseases as one of them. The objective of this consensus was to evaluate, from an infectious viewpoint, the safeness of the most frequently used biological therapies and give recommendations for the prevention of infections in patients treated with these drugs. These recommendations were based on the highest quality evidence available for the selected biologics. The consensus counts of two manuscripts. This first part details the risks of developing infectious complications depending on the type of biological used for a certain pathology. This evaluation included a broad search in MEDLINE and Epistemonikos of systematic reviews and meta-analyzes of controlled clinical trials and casecontrol examining post-treatment infections with anti-TNF alpha, anti-CD20, anti-CD52, CTLA4-Ig and anti-integrins. The research was complemented by a review of: multicentre cohorts of biological users, the MMWR of the CDC, Atlanta, U.S.A., and national registers and scientific societies in which infectious complications derived from the use of biological therapies were mentioned.

Consenso sobre riesgo de complicaciones infecciosas en pacientes usuarios de medicamentos biológicos seleccionados. Parte I / Consensus of infectious complications in patients treated with selected biological therapies: first Part

Resumen La incorporación de terapias biológicas ha significado un gran avance en el manejo de diversas patologías de origen autoinmune, neoplásico u otros. Si bien su uso ha implicado mejoras significativas en el pronóstico de estas enfermedades, no está exento de complicaciones, entre estas, las infecciosas. El objetivo de este consenso fue evaluar el perfil de seguridad, desde la mirada infectológica, de las terapias biológicas de uso más frecuente y dar recomendaciones para la prevención de infecciones en pacientes tratados con ellas, basándose en la evidencia de mayor calidad disponible para los biológicos seleccionados. El consenso cuenta de dos manuscritos. Esta primera parte detalla los riesgos de desarrollar complicaciones infecciosas dependiendo del tipo de biológico utilizado para determinada patología. La revisión incluyó búsqueda amplia en MEDLINE y Epistemonikos de revisiones sistemáticas y meta-análisis de estudios clínicos controlados y caso/control que examinaban infecciones posteriores al tratamiento con anti-TNF alfa, anti-CD20, anti-CD52, CTLA4-Ig y anti-integrinas. Esta búsqueda se complementó con revisión de cohortes multicéntricas de usuarios de biológicos, del MMWR del CDC, Atlanta, E.U.A. y de registros nacionales y/o de sociedades científicas en la que se hiciera mención a complicaciones infecciosas derivadas del uso de biológicos.

The use of biological therapies has meant a great improvement in the management of several conditions like autoimmune, neoplastic or others diseases. Although its use has implied significant improvements in the prognosis of these diseases, it is not exempt from complications: infectious diseases as one of them. The objective of this consensus was to evaluate, from an infectious viewpoint, the safeness of the most frequently used biological therapies and give recommendations for the prevention of infections in patients treated with these drugs. These recommendations were based on the highest quality evidence available for the selected biologics. The consensus counts of two manuscripts. This first part details the risks of developing infectious complications depending on the type of biological used for a certain pathology. This evaluation included a broad search in MEDLINE and Epistemonikos of systematic reviews and meta-analyzes of controlled clinical trials and casecontrol examining post-treatment infections with anti-TNF alpha, anti-CD20, anti-CD52, CTLA4-Ig and anti-integrins. The research was complemented by a review of: multicentre cohorts of biological users, the MMWR of the CDC, Atlanta, U.S.A., and national registers and scientific societies in which infectious complications derived from the use of biological therapies were mentioned.

Innate Immune Cells' Contribution to Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by the presence of autoantibodies against nuclear antigens, immune complex deposition, and tissue damage in the kidneys, skin, heart and lung. Because of the pathogenic role of antinuclear antibodies and autoreactive T cells in SLE, extensive efforts have been made to demonstrate how B cells act as antibody-producing or as antigen-presenting cells that can prime autoreactive T cell activation. With the discovery of new innate immune cells and inflammatory mediators, innate immunity is emerging as a key player in disease pathologies. Recent work over the last decade has highlighted the importance of innate immune cells and molecules in promoting and potentiating SLE. In this review, we discuss recent evidence of the involvement of different innate immune cells and pathways in the pathogenesis of SLE. We also discuss new therapeutics targets directed against innate immune components as potential novel therapies in SLE.

Smoking promotes exacerbated inflammatory features in dendritic cells of Chilean rheumatoid arthritis patients.

