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ID PMID Title PublicationDate abstract
26708444 Evaluation of switching from intravenous to subcutaneous formulation of tocilizumab in pat 2016 Sep OBJECTIVE: To evaluate the efficacy of switching the route from intravenous tocilizumab (TCZ) infusion (TCZ-IV) to subcutaneous TCZ injection (TCZ-SC) in a real-world setting through a comparison of the clinical response. METHODS: Fifty-eight rheumatoid arthritis (RA) patients, for whom TCZ-SC was initiated following TCZ-IV between June 2013 and August 2014, were consecutively enrolled. Disease activity score (DAS)28-ESR, simplified disease activity index (SDAI), and clinical disease activity index (CDAI) were examined at baseline and after switching from TCZ-IV to TCZ-SC for 3 months. We investigated whether body weight and body mass index (BMI) affected the efficacy of TCZ-SC. RESULTS: Most of the patients had achieved remission or low disease activity at baseline (77.6% examined by DAS28). Fifty-seven patients (98%) continued the TCZ-SC treatment, and the disease activity was well controlled after 3 months. ΔDAS28 tended to be worsened after switching to TCZ-SC in the high-body-weight groups (≥60 kg) as compared with the groups with body weight <60 kg, although no statistical significance was found. BMI did not affect the efficacy of TCZ-SC. CONCLUSIONS: Caution should be exercised in the high-body-weight subjects, but these data indicate that TCZ-SC maintains the favorable RA disease activity established using TCZ-IV.
26239524 Post-Traumatic Stress Disorder and Risk for Incident Rheumatoid Arthritis. 2016 Mar OBJECTIVE: To examine the association between symptoms of post-traumatic stress disorder (PTSD) and rheumatoid arthritis (RA) risk in a prospective cohort and to characterize the role of smoking in this relationship. METHODS: A subset (n = 54,224) of the Nurses' Health Study II, a prospective cohort of female nurses, completed the Brief Trauma Questionnaire and a screen for PTSD symptoms. Participants were categorized based on trauma exposure and number of PTSD symptoms. Incident RA cases (n = 239) from 1989 to 2011 were identified. Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (95% CIs) between PTSD symptoms and incident RA. To identify the impact of smoking, secondary and subgroup analyses were performed. In all analyses, PTSD and smoking were lagged 2 years before the development of RA. RESULTS: Compared to no history of trauma/PTSD symptoms, the HR for ≥4 PTSD symptoms and incident RA was 1.76 (95% CI 1.16-2.67) in models adjusted for age, race, and socioeconomic status. The risk for RA increased with an increasing number of PTSD symptoms (P = 0.01). When smoking was added to the model, the HR for RA remained elevated (HR 1.60 [95% CI 1.05-2.43]). In a subgroup analysis, excluding women who smoked before PTSD onset, results were unchanged (HR 1.68 [95% CI 1.04-2.70]). CONCLUSION: This study suggests that women with high PTSD symptomatology have an elevated risk for RA, independent of smoking, adding to emerging evidence that stress is an important determinant of physical health.
27629845 The Activity of JAK/STAT and NF-κB in Patients with Rheumatoid Arthritis. 2016 Jul BACKGROUND: Research is still being conducted in order to determine the mechanisms responsible for the initiation of rheumatoid arthritis (RA) as well as for its persistence and progression. OBJECTIVES: The aim of this work was to establish the expression of the signal transducer and activator of transcription (STAT) transcription factors and the nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) transcription factor in peripheral blood leukocytes and synovial fluid cells. The correlations between the activation level of the transcription factors and the activity of the disease were also analyzed. MATERIAL AND METHODS: In total, the study included 34 RA patients and 19 healthy individuals as controls. The expression of NFκB, STAT1, STAT3, STAT4, STAT5 and STAT6 in peripheral blood leukocytes and synovial fluid cells was established. The immunocytochemistry method was used to determine the degree of activation of STAT and NF-κB transcription factors. For the location of the factors, primary polyclonal anti-STATs and monoclonal anti-NF-κB antibodies were used. RESULTS: The expression of STAT1, STAT3, STAT4, STAT5, STAT6 and NFκB was significantly higher in the group of RA patients than in the controls. No statistically significant differences were found between the expression of STATs in peripheral blood leukocytes and synovial fluid cells. CONCLUSIONS: In comparison with the control group, the expression of the STAT and NFκB transcription factors in RA patients was higher, which may be helpful in better understanding the etiopathogenesis of the disease in the future, and may potentially have important therapeutic implications.
