Role of CXCL13 and CCL20 in the recruitment of B cells to inflammatory foci in chronic arthritis

Background: B cells exert their pathogenic action in rheumatoid arthritis (RA) locally in the synovium. This study was undertaken to elucidate the chemokines responsible for the recruitment of B cells in the inflamed synovium, taking into account that the rich chemokine milieu present in the synovial tissue can fine-tune modulate discrete chemokine receptors. Methods: Expression levels of chemokine receptors from the CC and CXC family, as well as CD27, were assessed by flow cytometry in CD20+ mononuclear cells isolated from the peripheral blood (PB) and synovial fluid (SF) of RA and psoriatic arthritis patients. Transwell experiments were used to study migration of B cells in response to a chemokine or in the presence of multiple chemokines. Results: B cells from the SF of arthritis patients showed a significant increase in the surface expression of CCR1, CCR2, CCR4, CCR5 and CXCR4 with respect to PB. Conversely, SF B cells expressed consistently lower amounts of CXCR5, CXCR7 and CCR6, independent of CD27 expression. Analysis of permeabilized B cells suggested internalization of CXCR5 and CCR6 in SF B cells. In Transwell experiments, CCL20 and CXCL13, ligands of CCR6 and CXCR5, respectively, caused a significantly higher migration of B cells from PB than of those from SF of RA patients. Together, these two chemokines synergistically increased B-cell migration from PB, but not from SF. Conclusions: These results suggest that CXCL13 and CCL20 might play major roles in RA pathogenesis by acting singly on their selective receptors and synergistically in the accumulation of B cells within the inflamed synovium

Prevalence of Symptomatic Axial Osteoarthritis Phenotypes in Spain and Associated Socio-Demographic, Anthropometric, and Lifestyle Variables

Epidemiology of RMDFinanciado para publicación en acceso aberto: Universidade da Coruña/CISUG[Abstract] Objective. Axial osteoarthritis (OA) is a common cause of back and neck pain, however, few studies have examined its prevalence. The aim was to estimate the prevalence and the characteristics of symptomatic axial OA in Spain. Methods. EPISER2016 is a cross-sectional multicenter population-based study of people aged 40 years or older. Subjects were randomly selected using multistage stratified cluster sampling. Participants were contacted by telephone to complete rheumatic disease screening questionnaires. Two phenotypes were analyzed, patients with Non-exclusive axial OA (NEA-OA) and Exclusive axial OA (EA-OA). To calculate the prevalence and its 95% confidence interval (CI), the sample design was considered and weighting was calculated according to age, sex and geographic origin. Results. Prevalence of NEA-OA by clinical or clinical-radiographic criteria was 19.17% (95% CI: 17.82–20.59). The frequency of NEA-OA increased with age (being 3.6 times more likely in patients aged 80 s or more than in those between 40 and 49 years) and body mass index. It was significantly more frequent in women, as well as in the center of Spain. It was less frequent in those with a higher level of education. Lumbar OA was more frequent than cervical OA. This difference grew with increasing age and was not associated with gender. It was also greater in overweight and obese subjects. Conclusions. This is the first study on the prevalence of axial OA phenotypes in Europe describing the associated socio-demographic, anthropometric, and lifestyle variables.Open Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature. EPISER2016 was supported by Celgene, Gebro Pharma, Merck Sharp & Dohme in Spain, Pfizer, and Sanofi-Aventis, none of whom had any role in the study design, data collection, data analysis, interpretation, or writing of this manuscript. MS was financed via the Rio Hortega Contract—Health Research Fund (CM17/00101), the Sanitary Research Fund integrated in the National Plan of Scientific Program, Technological Development and Innovation 2013–2016 and funded by the ISCIII-Subdirectorate General Evaluation and Promotion of Research-European Regional Development Fund (ERDF) "A way of making Europe

Association between severity of periodontitis and clinical activity in rheumatoid arthritis patients: a case–control study

