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ID PMID Title PublicationDate abstract
31182740 Oral microbial dysbiosis linked to worsened periodontal condition in rheumatoid arthritis 2019 Jun 10 Rheumatoid arthritis (RA) is an autoimmune disease characterized by joint inflammation. Individuals with RA have a higher risk of periodontitis and periodontitis has been linked to RA through the production of enzymes by periodontal pathogens that citrullinate proteins. This linkage is supported by findings that periodontitis is associated with increased RA severity and treatment of periodontitis can improve the symptoms of RA. The possible mechanism for this association is through dysbiosis of the oral microbiota triggered by RA-induced systemic inflammation. We examined the RA status of subjects by measuring the number of tender and swollen joints, anti-citrullinated protein antibody and rheumatoid factor. Periodontal disease status and salivary cytokine levels were measured, and dental plaque analyzed by 16S rRNA high throughput sequencing. RA patients had a higher bacterial load, a more diverse microbiota, an increase in bacterial species associated with periodontal disease, more clinical attachment loss, and increased production of inflammatory mediators including IL-17, IL-2, TNF, and IFN-γ. Furthermore, changes in the oral microbiota were linked to worse RA conditions. Our study provides new insights into the bi-directional relationship between periodontitis and RA and suggest that monitoring the periodontal health of RA patients is particularly important.
30394138 Upadacitinib for the treatment of rheumatoid arthritis. 2019 Jan Introduction: Tofacitinib and baricitinib have recently been approved as second-line treatments for Rheumatoid arthritis (RA) though their maximum expected efficacy may be limited by dose-related toxicities. Upadacitinib selectively inhibits Janus Kinase 1 (JAK1) which could potentially reduce JAK2 and JAK3-related side effects. Areas covered: In this paper, we review a newly developed oral selective JAK inhibitor, upadacitinib for the treatment of RA. The doses of upadacitinib extended-release 15 and 30 mg daily selected in phase III RA studies have shown a near-maximum efficacy in phase II studies. Upadacitinib inhibited radiographic progression and displayed rapid and sustained clinical and functional efficacy in RA when in combination with methotrexate (MTX), upadacitinib was superior to placebo in MTX-Inadequate Responders (IRs) and biologic disease modifying antirheumatic drugs-IRs while as monotherapy, it was superior to MTX in MTX-IRs and MTX-naïve patients. Upadacitinib was superior to adalimumab using ACR70, reduction of pain-VAS and improvement of HAQ-DI. The comparison with abatacept is still ongoing. Expert commentary: Upadacitinib has displayed a rapid and favorable efficacy profile in RA but despite being a selective JAK1 inhibitor appears to have a similar safety profile to less-selective Jakinibs. Longer term safety data are awaited.
30321331 An Increased Abundance of Clostridiaceae Characterizes Arthritis in Inflammatory Bowel Dis 2019 Apr 11 BACKGROUND: Inflammatory bowel diseases (IBDs) are a group of heterogeneous inflammatory conditions affecting the gastrointestinal tract. Although there is considerable evidence linking the gut microbiota to intestinal inflammation, there is limited knowledge on its potential role in the development of extraintestinal manifestations of IBD. METHODS: Four groups of patients were included: IBD-associated arthropathy (IBD-A); IBD without arthropathy (IBD-N); rheumatoid arthritis (RA); and non-IBD, nonarthritis controls. DNA from stool samples was isolated and sequenced using the Illumina platform. Paired-end reads were quality-controlled using SHI7 and processed with SHOGUN. Abundance and diversity analyses were performed using QIIME, and compositional biomarker identification was performed using LEfSe. RESULTS: One hundred eighty patients were included in the analysis. IBD-A was associated with an increased abundance of microbial tyrosine degradation pathways when compared with IBD-N (P = 0.02), whereas IBD-A and RA patients both shared an increased abundance of Clostridiaceae when compared with controls (P = 0.045). We found that history of bowel surgery was a significant source of variability (P = 0.001) among all IBD patients and was associated with decreased alpha diversity and increased abundance of Enterobacteriaceae (P = 0.004). CONCLUSIONS: An increased abundance of gut microbial tyrosine degradation pathways was associated with IBD-A. An increased abundance of Clostridiaceae was shared by both IBD-A and RA patients and suggests a potentially common microbial link for inflammatory arthritis. The increased abundance of Enterobacteriaceae, previously reported in IBD, may be due to the effects of previous bowel surgery and highlights the importance of controlling for this variable in future studies.