26209657 Crystal structure of Porphyromonas gingivalis peptidylarginine deiminase: implications for 2016 Jun BACKGROUND: Periodontitis (PD) is a known risk factor for rheumatoid arthritis (RA) and there is increasing evidence that the link between the two diseases is due to citrullination by the unique bacterial peptidylarginine deiminase (PAD) enzyme expressed by periodontal pathogen Pophyromonas gingivalis (PPAD). However, the precise mechanism by which PPAD could generate potentially immunogenic peptides has remained controversial due to lack of information about the structural and catalytic mechanisms of the enzyme. OBJECTIVES: By solving the 3D structure of PPAD we aim to characterise activity and elucidate potential mechanisms involved in breach of tolerance to citrullinated proteins in RA. METHODS: PPAD and a catalytically inactive mutant PPAD(C351A) were crystallised and their 3D structures solved. Key residues identified from 3D structures were examined by mutations. Fibrinogen and α-enolase were incubated with PPAD and P. gingivalis arginine gingipain (RgpB) and citrullinated peptides formed were sequenced and quantified by mass spectrometry. RESULTS: Here, we solve the crystal structure of a truncated, highly active form of PPAD. We confirm catalysis is mediated by the following residues: Asp130, His236, Asp238, Asn297 and Cys351 and show Arg152 and Arg154 may determine the substrate specificity of PPAD for C-terminal arginines. We demonstrate the formation of 37 C-terminally citrullinated peptides from fibrinogen and 11 from α-enolase following incubation with tPPAD and RgpB. CONCLUSIONS: PPAD displays an unequivocal specificity for C-terminal arginine residues and readily citrullinates peptides from key RA autoantigens. The formation of these novel citrullinated peptides may be involved in breach of tolerance to citrullinated proteins in RA.
26481605 Characteristics of traditional Chinese medicine use in patients with rheumatoid arthritis 2015 Dec 24 ETHNOPHARMACOLOGICAL RELEVANCE: Large-scale study of traditional Chinese medicine (TCM) usage among patients with rheumatoid arthritis (RA) is lacking. The aim of this study is to evaluate the TCM usage among RA patients in Taiwan. MATERIALS AND METHODS: We examined the "registry for catastrophic illness patient dataset" of the National Health Insurance Research Database (NHIRD; n=23 million people) in Taiwan. Patients (n=25,263) newly diagnosed as RA in 2001-2009 were included and then followed-up until the end of 2011. Based on the medical utilization, they were further categorized into TCM users (n= 6891; 27.3%) and non-TCM users (n=18,372; 72.7%). The demographic data and core prescription patterns of the TCM users were analyzed. RESULTS: Compared to non-TCM user, TCM users were younger (mean age: 49.6 versus 54.0 years), had a higher female/male ratio (82.7%/17.3% versus 74.1%/25.9%), resided in more urbanized area. Herbal remedies were the most commonly used therapeutic approach (76.4%), followed by combining acupuncture (21.1%). The frequency of outpatient visits in TCM users was higher across all disease categories except circulatory system. The most commonly prescribed formula and herb was Shang-Jong-Shiah-Tong-Yong-Tong-Feng-Wan and Rhizoma Corydalis, respectively. The analysis of core pattern revealed that Dang-Gui-Nian-Tong-Tang, Shu-Jing-Huo-Xie-Tang, Gui-Zhi-Shao-Yao-Zhi-Mu-Tang, Myrrha and Olibanum, were among the most frequently used combinations. RA patients who had anxiety and depression, allergic rhinitis, osteoporosis, menstrual disorder, and menopausal syndrome were prone to have more TCM visits compared to non-TCM users. CONCLUSIONS: Our population-based study revealed the high prevalence and specific usage patterns of TCM in the RA patients in Taiwan. The information could be used for further pharmacological investigation and clinical trials.