Abstract Background A high prevalence of periodontitis has been reported in rheumatoid arthritis (RA) patients, although the strength of this association, its temporal link and the possible relationship between the severity of periodontitis and RA disease activity remain unclear. The objective of this work was to investigate whether periodontitis is associated with RA and whether periodontitis severity is linked to RA disease activity. Methods This case–control study included 187 patients diagnosed with RA and 157 control patients without inflammatory joint disease. RA disease activity and severity were evaluated by the Disease Activity Score 28, the Simplified Disease Activity Index, the Clinical Disease Activity Index, rheumatoid factor, anti-citrullinated protein antibody titers, the erythrocyte sedimentation rate, C-reactive protein, presence of extra-articular manifestations and type of RA therapy. Exposure severity was assessed by the following periodontal parameters: plaque index, bleeding on probing, probing pocket depth and clinical attachment levels. Sociodemographic variables and comorbidities were evaluated as confounding variables. Outcome and exposure variables were compared by both parametric and nonparametric tests, and possible associations were assessed through regression analysis with a calculation for the adjusted odds ratio (OR). Results A significant association was demonstrated between periodontitis and RA with an adjusted OR of 20.57 (95% CI 6.02–70.27, p < 0.001). Compared with controls, all parameters related to periodontal status (plaque index, bleeding on probing, probing pocket depth and clinical attachment levels) were significantly worse in RA patients (p < 0.001). Periodontitis severity was significantly associated with RA disease activity (p < 0.001), showing in an ordinal logistic regression model an association between periodontal severity and disease activity with an adjusted OR of 2.66 (95% CI 1.24–5.74, p = 0.012). Conclusion A significant association was demonstrated between periodontitis and RA, independent of other confounders. This association was more evident in patients with pronounced periodontal disease and higher RA disease activity

Role of CXCL13 and CCL20 in the recruitment of B cells to inflammatory foci in chronic arthritis

Abstract Background B cells exert their pathogenic action in rheumatoid arthritis (RA) locally in the synovium. This study was undertaken to elucidate the chemokines responsible for the recruitment of B cells in the inflamed synovium, taking into account that the rich chemokine milieu present in the synovial tissue can fine-tune modulate discrete chemokine receptors. Methods Expression levels of chemokine receptors from the CC and CXC family, as well as CD27, were assessed by flow cytometry in CD20+ mononuclear cells isolated from the peripheral blood (PB) and synovial fluid (SF) of RA and psoriatic arthritis patients. Transwell experiments were used to study migration of B cells in response to a chemokine or in the presence of multiple chemokines. Results B cells from the SF of arthritis patients showed a significant increase in the surface expression of CCR1, CCR2, CCR4, CCR5 and CXCR4 with respect to PB. Conversely, SF B cells expressed consistently lower amounts of CXCR5, CXCR7 and CCR6, independent of CD27 expression. Analysis of permeabilized B cells suggested internalization of CXCR5 and CCR6 in SF B cells. In Transwell experiments, CCL20 and CXCL13, ligands of CCR6 and CXCR5, respectively, caused a significantly higher migration of B cells from PB than of those from SF of RA patients. Together, these two chemokines synergistically increased B-cell migration from PB, but not from SF. Conclusions These results suggest that CXCL13 and CCL20 might play major roles in RA pathogenesis by acting singly on their selective receptors and synergistically in the accumulation of B cells within the inflamed synovium