BACKGROUND: The dual potential to promote tolerance or inflammation when facing self-antigens makes dendritic cells (DCs) fundamental players in autoimmunity. There is an association between smoking and DCs maturation in patients with rheumatoid arthritis (RA). However, ethnicity is a key factor in autoimmune disorders. AIM: To evaluate phenotypic and functional alterations of DCs obtained from Chilean patients with RA as compared to healthy controls (HC). In second term, to compare the inflammatory behaviour of DCs between smoker and non-smoker patients. MATERIAL AND METHODS: Monocyte-derived DCs and T-cells were obtained from blood samples isolated from 30 HC and 32 RA-patients, 14 of which were currently smokers and 18 non-smokers. Several maturation surface markers were evaluated in DCs, including HLA-DR, CD40, CD80, CD83 and CD86. Furthermore, autologous co-cultures of DCs and T-cells were carried out and then T-cell proliferation, and expansion of Th1, Th17 and Tregs were analysed. RESULTS: Compared with HC, RA-patients displayed increased HLA-DR expression in DCs, which was manifested mainly in patients with moderate-to- high disease activity scores (DAS28). Furthermore, RA-patients presented a stronger Th17-expansion and a correlation between DAS28 and Th1-expansion. Both effects were mainly observed in patients in remission or with a low DAS28. Moreover, smoker RA-patients displayed enhanced HLA-DR and CD83 expression in DCs as well as an exacerbated Th17-expansion and a correlation between DAS28 and Th1-expansion. CONCLUSIONS: These findings suggest that smoking enhances the inflammatory behaviour of DCs and the consequent Th1 and Th17-mediated response in patients with RA.

[Renal involvement in antineutrophil cytoplasmic antibodies (ANCA) associated vasculitides. Recommendations of the Chilean Societies of Nephrology and Rheumatology]. / Compromiso renal en vasculitis asociadas a anticuerpos anticitoplasma de neutrófilos. Recomendaciones de consenso de las Sociedades Chilenas de Nefrología y Reumatología.

Renal involvement is a frequent complication in antineutrophil cytoplasmic antibodies (ANCA)associated vasculitides, adding morbidity and mortality, such as chronic kidney disease and the need for renal replacement therapy. With the aim of reaching a consensus on relevant issues regarding the diagnosis, treatment and follow-up of patients with these diseases, the Chilean Societies of Nephrology and Rheumatology formed a working group that, based on a critical review of the available literature and their experience, raised and answered consensually a set of questions relevant to the subject. This document includes aspects related to the clinical diagnosis, the histological characteristics, the therapeutic alternatives to induce and maintain the remission of the disease, relapse surveillance strategies and complementary therapies.

Role of dendritic cells in peanut allergy.

INTRODUCTION: The prevalence of peanut allergy (PA) has increased, affecting approximately 1.1% of children in Western countries. PA causes life-threatening anaphylaxis and frequently persists for life. There are no standardized curative therapies for PA, and avoidance of peanuts remains the main therapeutic option. A better understanding of the pathogenesis of PA is essential to identify new treatment strategies. Intestinal dendritic cells (DCs) are essential in the induction and maintenance of food tolerance because they present dietary allergens to T cells, thereby directing subsequent immune responses. Areas covered: In this review, we discuss the factors related to the acquisition of oral tolerance to peanut proteins. We focus on intestinal DC-related aspects, including the latest advances in the biology of intestinal DC subtypes, effect of tolerance-inducing factors on DCs, effect of dietary components on oral tolerance, and role of DCs in peanut sensitization. Expert commentary: Given the increasing prevalence of PA, difficulty of avoiding peanut products, and the potentially serious accidental reactions, the development of novel therapies for PA is needed. The ability of DCs to trigger tolerance or immunity makes them an interesting target for new treatment strategies against PA.