27595364 Follicular helper T cells in peripheral blood of patients with rheumatoid arthritis. 2017 Nov INTRODUCTION: Rheumatoid arthritis (RA) is a chronic autoimmune disease that is characterized by the presence of different autoantibodies such as rheumatoid factor (RF) and anti-citrullinated protein antibodies. CD4T cells expressing CXCR5, referred as follicular helper T cells (Tfh), collaborate with B cells to produce antibodies. Differential expression of CXCR3 and CCR6 within CD4(+)CXCR5(+) T cells defines three mayor subsets: CXCR3(+)CCR6(-) (Tfh1), CXCR3(-)CCR6(-) (Tfh2) and CXCR3(-)CCR6(+) (Tfh17). The aim of the study was to assess whether there is an association between the percentage of these cells and RA and whether there is a correlation with disease activity. MATERIAL AND METHODS: Twenty-four RA patients, 22 healthy controls (HC) and 16 undifferentiated arthritis (UA) patients were included. Percentage of CD4(+)CXCR5(+) T cells and their subsets were analyzed by flow cytometry. RESULTS: No differences were found in the percentages of CD4(+)CXCR5(+) T cells in the comparison of RA vs HC or RA vs UA patients. Tfh1, Tfh2 and Tfh17 subsets showed no differences either. There was no correlation between CD4(+)CXCR5(+)T cells, Tfh1, Tfh2 and Tfh17, and Disease Activity Score in twenty-eight joints (DAS28) or erythrocyte sedimentation rate. Surprisingly, there was a positive correlation between Tfh17 cells and C-reactive protein. Finally, there was no correlation between CD4(+)CXCR5(+) T cells, or their subsets, and anti-mutated citrullinated vimentin, or between the cells and RF. CONCLUSION: There were no differences between the percentages of CD4(+)CXCR5(+) T cells and their subsets in peripheral blood of RA patients and the percentages of cells in the control groups. This finding does not rule out a pathogenic role of these cells in the development and activity of RA.
26017221 Inhibition of Inflammation and Bone Erosion by RNA Interference-Mediated Silencing of Hete 2015 Sep OBJECTIVE: The nuclear protein heterogeneous nuclear RNP A2/B1 (hnRNP A2/B1) is involved in posttranscriptional regulation of gene expression. It is constitutively expressed in lymphoid organs and highly up-regulated in the synovial tissue of patients with rheumatoid arthritis (RA), who may also generate autoantibodies to this protein. This study was undertaken to investigate the potential involvement of hnRNP A2/B1 in the pathogenesis of autoimmune arthritis, by silencing hnRNP A2/B1 expression in 2 animal models of RA. METHODS: Collagen-induced arthritis (CIA) and the K/BxN serum-transfer model were used as animal models of RA. Efficient silencing of hnRNP A2/B1 was achieved using a liposome-based carrier system for delivery of small interfering RNAs. Expression of hnRNP A2/B1 was analyzed by flow cytometry, reverse transcription-quantitative polymerase chain reaction, Western blotting, and immunohistochemistry. The number of osteoclasts was determined by tartrate-resistant acid phosphatase staining. Cytokine levels and anticollagen antibody levels were measured by enzyme-linked immunosorbent assay. RESULTS: Efficient silencing of hnRNP A2/B1 was achieved in all lymphoid organs. In both experimental models, the incidence and severity of arthritis were largely reduced and bone erosion was not detectable as compared to the control groups. Down-modulation of hnRNP A2/B1 significantly interfered with the production of proinflammatory cytokines from monocyte/macrophages, but not from T cells. Consistent with these findings, production of T cell cytokines was not impaired when cells were restimulated in vitro with type II collagen. Furthermore, levels of anticollagen antibodies were not affected by hnRNP A2/B1 silencing. CONCLUSION: Our findings suggest that hnRNP A2/B1 has an important role in regulation of the innate immune system, especially at the level of monocyte/macrophage activation. Therefore, down-modulation of hnRNP A2/B1 seems to affect primarily the effector phase of autoimmune arthritis.