Prevalencia de artrosis sintomática en España: Estudio EPISER2016

Introduction: The Spanish Society of Rheumatology carried out the EPISER2000 study in 2000 to determine the prevalence of osteoarthritis and other rheumatic diseases in the Spanish population. Recent sociodemographic changes and lifestyle habits in Spain justified updating the epidemiological data on osteoarthritis and other rheumatic diseases (EPISER2016-study). Objective: To estimate the prevalence of symptomatic osteoarthritis of the cervical spine, lumbar spine, hip, knee and hand in the adult population in Spain. Material and methods: Cross-sectional population-based study. A multistage and stratified random cluster sampling was carried out. The participants were contacted by telephone to complete an osteoarthritis screening questionnaire. A rheumatologist confirmed or discarded the diagnosis. The ACR-clinical-criteria were used to diagnose hand-osteoarthritis and the ACR-clinical-radiological criteria to diagnose knee- and hip-osteoarthritis. To estimate the prevalence and its 95% confidence interval, weights were calculated according to the probability of selection in each of the sampling stages. Results: The prevalence of osteoarthritis in Spain in one or more of the locations studied was 29.35%. The prevalence of cervical-osteoarthritis was 10.10% and of lumbar-osteoarthritis 15.52%. Both are more frequent in women and at older ages, as well as in people with low levels of education and obesity. The prevalence of hip-osteoarthritis was 5.13%, that of knee-osteoarthritis 13.83%, these are associated with female sex, overweight and obesity. The prevalence of hand osteoarthritis was 7.73%. It is more frequent in women, who are obese, with a low educational level and who are older. Conclusion: The EPISER2016 study is the first to analyse the prevalence of symptomatic osteoarthritis in 5 locations (cervical, lumbar, knee, hip and hands) in Spain. Lumbar spine osteoarthritis is the most prevalent

Biologic Disease-modifying antirheumatic drug attributes in the first lines of treatment of rheumatoid arthritis. 2015 ACORDAR project

Existen pacientes con artritis reumatoide (AR) que no responden de la forma deseada a la terapia biológica. Nuestro objetivo fue reconocer los atributos del FAME biológico (FAMEb) que podrían identificar al más adecuado en las primeras líneas de tratamiento de la AR. Métodos Para reconocer los atributos que podrían definir el FAMEb, se realizó una búsqueda sistemática de la literatura acerca de aspectos generales, farmacología, eficacia, seguridad, administración y coste. A continuación, se realizó un proceso Delphi a 2 rondas entre un grupo de reumatólogos expertos en el manejo de la AR para determinar el grado de acuerdo con los atributos identificados, indicando el grado de importancia que se le daba a cada atributo. Se aplicaron 2 criterios para determinar la consistencia de los resultados: 1) sobre la base de la mediana y el rango intercuartílico, y 2) el cumplimiento simultáneo de media, mediana, desviación estándar, rango intercuartílico y coeficiente de variación. Se determinaron también la concordancia y la ratificación final del panel de expertos. Resultados Ochenta y tres reumatólogos españoles completaron las 2 circulaciones del proceso Delphi. Ninguno de los 77 atributos identificados se consideró de baja importancia, 75 de los 77 (97,4%) se consideraron de alta importancia y 76 de los 77 (98,7%) fueron ratificados. Quince tuvieron el apoyo del 100% del grupo de trabajo. Conclusiones Quince atributos tuvieron el apoyo del 100% del grupo de trabajo y podrían considerarse los que definirían el FAMEb ideal en las primeras líneas de tratamiento de la AR.To date, between 17% and 35% of patients with rheumatoid arthritis (RA) do not respond as expected to the initial biological therapy. The objective of this project is to recognize and weigh the attributes of biologic DMARD (bDMARD) to identify the most appropriate for each case, in the first lines of treatment of RA (after inadequate response to at least one synthetic DMARD or previous bDMARD). Methods To recognize the possible attributes that could define the bDMARD, we performed a systematic search of the literature that recognized the possible attributes involving general aspects, pharmacology, efficacy, safety, management, and cost. Then a Delphi process was conducted with two rounds among a group of selected expert rheumatologists in the management of RA indicating the degree of agreement with the attributes identified in the literature. The project was completed between February and September 2015, indicating the degree of importance that was ascribed to each attribute. Two criteria were applied to determine the consistency of results: 1) based on the median and interquartile range; and 2) on the simultaneous compliance with mean, median, standard deviation, interquartile range and coefficient of variation. The agreement and final ratification of the expert panel were also determined. Results Eighty-three Spanish rheumatologists participated and completed both rounds of the Delphi process. In no case was the importance of the 77 attributes identified considered to be low; 75 of 77 (97.4%) were considered highly important and 76 of 77 (98.7%) were ratified. Fifteen attributes had the support of 100% of the working group. Conclusions There was a high degree of agreement concerning the selected attributes. Fifteen of them had the support of 100% of the working group and could be considered the definition of the ideal bDMARD in the first lines of RA treatment.Sin financiaciónNo data JCR 20180.363 SJR (2018) Q3, 38/66 RheumatologyNo data IDR 2018UE