31369868 Factors influencing the choice of biologic therapy following Rituximab in patients with rh 2020 Jan OBJECTIVES: To assess factors influencing the choice and effectiveness of biological disease-modifying antirheumatic drugs (DMARDs) following failure of rituximab (RTX) in rheumatoid arthritis (RA), taking patient profile into account. METHODS: In a retrospective, multicenter study, data about RA patients starting a new biologic during the year after RTX discontinuation were collected at baseline (when the biologic was introduced after RTX), and during follow-up (3, 6, and 12 months). Characteristics of patients receiving tocilizumab (TCZ), abatacept (ABA), or a TNFα inhibitor (TNFi), EULAR response, and retention rate were compared using multidimensional factorial analysis for patient profiles and multivariate analysis including propensity score built on the patient profile. RESULTS: Among 152 patients analyzed (37.5% TCZ, 31.6% ABA, 30.9% TNFi), sex, disease characteristics and activity, concomitant DMARDs or glucocorticoids, and previous use of RTX and TNFi were similar at baseline. Patients receiving ABA were slightly older. Multimorbidity index was higher but not significantly different. Multidimensional factorial analysis showed a distinct profile of patients receiving ABA, characterized by older age, more men, more smokers, more comorbidities, and higher anti-cyclic citrullinated peptide antibody. At 1 year, drug retention was higher for ABA than TNFi after adjustment for disease duration, concomitant DMARDs, glucocorticoids, and propensity score (P=0.04). Tolerance and serious infections were similar among groups. CONCLUSIONS: The profile of patients receiving ABA following failure of RTX differed from TNFi and TCZ using multidimensional factorial analysis. After adjustment for propensity score, drug retention rate remained higher with ABA than TNFi.
30737711 A Flexible Open-Source Decision Model for Value Assessment of Biologic Treatment for Rheum 2019 Jun OBJECTIVE: The nature of model-based cost-effectiveness analysis can lead to disputes in the scientific community. We propose an iterative and collaborative approach to model development by presenting a flexible open-source simulation model for rheumatoid arthritis (RA), accessible to both technical and non-technical end-users. METHODS: The RA model is a discrete-time individual patient simulation with 6-month cycles. Model input parameters were estimated based on currently available evidence and treatment effects were obtained with Bayesian network meta-analysis techniques. The model contains 384 possible model structures informed by previously published models. The model consists of the following components: (i) modifiable R and C++ source code available in a GitHub repository; (ii) an R package to run the model for custom analyses; (iii) detailed model documentation; (iv) a web-based user interface for full control over the model without the need to be well-versed in the programming languages; and (v) a general audience web-application allowing those who are not experts in modeling or health economics to interact with the model and contribute to value assessment discussions. RESULTS: A primary function of the initial version of RA model is to help understand and quantify the impact of parameter uncertainty (with probabilistic sensitivity analysis), structural uncertainty (with multiple competing model structures), the decision framework (cost-effectiveness analysis or multi-criteria decision analysis), and perspective (healthcare or limited societal) on estimates of value. CONCLUSION: In order for a decision model to remain relevant over time it needs to evolve along with its supporting body of clinical evidence and scientific insight. Multiple clinical and methodological experts can modify or contribute to the RA model at any time due to its open-source nature.