27586879 Safety and efficacy of CT-P13 in Japanese patients with rheumatoid arthritis in an extensi 2017 Mar OBJECTIVES: This study aimed to evaluate the safety of CT-P13 in patients with rheumatoid arthritis (RA) during long-term treatment or after switching from innovator infliximab (IFX). METHODS: Patients who completed 54 weeks of treatment in a phase I/II study (PI/II) received CT-P13 at an initial dose of 3 mg/kg at Week 62, with dose increases permitted up to 10 mg/kg. The primary endpoint was adverse event (AE) incidence. RESULTS: Thirty-four of 38 patients in the maintenance group and 29 of 33 in the switch group reported at least one AE. Safety profiles in both groups were similar to those in PI/II. Eleven of 28 patients who were positive for anti-drug antibodies (ADA) at Week 62 discontinued the study before Week 110. Forty-one of 43 ADA-negative patients remained negative, and 10 of 28 ADA-positive patients became negative during the study. The mean DAS28 (ESR) at Week 134 was 3.166 in the maintenance group and 3.955 in the switch group. CONCLUSIONS: CT-P13 was well tolerated in patients who maintained the treatment after 54 weeks and in patients who switched to CT-P13 after 54 weeks of IFX treatment. The study also demonstrated a stable clinical efficacy of CT-P13 in RA patients.
25401232 Differences in fluorodeoxyglucose positron emission tomography/computed tomography finding 2015 Jul OBJECTIVES: To compare the fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) findings in patients with elderly-onset rheumatoid arthritis (EORA) with those in patients with polymyalgia rheumatica (PMR), two conditions with similar clinical presentations. METHODS: We retrospectively analyzed the FDG-PET/CT findings in 10 patients with EORA and 27 patients with PMR admitted to our department between 2006 and 2012. RESULTS: No significant difference was observed in the median patient ages at the time of FDG-PET/CT scans in the EORA and PMR groups (73.5 vs. 78.0 years, respectively). Significant differences in both FDG uptake scores and standardized uptake values were observed between the two groups in the ischial tuberosities, spinous processes, and wrists. No significant differences were detected in the shoulders and hips. However, specific uptake patterns were observed in each group: circular and linear uptake patterns were observed around the humeral head in the EORA group, whereas focal and non-linear uptake patterns were observed in the PMR group. Moreover, focal uptake in front of the hip joint, indicating iliopectineal bursitis, tended to be limited to the PMR group. High sensitivity (92.6%) and specificity (90%) were observed for PMR diagnoses when at least three of the following five items were satisfied: characteristic findings of shoulder and iliopectineal bursitis, FDG uptake in ischial tuberosities and spinal spinous processes, and lack of FDG uptake in the wrists. CONCLUSION: The differences in the degree of uptake at each lesion and in uptake patterns at the shoulders and hips are potentially useful for obtaining a definitive diagnosis.
25652333 Genetics of serum concentration of IL-6 and TNFα in systemic lupus erythematosus and rheu 2015 Aug Elevated concentrations of inflammatory mediators are characteristic of autoimmune disease accompanied by chronic or recurrent inflammation. We examined the hypothesis that mediators of inflammation known to be elevated in systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) are associated with genetic polymorphism previously identified in studies of inflammatory disease. Serum interleukin 6 (IL-6) and tumor necrosis factor alpha (TNFα) concentrations in patients with SLE (n = 117) or RA (n = 164) and in inflammatory disease-free control subjects (n = 172) were measured by multiplex ELISA. Candidate genes were chosen from studies of autoimmune and inflammatory disease. Genotypes were determined for 345 SNP markers in 75 genes. Association between serum analytes and single alleles was tested by linear regression. Polymorphisms in several genes were associated with IL-6 levels (including IL10, TYK2, and CD40L in SLE and DRB1, NOD2, and CSF1 in RA) or with TNFα levels (including TNFSF4 and CSF2 in SLE and PTPN2, DRB1, and NOD2 in RA). Some associations were shared between disease and control groups or between IL-6 and TNFα within a group. In conclusion, variation in genes implicated in disease pathology is associated with serum IL-6 or TNFα concentration. Some genetic associations are more apparent in healthy controls than in SLE or RA, suggesting dysregulation of the principal mediators of chronic inflammation in disease. Susceptibility genes may affect inflammatory response with variable effect on disease etiology.