Smoking promotes exacerbated inflammatory features in dendritic cells of Chilean rheumatoid arthritis patients / El tabaco exacerba características inflamatorias en células dendríticas de pacientes chilenos con artritis reumatoide

ABSTRACT Background: The dual potential to promote tolerance or inflammation when facing self-antigens makes dendritic cells (DCs) fundamental players in autoimmunity. There is an association between smoking and DCs maturation in patients with rheumatoid arthritis (RA). However, ethnicity is a key factor in autoimmune disorders. Aim: To evaluate phenotypic and functional alterations of DCs obtained from Chilean patients with RA as compared to healthy controls (HC). In second term, to compare the inflammatory behaviour of DCs between smoker and non-smoker patients. Material and Methods: Monocyte-derived DCs and T-cells were obtained from blood samples isolated from 30 HC and 32 RA-patients, 14 of which were currently smokers and 18 non-smokers. Several maturation surface markers were evaluated in DCs, including HLA-DR, CD40, CD80, CD83 and CD86. Furthermore, autologous co-cultures of DCs and T-cells were carried out and then T-cell proliferation, and expansion of Th1, Th17 and Tregs were analysed. Results: Compared with HC, RA-patients displayed increased HLA-DR expression in DCs, which was manifested mainly in patients with moderate-to- high disease activity scores (DAS28). Furthermore, RA-patients presented a stronger Th17-expansion and a correlation between DAS28 and Th1-expansion. Both effects were mainly observed in patients in remission or with a low DAS28. Moreover, smoker RA-patients displayed enhanced HLA-DR and CD83 expression in DCs as well as an exacerbated Th17-expansion and a correlation between DAS28 and Th1-expansion. Conclusions: These findings suggest that smoking enhances the inflammatory behaviour of DCs and the consequent Th1 and Th17-mediated response in patients with RA

Introducción: El potencial dual que poseen para promover tolerancia o inflamación ante antígenos propios, hace de las células dendríticas (CDs) actores fundamentales en el desarrollo de autoinmunidad. Existe una asociación entre fumar y la maduración de las CDs en pacientes con artritis reumatoide (AR). No obstante, la etnicidad es un factor clave a considerar en desórdenes autoinmunes. Objetivos: Comparar las alteraciones fenotípicas y funcionales de las CDs obtenidas desde pacientes Chilenos con AR y controles sanos (CS). Además, analizamos las diferencias en el comportamiento inflamatorio que existe entre las CDs obtenidas de pacientes fumadores y CS. Materiales y Métodos: Se obtuvieron CDs derivadas de monocitos y células T desde muestras de sangre aisladas de 30 CS y 32 pacientes con AR, 14 de los cuales eran fumadores y 18 no fumadores. Se evaluaron marcadores de maduración en la superficie de las CDs: HLA-DR, CD40, CD80, CD83 y CD86. Además, se realizaron co-cultivos autólogos de células T y CDs, analizando la proliferación de células T, y la expansión de células Th1, Th17 y Tregs. Resultados: En comparación con los CS, los pacientes AR mostraron un aumento de la expresión de HLA-DR en las CDs, principalmente en los individuos con DAS28 moderado-alto. Los pacientes con AR presentaron una mayor expansión de células Th17 y una correlación entre el DAS28 y la expansión de células Th1, ambos efectos manifestados principalmente en los individuos con un DAS28 bajo o en remisión. Además, los pacientes con AR fumadores mostraron un aumento en la expresión de HLA-DR y CD83 en las CDs y una expansión de células Th17 exacerbada así como una correlación entre el DAS28 y la expansión de células Th1. Conclusiones: Nuestros resultados sugieren que fumar favorece el comportamiento inflamatorio de las CDs y en consecuencia la inducción de respuestas mediadas por células Th1 y Th17 en los pacientes Chilenos con AR.

Compromiso renal en vasculitis asociadas a anticuerpos anticitoplasma de neutrófilos. Recomendaciones de consenso de las Sociedades Chilenas de Nefrología y Reumatología / Renal involvement in antineutrophil cytoplasmic antibodies (ANCA) associated vasculitides. Recommendations of the Chilean Societies of Nephrology and Rheumatology

Renal involvement is a frequent complication in antineutrophil cytoplasmic antibodies (ANCA)associated vasculitides, adding morbidity and mortality, such as chronic kidney disease and the need for renal replacement therapy. With the aim of reaching a consensus on relevant issues regarding the diagnosis, treatment and follow-up of patients with these diseases, the Chilean Societies of Nephrology and Rheumatology formed a working group that, based on a critical review of the available literature and their experience, raised and answered consensually a set of questions relevant to the subject. This document includes aspects related to the clinical diagnosis, the histological characteristics, the therapeutic alternatives to induce and maintain the remission of the disease, relapse surveillance strategies and complementary therapies.

Hemicorea como primera manifestación clínica de lupus eritematoso sistémico / Hemichorea as first clinical manifestation of systemic lupus erythematosus

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