30260261 Smoking and response to rituximab in rheumatoid arthritis: results from an international E 2019 Jan OBJECTIVES: To investigate whether smoking habits predict response to rituximab (RTX) in rheumatoid arthritis (RA). METHOD: We included patients from the CERERRA international cohort receiving the first treatment cycle with available smoking status (n = 2481, smokers n = 528, non-current smokers n = 1953) and at least one follow-up visit. Outcome measures were change in Disease Activity Score based on 28-joint count (ΔDAS28) and European League Against Rheumatism (EULAR) good response at 6 months, with non-current smokers as the referent group. RESULTS: Compared with non-smokers at baseline, smokers were more often rheumatoid factor (RF)/anti-citrullinated protein antibody (ACPA) positive and males, had shorter disease duration, lower DAS28 and Health Assessment Questionnaire (HAQ) score, a higher number of prior biological disease-modifying anti-rheumatic drugs, and were more likely to receive concomitant conventional synthetic disease-modifying anti-rheumatic drug (csDMARDs). Disease activity had decreased less in smokers at 6 months (ΔDAS28 = 1.5 vs 1.7, p = 0.006), although the difference was no longer significant after correction for baseline DAS28 (p = 0.41). EULAR good response rates did not differ between smokers and non-smokers overall or stratified by RF/ACPA status, although smokers had lower good response rates among seronegative patients (ACPA-negative: 6% vs 14%, RF-negative: 11% vs 18%). Smoking did not predict good response [odds ratio (OR) = 1.04, 95% confidence interval (CI) = 0.76-1.41], while ACPA, DAS28, HAQ, and concomitant csDMARDs were significant predictors for good response. However, when stratified by country, smokers were less likely to achieve good response in Sweden (unadjusted OR = 0.24, 95% CI = 0.07-0.89), and a trend was seen in the Czech Republic (OR = 0.45, 95% CI = 0.16-1.02). CONCLUSION: In this large, observational, multinational RA cohort, smokers starting RTX differed from non-smokers by having shorter disease duration and lower disease activity, but more previous treatments. The overall results do not support smoking as an important predictor for response to RTX in patients with RA.
31001653 [Tight control-Demand for short term control of rheumatoid arthritis]. 2019 Jun The prognosis of rheumatoid arthritis (RA) has been significantly improved in recent decades. This is mainly due to earlier detection, better diagnostics and new treatment options, such as the optimized use of classical disease-modifying antirheumatic drugs (DMARD) and biologicals. Other factors involved were earlier intervention, improved availability of information and analyses and certainly also standardization of care (e.g. guidelines). An additional important component is close monitoring of disease activity in order to be able to adapt the treatment in a timely manner and thus prevent damage. The demand for tight control is the subject of this article.
31178673 Differentially expressed genes between systemic sclerosis and rheumatoid arthritis. 2019 BACKGROUND: Evidence is accumulating to characterise the key differences between systemic sclerosis (SSc) and rheumatoid arthritis (RA), which are similar but distinct systemic autoimmune diseases. However, the differences at the genetic level are not yet clear. Therefore, the aim of the present study was to identify key differential genes between patients with SSc and RA. METHODS: The Gene Expression Omnibus database was used to identify differentially expressed genes (DEGs) between SSc and RA biopsies. The DEGs were then functionally annotated using Gene Ontology (GO) terms and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways with the Database for Annotation, Visualization and Integrated Discovery (DAVID) tools. A protein-protein interaction (PPI) network was constructed with Cytoscape software. The Molecular Complex Detection (MCODE) plugin was also used to evaluate the biological importance of the constructed gene modules. RESULTS: A total of 13,556 DEGs were identified between the five SSc patients and seven RA patients, including 13,465 up-regulated genes and 91 down-regulated genes. Interestingly, the most significantly enriched GO terms of up- and down-regulated genes were related to extracellular involvement and immune activity, respectively, and the top six highly enriched KEGG pathways were related to the same processes. In the PPI network, the top 10 hub nodes and top four modules harboured the most relevant genes contributing to the differences between SSc and RA, including key genes such as IL6, EGF, JUN, FGF2, BMP2, FOS, BMP4, LRRK2, CTNNB1, EP300, CD79, and CXCL13. CONCLUSIONS: These genes such as IL6, EGF, JUN, FGF2, BMP2, FOS, BMP4, LRRK2, CTNNB1, EP300, CD79, and CXCL13 can serve as new targets for focused research on the distinct molecular pathogenesis of SSc and RA. Furthermore, these genes could serve as potential biomarkers for differential diagnoses or therapeutic targets for treatment.