27470086 Use of a risk characterisation approach to contextualise the safety profile of new rheumat 2017 Mar Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). To characterise the relative safety profile of tofacitinib to biologic disease-modifying antirheumatic drugs (bDMARDs), the accrued patient-years (pt-yrs) of exposure needed in an RA clinical trial programme to detect a potential increase in risk of specific adverse events (AEs) was determined. This case study/framework was constructed on the pt-yrs' accrual within pooled phase (P)1, P2 and P3, as well as long-term extension, studies of tofacitinib in RA (March 2015 data-cut) and published AE incidence rates for bDMARDs. Sample size calculations were based on a Poisson distribution to estimate pt-yrs' exposure required for 90 % probability that the lower bound of the 95 % confidence interval for tofacitinib/bDMARD would be >1, assuming that tofacitinib rates were 1.2×/1.5×/2.0× greater than comparator rates. AE rates for bDMARDs were derived from sources intended to optimise similarity with the tofacitinib database in terms of baseline characteristics, study duration and follow-up. Based on the tofacitinib exposure accrued (19,406 pt-yrs), data were sufficient (90 % probability) to detect potential differences over external bDMARD comparator rates in serious infections (≥1.2×), malignancies (excluding non-melanoma skin cancer [NMSC]), NMSC, major adverse cardiovascular events (MACE) and lymphoma (each ≥1.5×), as well as opportunistic infections and gastrointestinal perforations (≥2×), should they exist. This risk characterisation approach can support the comparative safety of new RA medications. To date, tofacitinib safety appears similar to approved published data from bDMARDs with respect to serious infections, malignancies (excluding NMSC), NMSC, MACE, lymphoma, opportunistic infections and gastrointestinal perforations.
26359948 Risk of Subsequent Infection Among Patients Receiving Tumor Necrosis Factor Inhibitors and 2016 Jan OBJECTIVE: To describe the incidence of subsequent serious infections in patients who received systemic drug therapy after an initial serious infection. METHODS: Patients with rheumatic conditions (rheumatoid arthritis [RA], psoriatic arthritis, ankylosing spondylitis) or psoriasis who experienced a serious infection between January 1, 2006 and December 31, 2011 were identified in a claims database. Patients were required to be continuously enrolled in the Truven Health Analytics MarketScan Research Database for 12 months prior to and at least 60 days after the date of discharge or the end of intravenous antibiotic therapy for the index serious infection. Subsequent serious infection incidence rates per 100 patient-years with 95% confidence intervals (95% CIs) were calculated for up to 18 months post-index, starting 60 days post-index. Cox proportional hazards models were used to adjust for baseline demographic and clinical characteristics, treatment duration, and changes during followup. RESULTS: Among the 21,699 patients who met the inclusion criteria, the majority (84.3%) had RA. Patients who received tumor necrosis factor (TNF) inhibitor therapy after their index infection had a lower rate of subsequent serious infections (18.1 per 100 patient-years for those treated with a TNF inhibitor alone and 17.3 per 100 patient-years for those treated with a TNF inhibitor plus a nonbiologic disease-modifying antirheumatic drug [DMARD]) compared with those treated with a nonbiologic DMARD alone (21.4 per 100 patient-years). Etanercept, either alone (adjusted hazard ratio [HR] 0.87, 95% CI 0.77-0.99) or in combination with a nonbiologic DMARD (adjusted HR 0.76, 95% CI 0.66-0.88), and infliximab (only in combination with a nonbiologic DMARD) (adjusted HR 0.80, 95% CI 0.67-0.95) were associated with a significantly lower risk of subsequent serious infections compared with a nonbiologic DMARD alone. CONCLUSION: We did not observe an increased risk of subsequent infection in patients who received TNF inhibitor treatment following a serious infection. The risk of a subsequent serious infection was lower in patients treated with both a TNF inhibitor and a nonbiologic DMARD compared with that in patients treated with a nonbiologic DMARD alone.
