Cesar Ramos-Remus

Type I Interferon Gene Response Is Increased in Early and Established Rheumatoid Arthritis and Correlates with Autoantibody Production

Background Rheumatoid arthritis (RA) is an inflammatory debilitating disease that affects the joints in the early and productive phases of an individual’s life. Several cytokines have been linked to the disease pathogenesis and are known to contribute to the inflammatory state characteristic of RA. The participation of type I interferon (IFN) in the pathogenesis of the disease has been already described as well as the identity of the genes that are regulated by this molecule, which are collectively known as the type I IFN signature. These genes have several functions associated with apoptosis, transcriptional regulation, protein degradation, Th2 cell induction, B cell proliferation, etc. This article evaluated the expression of several genes of the IFN signature in different stages of disease and their correlation with the levels of anticitrullinated protein antibodies (ACPA) anticarbamylated protein (Anti-CarP) antibodies. Methods Samples from individuals with early and established RA, high-risk individuals (ACPA+ and ACPA−), and healthy controls were recruited at “Unidad de Artritis y Rheumatismo” (Rheumatism and Arthritis Unit) in Guadalajara Jalisco Mexico. Determinations of ACPA were made with Eurodiagnostica ACPA plus kit. Anti-CarP determinations were made according to previously described protocols. RNA was isolated, and purity and integrity were determined according to RNA integrity number >6. Gene expression analysis was made by RT-qPCR using specific primers for mRNAs of the type I IFN signature. Relative gene expression was calculated according to Livak and Schmitgen. Results Significant differences in gene expression were identified when comparing the different groups for MXA and MXB (P < 0.05), also when comparing established RA and ACPA− in both IFIT 1 and G15. An increased expression of ISG15 was identified (P < 0.05), and a clear tendency toward increase was identified for HERC5. EPSTRI1, IFI6, and IFI35 were found to be elevated in the chronic/established RA and early RA (P < 0.05). Significant correlations were identified for the IFN signature genes with the levels of ACPA and anti-CarP (P < 0.05). Conclusion Our data confirm previous observations in the role of IFN signature and the pathogenesis of RA. Also, we provide evidence of an association between several genes of the IFN signature (that regulate Th2 cells and B cell proliferation) with the levels of anti-CarP antibodies and ACPA.

Legibilidad, relevancia y calidad de la información en español en la Web para pacientes con artritis reumatoide

BACKGROUND Education is a major health determinant and one of the main independent outcome predictors in rheumatoid arthritis (RA). The use of the Internet by patients has grown exponentially in the last decade. OBJECTIVE To assess the characteristics, legibility and quality of the information available in Spanish in the Internet regarding to rheumatoid arthritis. MATERIAL AND METHODS The search was performed in Google using the phrase rheumatoid arthritis. Information from the first 30 pages was evaluated according to a pre-established format (relevance, scope, authorship, type of publication and financial objective). The quality and legibility of the pages were assessed using two validated tools, DISCERN and INFLESZ respectively. Data extraction was performed by senior medical students and evaluation was achieved by consensus. RESULTS The Google search returned 323 hits but only 63% were considered relevant; 80% of them were information sites (71% discussed exclusively RA, 44% conventional treatment and 12% alternative therapies) and 12.5% had a primary financial interest. 60% of the sites were created by nonprofit organizations and 15% by medical associations. Web sites posted by medical institutions from the United States of America were better positioned in Spanish (Arthritis Foundation 4th position and American College of Rheumatology 10th position) than web sites posted by Spanish speaking countries. CONCLUSIONS There is a risk of disinformation for patients with RA that use the Internet. We identified a window of opportunity for rheumatology medical institutions from Spanish-speaking countries to have a more prominent societal involvement in the education of their patients with RA.

Analysis of miRNA expression in patients with rheumatoid arthritis during remission and relapse after a 5-year trial of tofacitinib treatment

&NA; The physiopathology of rheumatoid arthritis (RA) is mediated by proinflammatory cytokines, some of which are regulated by the JAK/STAT pathway. Tofacitinib is a JAK inhibitor, but its role in the regulation of microRNAs (miRNAs) is unknown. There is also no information regarding the role of miRNAs in the clinical relapse/remission of RA. The present project aims to identify a signature profile of miRNA expression in a subgroup of RA patients who had to discontinue tofacitinib treatment (because of the ending of a 5‐year open‐label clinical trial) and to describe the expression of miRNAs during RA remission or flare‐up. The relative expression of 61 miRNAs was determined in serum samples with the Firefly™ BioWorks assay. Statistical analysis was performed by means of Students t‐test and heatmap analysis was performed with Firefly™ Analysis Workbench software and in the software GraphPad® Prism v5.0. Target prediction and Gene Ontology analysis were carried out using bioinformatic tools. We found a distinctive signature of miRNA expression associated with relapse, featuring upregulated expression of hsa‐miR‐432‐5p (p < 0.05). We also found upregulation of hsa‐miR‐194‐5p (p < 0.05) in samples of patients with RA flare‐up. Gene Ontology analysis of the target genes for hsa‐miR‐432‐5p was performed to identify relevant pathways associated with relapse; the implications of these pathways in the physiopathology of RA are discussed. Tofacitinib treatment does not have a direct effect on the expression of measured miRNAs. The changes in hsa‐miR‐432‐5p and hsa‐miR‐194‐5p are associated with the regulation of proinflammatory pathways and RA flare‐up. Highlightshsa‐miR‐432‐5p is downregulated in patients achieving clinical remission.Treatment with Tofacitinib does not affect miRNA expression directly.Patients with relapse have a specific miRNA signature as measured by Firefly Bioworks.hsa‐miR‐194‐5p is upregulated during RA flare‐up patients suggesting that this miRNA could be used as a biomarker for relapse.