31275607 Screening for and management of comorbidities after a nurse-led program: results of a 3-ye 2019 BACKGROUND/PURPOSE: Cardiovascular (CV) risk, cancer, infections and osteoporosis should be screened for in rheumatoid arthritis (RA). The objective was to assess 3-year effects of a nurse visit for comorbidity counselling. METHODS: This was an open long-term (3 years) extension of the Comorbidities and Education in Rheumatoid Arthritis 6-month randomised controlled trial in which patients with definite, stable RA were visiting a nurse for comorbidity counselling. Comorbidity status was assessed and nurses provided advice on screening and management, at baseline and 3 years later. A score was developed to quantify comorbidity screening and management: 0-100, where lower scores indicate better screening and management. The score was compared between baseline and 3-year assessment using a Wilcoxon test for paired data. RESULTS: Of the 970 recruited patients, 776 (80%) were followed-up at 2-4 years and 769 (79%) had available data for comorbidities at both time points: mean (±SD) age 58 (±11) years and mean disease duration 14 (±10) years; 614 (80%) were women, the mean Disease Activity Score 28 was 3.0±1.3, and 538 (70%) were receiving a biologic. At baseline, the mean comorbidity screening score was 36.6 (±19.9) and it improved at 3 years to 24.3 (±17.8) (p<0.0001), thus with a relative improvement of 33% (improvement of 12 points). CV risk screening, vaccination status and bone densitometry performance improved the most. CONCLUSIONS: Comorbidity screening was suboptimal but improved notably over 3 years, after a nurse-led programme aiming at checking systematically for comorbidity screening and giving patient advice. This long-term efficacy pleads in favour of nurse-led interventions to better address comorbidities in RA. TRIAL REGISTRATION NUMBER: NCT01315652.
31242798 14-3-3η Protein in serum and synovial fluid correlates with radiographic damage and progr 2020 Jul Objectives: The aim of the study is to examine the association between 14-3-3η protein levels in both serum and synovial fluid (SF) with various parameters in a longitudinal cohort of patients with established rheumatoid arthritis (RA).Methods: Serum and SF samples were obtained from RA patients and 14-3-3η levels were measured. Radiological damage and progression were evaluated using Sharp/van der Heijde score (SHS) at study entry and at 2-years follow-up.Results: A total of 39 RA patients were included with a mean disease duration of 9.6 ± 8 years. Levels of 14-3-3η were two-fold higher in SF than in serum (mean of 3.7 versus 1.7 ng/mL, respectively). While no significant association was found between 14-3-3η levels with disease activity or other laboratory assessments, both serum and SF 14-3-3η levels positively correlated with radiographic damage at baseline (SHS; p < .001). SF, but not serum, 14-3-3η levels correlated with absolute progression (p < .03).Conclusion: 14-3-3η levels are significantly higher in RA SF than in serum in an established RA cohort. Serum and SF 14-3-3η levels correlate with radiographic damage at baseline and at 2-years follow-up. This study further substantiates the utility of 14-3-3η as a biomarker for mechanistic joint damage in established RA.
31354718 Computational Methodologies for the in vitro and in situ Quantification of Neutrophil Extr 2019 Neutrophil extracellular traps (NETs) are a neutrophil defensive mechanism where chromatin is expelled together with antimicrobial proteins in response to a number of stimuli. Even though beneficial in many cases, their dysfunction has been implicated in many diseases, such as rheumatoid arthritis and cancer. Accurate quantification of NETs is of utmost importance for correctly studying their role in various diseases, especially when considering them as therapeutic targets. Unfortunately, NET quantification has a number of limitations. However, recent developments in computational methodologies for quantifying NETs have vastly improved the ability to study NETs. Methods range from using ImageJ to user friendly applications and to more sophisticated machine-learning approaches. These various methods are reviewed and discussed in this review.
31182152 The activin-follistatin anti-inflammatory cycle is deregulated in synovial fibroblasts. 2019 Jun 10 BACKGROUND: Activin A and follistatin exhibit immunomodulatory functions, thus affecting autoinflammatory processes as found in rheumatoid arthritis (RA). The impact of both proteins on the behavior of synovial fibroblasts (SF) in RA as well as in osteoarthritis (OA) is unknown. METHODS: Immunohistochemical analyses of synovial tissue for expression of activin A and follistatin were performed. The influence of RASF overexpressing activin A on cartilage invasion in a SCID mouse model was examined. RASF and OASF were stimulated with either IL-1β or TNFα in combination with or solely with activin A, activin AB, or follistatin. Protein secretion was measured by ELISA and mRNA expression by RT-PCR. Smad signaling was confirmed by western blot. RESULTS: In human RA synovial tissue, the number of activin A-positive cells as well as its extracellular presence was higher than in the OA synovium. Single cells within the tissue expressed follistatin in RA and OA synovial tissue. In the SCID mouse model, activin A overexpression reduced RASF invasion. In human RASF, activin A was induced by IL-1β and TNFα. Activin A slightly increased IL-6 release by unstimulated RASF, but decreased protein and mRNA levels of follistatin. CONCLUSION: The observed decrease of cartilage invasion by RASF overexpressing activin A in the SCID mouse model appears to be mediated by an interaction between activin/follistatin and other local cells indirectly affecting RASF because activin A displayed certain pro-inflammatory effects on RASF. Activin A even inhibits production and release of follistatin in RASF and therefore prevents itself from being blocked by its inhibitory binding protein follistatin in the local inflammatory joint environment.