25832674 Reflecting on patient-centred care in pharmacy through an illness narrative. 2015 Aug Patient-centred care (PCC) is rapidly adopting a central position in discussions on the quality of healthcare, with patient-centredness deemed essential to transforming the healthcare system. PCC speaks to the quality of patient-provider relationships and has been defined as an approach to providing care that is respectful of and responsive to individual patient preferences, needs, and values, while ensuring that patient values guide all clinical decisions. However its place within pharmacy practice is unclear and is as yet undefined, particularly in relation to pharmaceutical care. Through my personal illness narrative, I briefly explore the visibility and evidence of PCC in the pharmacy literature as well as from personal experience of pharmacy care, and find it lacking. I conclude that an integrated, seamless understanding of PCC and the use of shared language within the health professions is essential in successful teamwork with both the patient and with other health professions.
26054442 [Safe use of biological therapies for the treatment of rheumatoid arthritis and spondyloar 2015 May The treatment of autoimmune rheumatic diseases has gradually improved over the last half century, which has been expanded with the contribution of biological therapies or immunobiopharmaceuticals. However, we must be alert to the possibilities of undesirable effects from the use of this class of medications. The Brazilian Society of Rheumatology (Sociedade Brasileira de Reumatologia/SBR) produced a document based on a comprehensive literature review on the safety aspects of this class of drugs, specifically with regard to the treatment of rheumatoid arthritis (RA) and spondyloarthritides. The themes selected by the participating experts, on which considerations have been established as the safe use of biological drugs, were: occurrence of infections (bacterial, viral, tuberculosis), infusion reactions, hematological, neurological, gastrointestinal and cardiovascular reactions, neoplastic events (solid tumors and hematologic neoplasms), immunogenicity, other occurrences and vaccine response. For didactic reasons, we opted by elaborating a summary of safety assessment in accordance with the previous themes, by drug class/mechanism of action (tumor necrosis factor antagonists, T-cell co-stimulation blockers, B-cell depletors and interleukin-6 receptor blockers). Separately, general considerations on safety in the use of biologicals in pregnancy and lactation were proposed. This review seeks to provide a broad and balanced update of that clinical and experimental experience pooled over the last two decades of use of immunobiological drugs for RA and spondyloarthritides treatment.
26832367 Serum levels of 14-3-3η protein supplement C-reactive protein and rheumatoid arthritis-as 2016 Feb 1 BACKGROUND: Age, C-Reactive Protein (CRP) and autoantibodies (Abs) are associated with worse prognosis in patients with recent-onset inflammatory polyarthritis (EPA). Serum 14-3-3η protein is a joint-derived biomarker that up-regulates cytokines and enzymes that perpetuate local and systemic inflammation and may contribute to joint damage. Our objective was to evaluate, over a 5-year prospective period of observation, the additional prognostic potential of serum 14-3-3η protein in EPA patients. METHODS: Clinical variables, serum and radiographs (scored according to the Sharp/van der Heijde (SvH) method) were collected serially. Relationships between serum 14-3-3η protein and other biomarkers were computed with Spearman correlations. Outcomes were Simple Disease Activity Index (SDAI) scores and joint damage progression: ΔSvH for SvH score and ΔErosion for its Erosive component. The additional predictive contribution of 14-3-3η was defined using generalized estimating equations (GEE) and generalized linear mixed models (GLMM). RESULTS: Among 331 patients, baseline 14-3-3η was ≥0.19 and ≥0.50 ng/ml in 153 (46.2 %) and 119 (36.0 %), respectively; CRP was >8.0 mg/L in 207 (62.5 %), and at least one Ab (Rheumatoid Factor, anti-CCP2 or anti-Sa/citrullinated vimentin) was positive in 170 (51.5 %). Elevated 14-3-3η levels moderately correlated with positive Abs, but not with elevated CRP. Baseline 14-3-3η ≥0.19 ng/ml was associated with more radiographic progression over 5 years. The optimal levels of baseline 14-3-3η to predict radiographic progression was defined by ROC curves at 0.50 ng/ml. Levels of 14-3-3η ≥0.50 ng/ml at baseline were associated with lower likelihoods of ever reaching SDAI remission (RR 0.79 (95 % CI 0.64-0.98), p = 0.03) and higher subsequent progression of Total and Erosion SvH scores. Elevated levels of 14-3-3η during follow-up also predicted higher subsequent progression, even in patients in SDAI remission. Decreases of 14-3-3η levels by at least 0.76 ng/ml and reversion to negative during follow-up associated with less subsequent radiographic progression. In multivariate models, elevated 14-3-3η interacted with positive Abs, elevated CRP and older age to predict subsequent radiographic progression. CONCLUSIONS: Levels of 14-3-3η protein ≥0.50 ng/ml predict poorer clinical and radiographic outcomes in EPA, both at baseline and after initiation of treatment, even in SDAI remitters. 14-3-3η, CRP, age and Abs represent independent predictors of subsequent joint damage. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT00512239 . Registered August 6, 2007.