Equidad, validez y confiabilidad del Examen Nacional para Aspirantes a Residencias Médicas (ENARM): oportunidades para mejorar

Senor editor: La formacion de recursos humanos de alta calidad en las especialidades medicas es de gran importancia para la sociedad. El proceso inicia cada ano con la seleccion de los candidatos a traves del Examen Nacional para Aspirantes a Residencias Medicas (ENARM). En 2016, mas de 36 000 medicos generales compitieron a traves del ENARM por una de las, aproximadamente, 8 250 plazas ofertadas. Segun fuentes oficiales, algunos de los atributos conferidos al proceso del ENARM incluyen “equitativo”, “transparente”, “objetivo” y “valido”.

Is gout an easy-to-treat disease? The importance of health determinants

The patient is a 60-year old man we attended during a rheumatology campaign at his hometown, Etzatlan, Mexico. He has a 30-year history of gout and presented widespread tophus formation with extensive structural damage (Fig. 1). Based on the model of health determinants described by the WHO,1 we depict the failures that explain why a supposedly easy-to-treat disease2 progressed to polyarticular chronic tophaceous gout with multidimensional impact. Genes predispose to the disease but do not determine outcomes. Regarding education and individual lifestyle, the patient had 2 years of schooling, frequently drank alcohol, and had a strong internal locus of control. Regarding healthcare services, the patient attended over 25 general practitioners (GPs), receiving different prescriptions and several contradictory indications, mainly on how to take allopurinol which varied from daily suboptimal doses to periodic use as “prophylaxis” when the patient planned to drink alcohol. The patient visited a rheumatologist once, who explained the disease in detail and how to treat it. But the patient did not understand and

AB1136 The age of onset of rheumatoid arthritis correlates with air pollution and health expenditure: results from multinational databases

Background Environmental variables contribute up to half of the variation in the rheumatoid arthritis (RA) susceptibility. We have recently reported that the age of RA onset (RAo) varies across latitudes around the world, starting younger around the Tropic of Cancer (1). Latitude gradients have been used as a surrogate for studying the influence of the environment on the risks of disease in order to generate hypotheses for further investigation. Objectives This is an exploratory study to assess whether the age of RAo correlates with tropospheric pollutants (2), electromagnetic fields, Inequality-adjusted Human Development Index (I-HDI) and Health Expenditures as per national census of participating countries. Methods The age of RAo was obtained from the GEO-RA group database that involves 2,481 patients from 41 countries. Information of the tropospheric pollutant PM10 (particulate matter 10μ), the I-HDI, and Health Expenditures per capita was obtained from the World Health Organizations reports. The average of each countrys electromagnetic fields (nanotesla, nT) from the past 50 years was calculated using geographic coordinates per country through the magnetic field calculator of The National Centers of Environmental Information. Pearsons correlation and linear regression were used to evaluate the correlation of these environmental variables with the age of RAo by country. Results Complete data sets were available in 35 of the 41 countries. Overall, the mean age of RAo was 44±4.8 years, the annual average of PM10 of 57.5±39.3 μg/m3, the Health Expenditure per capita of US

Fifteen-year trend in information on the World Wide Web for patients with rheumatoid arthritis: evolving, but opportunities for improvement remain.

2,212±2,742, and the electromagnetic fields of 41,900±8,720 nT. The age of RAo was younger in countries with high PM10 levels (r= -0.61, p<0.01), high inequality (I-HDI, r=0.59, p<0.01), and low Health Expenditure per capita (r=0.61, p<0.01); the age of RAo did not correlate with nT. A significant linear regression equation was found [F(2,32)=13.61, p<0.01, R2=0.46] in the age of RAo, Health Expenses per capita (β=0.0007; CI 95% 0.00004 to 0.001) and PM10 levels (β=-0.044; CI 95% -0.085 to -0.002). Conclusions The tropospheric pollutant PM10 and the components of the Health Expenditure per capita such as the provision of health services, family planning activities and nutrition activities are variables worth to further study through hypothesis-testing designs. References GEO-RA Group. Latitude gradient influences the age of onset of rheumatoid arthritis: a worldwide survey. Clin Rheumatol 2016. DOI: 10.1007/s10067–016–3481–9. Essouma M, Noubiap JJ. Is air pollution a risk factor for rheumatoid arthritis? J Inflamm (Lond) 2015; 12:48. DOI: 10.1186/s12950–015–0092–1. Disclosure of Interest None declared