31787604 Pain and Self-reported Swollen Joints Are Main Drivers of Patient-reported Flares in Rheum 2020 Sep 1 OBJECTIVE: To examine prospectively self-reported flare characteristics and their longitudinal association with disease activity and patient-reported outcomes (PRO) in patients with rheumatoid arthritis (RA). METHODS: Consecutive RA patients with 28-joint count Disease Activity Score based on C-reactive protein (DAS28-CRP) < 3.2 and no swollen joints were examined at baseline, Month 6, and Month 12. Assessments included joint counts, DAS28-CRP, visual analog scale-evaluator's global assessment (EGA), and PRO. Every third month, patients completed the Flare Assessment in Rheumatoid Arthritis and RA Flare Questionnaire, and disclosed self-management strategies. Flaring and non-flaring patients were compared and longitudinal associations between self-reported flare status (yes/no) and disease activity, PRO, and treatment escalation were explored. RESULTS: Among 80 patients with RA [74% females, mean (SD) age 63 (10) yrs, disease duration 11 (7) yrs, and baseline DAS28-CRP 1.9 (0.6)], 64 (80%) reported flare at least once during 12 months. Fifty-five percent of flares lasted less than 1 week. Common self-management strategies were analgesics (50%) and restricted activities (38%). Patients who reported being in flare had consistently higher disease activity measures and PRO compared to patients without flare. In a partly adjusted model, all flare domains, patient-reported swollen and tender joint counts and disease activity measures were associated with flares. In fully adjusted analyses, present flare was independently associated with pain (OR 1.85, 95% CI 1.34-2.60), patient-reported swollen joints (OR 1.18, 95% CI 1.03-1.36), and higher EGA (OR 1.15, 95% CI 1.04-1.28). Treatment escalation was associated with present flare (p ≤ 0.001). CONCLUSION: In RA, self-reported flares were frequent, mainly managed by analgesics, substantiated by higher disease activity measures, independently associated with pain and patient-reported swollen joints, and related to treatment escalation.
30630495 Common mechanisms and holistic care in atherosclerosis and osteoporosis. 2019 Jan 10 Cardiovascular (CV) disease and osteoporosis (OP) have become increasing challenges in the aging population and even more in patients with inflammatory rheumatic diseases, such as rheumatoid arthritis, spondyloarthropathies, and systemic lupus erythematosus. In this review, we discuss how the epidemiology and pathogenesis of CV events and OP are overlapping. Smoking, diabetes mellitus, physical inactivity as conventional risk factors as well as systemic inflammation are among the modifiable risk factors for both CV events and bone loss. In rheumatic patients, systemic "high-grade" inflammation may be the primary driver of accelerated atherogenesis and bone resorption. In the general population, in which some individuals might have low-grade systemic inflammation, a holistic approach to drug treatment and lifestyle modifications may have beneficial effects on the bone as well as the vasculature. In rheumatic patients with accelerated inflammatory atherosclerosis and bone loss, the rapid and effective suppression of inflammation in a treat-to-target regime, aiming at clinical remission, is necessary to effectively control comorbidities.