25727209 Pathogenic functions of B cells in autoimmune diseases: IFN-γ production joins the crimin 2015 Apr B-cell depletion therapy has emerged as a powerful strategy to intercept the progression of T-cell-mediated autoimmune diseases such as rheumatoid arthritis, type 1 diabetes, or relapsing remitting multiple sclerosis. However, its mode of action remains incompletely defined, reflecting our incomplete understanding of the pathogenic functions of B cells in such pathologies. B cells can contribute to immune responses through the production of antibodies, presentation of antigen to T cells, and production of cytokines. In this issue of the European Journal of Immunology [Eur. J. Immunol. 2015. 45: 988-998], Olalekan et al. demonstrate that IFN-γ production by B cells is essential for the development of arthritis in mice. Lack of IFN-γ expression in B cells results in reduced autoimmune T-cell responses and autoantibody levels, impacting the arthritogenic reaction akin to that in B-cell depletion therapy. Together with other reports, the article by Olalekan et al. emphasizes the importance of cytokine-producing B cells in the pathogenesis of autoimmune diseases. In this commentary, I discuss how these findings shed new light on the roles of B cells as drivers of autoimmune pathogenesis, and how they more generally contribute to our understanding of the role of B cells in immunity.
27289217 Radiologic Patterning of Hallux Deformity in Rheumatoid Arthritis and Its Relationship to 2016 Sep Hallux deformities other than hallux valgus, especially those in the sagittal plane, have not yet been elucidated in the feet of patients with rheumatoid arthritis. The objectives of the present study were to classify rheumatoid arthritis hallux deformity in both the horizontal and the sagittal planes and investigate its relationship with flatfoot. Using a cross-sectional study design, we assessed patients with rheumatoid arthritis (527 feet in 274 patients) using radiographs and classified the deformity patterns of the great toes using cluster analysis. Of the 274 patients, the range of motion in the metatarsophalangeal joint was clinically investigated in 44 (16.1%) patients. The great toes could be divided into 5 clusters according to the characteristic configuration as follows: cluster I (normal type), cluster II (hallux valgus type), cluster III (boutonniere type), cluster IV (boutonniere with hallux valgus type), and cluster V (swan-neck type). Radiographic measurements revealed the characteristic deformities of each cluster, including splayed foot for cluster II; flat foot, metatarsal primus elevatus, and plantar displacement of the proximal phalanx for cluster III; and a mixture of these characteristics for cluster IV. Plantar displacement of the proximal phalanx, which was a specific characteristic of the boutonniere deformity, correlated significantly with the decreased dorsiflexion in the metatarsophalangeal joint. Our classification method revealed the relationship of hallux deformity in the sagittal plane to flatfoot and also demonstrated the usefulness of measuring basal phalanx displacement in predicting the range of motion of the metatarsophalangeal joint.