The prevalence of rheumatoid arthritis in Spain.

Rheumatoid arthritis (RA) prevalence is believed to be around 1% worldwide, although it varies considerably among different populations. The aim of EPISER2016 study was to estimate the prevalence of RA in the general adult population in Spain. We designed a population-based cross-sectional study. A national survey was conducted between November 2016 and October 2017 involving a probabilistic sample from the general population aged 20 years or older. Subjects were randomly selected for phone screening using a computer-assisted telephone interviewer system. Positive RA screening results were evaluated by a rheumatologist. Cases fulfilled the 1987 ACR and/or the 2010 ACR/EULAR criteria; previous diagnosis established by a rheumatologist and clearly identified in medical records were also accepted regardless of the criteria used. Prevalence estimates with 95% CI were calculated taking into account the design of the sample (weighting based on age, sex, and geographic origin using as a reference the distribution of the population in Spain). 4916 subjects participated in the study and 39 RA cases were confirmed. RA estimated prevalence was 0.82% (95% CI 0.59-1.15). Mean age of RA cases was 60.48 (14.85) years, they were more frequently women (61.5%), from urban areas (74.4%), non-smokers (43.6%), and with a high body mass index (53.8% with overweight). Extrapolating to the population in Spain (approximately 37 million are ≥ 20 years old), it was estimated that there were between 220,000 and 430,000 people aged 20 years or older with RA. No undiagnosed cases were detected, which could be related to the establishment of early arthritis clinics around the country, increasing the rates of diagnosis during early phases of RA

Additional file 1: of Role of CXCL13 and CCL20 in the recruitment of B cells to inflammatory foci in chronic arthritis

Table S1. Mean fluorescence intensity and percentage of positive cells for each chemokine receptor on PB and SF from arthritis patients and healthy controls. (DOCX 16 kb

Higher prevalence of psoriatic arthritis in the adult population in Spain? A population-based cross-sectional study.

ObjectiveThe prevalence of psoriatic arthritis (PsA) is very heterogeneous. There are no data on its frequency in the general population in Spain. The aim of EPISER2016 study was to estimate the prevalence of PsA in people aged ≥20 years in Spain.MethodsCross-sectional multicenter population-based study. Subjects from all the autonomous communities in Spain were randomly selected using multistage stratified cluster sampling. Participants in each of the municipalities randomly selected for the study were administered a telephone-based questionnaire to screen for the study diseases. If the participant reported being previously diagnosed, rheumatologists from the participant's reference hospital confirmed the diagnosis based on a review of the clinical history. Subjects not previously diagnosed but whose screening result was positive based on symptoms received a second telephone call from the investigating rheumatologist in order to evaluate the suspicion. If the suspicion remained, an appointment was made at the reference hospital to complete the diagnostic confirmation process according to CASPAR criteria. To calculate the prevalence and its 95% confidence interval (CI), the sample design was taken into account and weighing was calculated considering age, sex and geographic origin.ResultsThe sample comprised 4916 subjects. The prevalence of PsA was 0.58% (95%CI: 0.38-0.87). All but 1 of the 27 cases (96.30%) had been diagnosed prior to EPISER2016.ConclusionThe prevalence of PsA in Spain was among the highest reported to date, only below that reported in Norway (0.67%) and slightly higher than that reported in Italy (0.42%)