31280933 Predicting drug-free remission in rheumatoid arthritis: A prospective interventional cohor 2019 Dec BACKGROUND: Many patients with rheumatoid arthritis (RA) achieve disease remission with modern treatment strategies. However, having achieved this state, there are no tests that predict when withdrawal of therapy will result in drug-free remission rather than flare. We aimed to identify predictors of drug-free remission in RA. METHODS: The Biomarkers of Remission in Rheumatoid Arthritis (BioRRA) Study was a unique, prospective, interventional cohort study of complete and abrupt cessation of conventional synthetic disease-modifying anti-rheumatic drugs (DMARDs). Patients with RA of at least 12 months duration and in clinical and ultrasound remission discontinued DMARDs and were monitored for six months. The primary outcome was time-to-flare, defined as disease activity score in 28 joints with C-reactive protein (DAS28-CRP) ≥ 2.4. Baseline clinical and ultrasound measures, circulating inflammatory biomarkers, and peripheral CD4(+) T cell gene expression were assessed for their ability to predict time-to-flare and flare/remission status by Cox regression and receiver-operating characteristic (ROC) analysis respectively. RESULTS: 23/44 (52%) eligible patients experienced an arthritis flare after a median (IQR) of 48 (31.5-86.5) days following DMARD cessation. A composite score incorporating five baseline variables (three transcripts [FAM102B, ENSG00000228010, ENSG00000227070], one cytokine [interleukin-27], one clinical [Boolean remission]) differentiated future flare from drug-free remission with an area under the ROC curve of 0.96 (95% CI 0.91-1.00), sensitivity 0.91 (0.78-1.00) and specificity 0.95 (0.84-1.00). CONCLUSION: We provide proof-of-concept evidence for predictors of drug-free remission in RA. If validated, these biomarkers could help to personalize immunosuppressant withdrawal: a therapy paradigm shift with ensuing patient and economic benefits.
31594453 Non-coding RNAs - A primer for the laboratory scientist. 2019 Oct Advances in molecular genetics have identified several species of RNA that fail to translate - hence the non-coding RNAs. The two major groups within this class of nucleic acids are microRNAs (miRNA) and long non-coding RNAs (lncRNA). There is growing body of evidence supporting the view that these molecules have regulatory effect on both DNA and RNA. The objective of this brief review is to explain the molecular genetic of these molecules, to summarize their potential as mediators of disease, and to highlight their value as diagnostic markers and as tools in disease management.
31161840 Impact of IL12B Polymorphisms on Genetic Susceptibility and IL-12p40 and IL-23 Serum Level 2020 Feb The aim of this study was to evaluate the possible association of IL12B gene polymorphisms with serum levels of IL-12p40, IL-23 and genetic susceptibility to rheumatoid arthritis (RA) in the Bulgarian population. Genotyping for IL12Bpro (rs17860508) and IL12B A/C - 3' UTR (rs3212227) polymorphisms was performed by polymerase chain reaction (PCR)-based methods in 125 RA patients and 239 healthy controls. The IL-23 and IL-12p40 serum levels were measured by enzyme-linked immunosorbent assay (ELISA). An association was established between the rs17860508 polymorphism and RA susceptibility in Bulgarian population with an increased frequency of rs17860508 minor allele-2 and homozygous genotype-22 in RA patients. The rs17860508 risk RA genotype-22 was also significantly correlated to elevated serum IL-23 in RA patients. Although, there was no association between the rs3212227 and genetic predisposition to RA, significantly increased serum levels of both Il-12p40 and IL-23 were observed in RA patients with the rs3212227 AA genotype. Furthermore, the distribution of haplotypes and genotype combination in our cohort indicated increased RA risk in individuals carrying the rs17860508/rs3212227 2/A haplotype or 2.2/AC+CC combination, while 1/A haplotype or 1.1/AA combination may be protective for RA. In conclusion, our study demonstrates a functional effect of IL12B polymorphisms on IL-12p40 and IL-23 cytokine levels in RA patients and suggests a leading role for IL12B rs17860508 in the genetic predisposition to RA, while IL12B rs3212227 significantly modify the RA risk in Bulgarian population.