26937917 Body Mass Index and Risk of Rheumatoid Arthritis: A Meta-Analysis of Observational Studies 2016 Feb Although many epidemiological studies have investigated the association between body mass index (BMI) and risk of rheumatoid (RA), the results have been inconsistent. Therefore, we performed a dose-response meta-analysis to quantify the dose-response association between BMI and RA risk.We systematically searched PubMed, Embase, and Web of Science databases and reference lists of articles for relevant studies published before August 2014 using terms related to BMI and RA. Fixed or random-effects models were used to estimate the pooled relative risk (RR) with 95% confidence interval (CI). Several subgroup analyses, sensitivity analyses, and publication bias tests were performed to explore potential study heterogeneity and biasThirteen studies involving 400,609 participants and 13,562 RA cases were included. The RR of RA was 1.21 (95% CI: 1.02-1.44) for obesity, 1.05 (95% CI: 0.97-1.13) for overweight. The risk of RA increased by 13% (RR: 1.13; 95% CI: 1.01-1.26) for every 5 kg/m increase in BMI. The subgroup analyses showed a positive association between BMI and RA risk only in women with an RR of 1.26 (95% CI: 1.12-1.40) for obesity and 1.12(95% CI: 1.07-1.18) for every 5 kg/m increase in BMI. Also, an increased risk of RA was found in sero-negative subgroup with an RR of 1.47 (95% CI: 1.11-1.96) for obesity and 1.21 (95% CI: 1.06-1.39) for every 5 kg/m increase in BMI.There is evidence that obesity is a risk factor for developing of RA. Furthermore, the positive association between BMI and RA risk may be stronger among women than men.
26095630 Monocytes from patients with rheumatoid arthritis and type 2 diabetes mellitus display an 2015 Oct A better understanding about the mechanisms involved in the pathogenesis of type 2 diabetes mellitus (T2D) showed that inflammatory cytokines such as tumour necrosis factor (TNF) and interleukin (IL)-1β play a pivotal role, mirroring data largely reported in rheumatoid arthritis (RA). IL-1β is produced mainly by monocytes (MO), and hyperglycaemia may be able to modulate, in the cytoplasm of these cells, the assembly of a nucleotide-binding domain and leucine-rich repeat containing family pyrin (NLRP3)-inflammosome, a cytosolic multi-protein platform where the inactive pro-IL-1β is cleaved into active form, via caspase-1 activity. In this paper, we evaluated the production of IL-1 β and TNF, in peripheral blood MO of patients affected by RA or T2D or both diseases, in order to understand if an alteration of the glucose metabolism may influence their proinflammatory status. Our data showed, after 24 h of incubation with different glucose concentrations, a significantly increased production of IL-1β and TNF in all evaluated groups when compared with healthy controls. However, a significant increase of IL-1β secretion by T2D/RA was observed when compared with other groups. The analysis of relative mRNA expression confirmed these data. After 24 h of incubation with different concentrations of glucose, our results showed a significant increase in NLRP3 expression. In this work, an increased production of IL-1β by MO obtained from patients affected by both RA and T2D via NLRP3-inflammasome activation may suggest a potential IL-1β targeted therapy in these patients.
24532676 High-density genotyping of immune loci in Koreans and Europeans identifies eight new rheum 2015 Mar OBJECTIVE: A highly polygenic aetiology and high degree of allele-sharing between ancestries have been well elucidated in genetic studies of rheumatoid arthritis. Recently, the high-density genotyping array Immunochip for immune disease loci identified 14 new rheumatoid arthritis risk loci among individuals of European ancestry. Here, we aimed to identify new rheumatoid arthritis risk loci using Korean-specific Immunochip data. METHODS: We analysed Korean rheumatoid arthritis case-control samples using the Immunochip and genome-wide association studies (GWAS) array to search for new risk alleles of rheumatoid arthritis with anticitrullinated peptide antibodies. To increase power, we performed a meta-analysis of Korean data with previously published European Immunochip and GWAS data for a total sample size of 9299 Korean and 45,790 European case-control samples. RESULTS: We identified eight new rheumatoid arthritis susceptibility loci (TNFSF4, LBH, EOMES, ETS1-FLI1, COG6, RAD51B, UBASH3A and SYNGR1) that passed a genome-wide significance threshold (p<5×10(-8)), with evidence for three independent risk alleles at 1q25/TNFSF4. The risk alleles from the seven new loci except for the TNFSF4 locus (monomorphic in Koreans), together with risk alleles from previously established RA risk loci, exhibited a high correlation of effect sizes between ancestries. Further, we refined the number of single nucleotide polymorphisms (SNPs) that represent potentially causal variants through a trans-ethnic comparison of densely genotyped SNPs. CONCLUSIONS: This study demonstrates the advantage of dense-mapping and trans-ancestral analysis for identification of potentially causal SNPs. In addition, our findings support the importance of T cells in the pathogenesis and the fact of frequent overlap of risk loci among diverse autoimmune diseases.