31074725 Progranulin-autoantibodies in sera of rheumatoid arthritis patients negative for rheumatoi 2020 Jan OBJECTIVES: Previously we discovered antibodies against progranulin (PGRN-abs) in a protein array-based screening of sera from various rheumatic diseases. Here we conducted a study to evaluate the prevalence of PGRN-abs in seropositive and seronegative rheumatoid arthritis (RA). METHODS: PGRN-abs were determined in the sera from 257 RA patients being seropositive for RF-IgM and/or ACPA-IgG and from 224 seronegative RA patients who were prospectively included in this study (total RA cohort n=481). All serum samples from the included participants were tested for RF-IgM as well as for ACPA-IgG, and PGRN-abs were determined using a previously described ELISA. Statistics was performed using the χ2 test for evaluating differences in clinical data; to evaluate independent statistical effects on the frequency of PGRN-abs status a logistic regression model with Wald-test was performed. RESULTS: PGRN-abs were detected in 25.3% from seropositive RA and in 21.0% from RF- and ACPA-negative RA resulting in a prevalence of 23.7% for both cohorts together. Comparing mean DAS28 values in the PGRN-abs positive cohort with the PGRN-abs negative cohort, the DAS28 value was significantly higher in PGRN-abs positive RA patients (3.81 vs. 3.50, p=0.038). A trend for higher frequencies of PGRN-abs in sera of RA patients with unfavourable characteristics such as erosive disease or requiring TNFi medication was observed. CONCLUSIONS: These data suggest that the determination of PGRN-abs in seronegative RA patients may reduce their seronegative status. Further studies are required to evaluate PGRN-abs as a potential diagnostic marker in RA.
31229943 Frequency and clinical relevance of anti-cyclic citrullinated peptide antibody in idiopath 2019 Jul RATIONALE: Although anti-cyclic citrullinated peptide antibody (ACPA) is highly specific for rheumatoid arthritis (RA), some patients with idiopathic interstitial pneumonia (IIP) are ACPA-positive, but do not fulfill the diagnostic criteria for RA. The clinical significance of ACPA in such patients is as yet unclear. OBJECTIVE: We aimed to investigate the frequency of ACPA positivity and its clinical significance in patients initially diagnosed with IIP. METHODS: We retrospectively analyzed 370 consecutive patients who were diagnosed with IIP and for whom serum ACPA results were available. The incidence of ACPA positivity and its predictive role for subsequent onset of RA was examined. Risk factors for development of RA were evaluated by Cox hazards analysis. RESULTS: Of 370 patients, 24 (6.5%) were ACPA-positive, including 7 of 144 patients (4.9%) initially diagnosed with idiopathic pulmonary fibrosis (IPF) and 17 of 226 patients (7.5%) with non-IPF. The cumulative 3-year incidence of overt RA was significantly higher in patients who were positive rather than negative for ACPA (28.9% vs. 1.1%, P < 0.01). On multivariate analysis, younger age was independently associated with development of RA in patients who were ACPA-positive (per one year increase: hazard ratio = 0.93, 95% confidence interval 0.87-0.99, P = 0.03). CONCLUSION: Among patients initially diagnosed with IIP, a small proportion was positive for ACPA, of whom approximately one-third subsequently developed RA within 3 years from IIP diagnosis. Clinicians should be alert to the possibility of RA developing in patients with IIP who are ACPA-positive, particularly those patients who are younger.
30760471 Prevotella copri in individuals at risk for rheumatoid arthritis. 2019 May OBJECTIVES: Rheumatoid arthritis (RA) has been associated with a relative expansion of faecal Prevotellaceae. To determine the microbiome composition and prevalence of Prevotella spp. in a group of individuals at increased risk for RA, but prior to the development of the disease. METHODS: In an ongoing cohort study of first-degree relatives (FDRs) of patients with RA, we identified 'FDR controls', asymptomatic and without autoantibodies, and individuals in pre-clinical RA stages, who had either developed anticitrullinated peptide antibodies or rheumatoid factor positivity and/or symptoms and signs associated with possible RA. Stool sampling and culture-independent microbiota analyses were performed followed by descriptive statistics and statistical analyses of community structures. RESULTS: A total of 133 participants were included, of which 50 were categorised as 'FDR controls' and 83 in 'pre-clinical RA stages'. The microbiota of individuals in 'pre-clinical RA stages' was significantly altered compared with FDR controls. We found a significant enrichment of the bacterial family Prevotellaceae, particularly Prevotella spp., in the 'pre-clinical RA' group (p=0.04). CONCLUSIONS: Prevotella spp. enrichment in individuals in pre-clinical stages of RA, before the onset of RA, suggests a role of intestinal dysbiosis in the development of RA.