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ID PMID Title PublicationDate abstract
29148406 High 3-year golimumab survival in patients with rheumatoid arthritis, ankylosing spondylit 2018 Mar OBJECTIVES: Our primary objective was to study the long-term survival on drug (SOD) of patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ankylosing spondylitis (AS) treated with golimumab (GLM) in real life settings. METHODS: This was a retrospective, observational study of all patients treated with GLM in 4 Academic Centres in Greece during a 4-year period (09/2010-06/2014). SOD was analysed using Kaplan-Meier survival analysis, while Cox regression analysis estimating hazard ratios (HRs) for different baseline variables associated with drug discontinuation was performed for each disease. RESULTS: 328 patients (RA: 166, PsA: 82, AS: 80) were included. The estimated SOD at 2 and 3 years was 68% and 62% overall and was better for AS (79% and 76%) compared to RA (69% and 60%, p=0.067) and PsA (58% and 53%, p=0.001) patients; no difference was noted between RA and PsA patients (p=0.204). There was no difference in SOD between biologic-naïve and experienced nor between non-biologic co-treated or GLM monotherapy treated patients. Seropositivity (rheumatoid factor and/or anti-cyclic citrullinated peptide antibodies) was associated with a lower risk for GLM discontinuation by multivariate analysis (HR=0.5, 95% CI=0.0.25-1.1, p=0.05) in RA patients. During 606 patient-years of follow-up, 11 (3.3%) patients discontinued GLM due to adverse events (AE), accounting for 11% of treatment discontinuations. The rates of serious AEs and serious infections were 2.3 and 1.0/100-patient-years, respectively. CONCLUSIONS: In this real-life study, GLM showed a high 3-year SOD in patients with inflammatory arthritides with a low rate of discontinuation due to AEs.
28507184 Importance of Obtaining Remission for Work Productivity and Activity of Patients with Rheu 2017 Aug OBJECTIVE: To identify the factors relevant to work and activity impairment in patients with rheumatoid arthritis. METHODS: In total, 1274 consecutive patients were included. Work and activity impairment were measured by the Work Productivity and Activity Impairment questionnaire, and related clinical factors were examined. RESULTS: Work and activity impairment was reported by 67.4% of the patients. Multivariable linear regression analyses revealed pain and non-remission to be associated with activity impairment and presenteeism. Patients in remission had significantly less activity impairment and presenteeism than those with low disease activity. CONCLUSION: Remission achievement is essential for ensuring work performance and activity.
28569267 Biologics registers in RA: methodological aspects, current role and future applications. 2017 Aug The beginning of the 21st century saw a biopharmaceutical revolution in the treatment of inflammatory rheumatic diseases, particularly rheumatoid arthritis. The fast-evolving use of biologic therapies highlighted the need to develop registers at national and international levels with the aim of collecting long-term data on patient outcomes. Over the past 15 years, many biologics registers have contributed a wealth of data and provided robust and reliable evidence on the use, effectiveness and safety of these therapies. The unavoidable challenges posed by the continuous introduction of new therapies, particularly with regard to understanding their long-term safety, highlights the importance of learning from experience with established biologic therapies. In this Perspectives article, the role of biologics registers in bridging the evidence gap between efficacy in clinical trials and real-world effectiveness is discussed, with a focus on methodological aspects of registers, their unique features and challenges and their role going forward.
28855496 A Retrospective Study: The Significance of Combined Testing of Serum Markers for Diagnosis 2017 Aug 31 BACKGROUND There have been few studies on the value of various antibody combinations in rheumatoid arthritis (RA) diagnosis, and a lack of studies with large sample sizes, especially in the Chinese population. This study retrospectively evaluated the diagnostic value of a combined assay of five auto-antibodies [anti-cyclic citrullinated peptide (anti-CCP), anti-keratin (AKA), anti-RA 33, glucose-6-phosphate isomerase (GPI), and rheumatoid factor (RF)] for RA. MATERIAL AND METHODS Data were obtained from 5,725 patients with rheumatic diseases in Southwest Hospital of Chongqing from 2011 to 2014. Detection of the five serological markers was performed for all study patients using the appropriate method for each antibody. RESULTS It was found that of the 5,725 patients, the positive rates for RF, anti-CCP, anti-RA 33, AKA, and GPI were 52.5%, 40.1%, 12.8%, 12.0%, and 50.0% respectively. In RA patients, the positive rates were 83.3%, 68.5%, 16.6%, 20.8%, and 77.9% respectively, which were all significantly higher than those detected in patients with the other diseases (p<0.01). The areas under the receiver operator characteristic (ROC) curve for RF, anti-CCP, anti-RA 33, AKA, and GPI were 0.857, 0.831, 0.528, 0.602, and 0.822 respectively, indicating that these five serological markers display favorable diagnostic value for RA. There were positive correlations between anti-CCP antibody and RF and GPI (p<0.01) and between RF and GPI (p<0.01), but no correlation between anti-RA 33 and AKA (p<0.01). The specificity of the combination of anti-CCP, AKA, and GPI was 100% for RA diagnosis. CONCLUSIONS The combined assay of serological markers significantly improved the diagnostic specificity for RA. The diagnostic value of RF for RA was the highest and the combined assay for anti-CCP, AKA, and GPI had the highest specificity for RA diagnosis.
27561790 Increased sympathetic nerve activity and reduced cardiac baroreflex sensitivity in rheumat 2017 Feb 1 KEY POINTS: Rheumatoid arthritis (RA) is a chronic inflammatory condition associated with an increased risk of cardiovascular mortality. Increased sympathetic nerve activity and reduced cardiac baroreflex sensitivity heighten cardiovascular risk, althogh whether such autonomic dysfunction is present in RA is not known. In the present study, we observed an increased sympathetic nerve activity and reduced cardiac baroreflex sensitivity in patients with RA compared to matched controls. Pain was positively correlated with sympathetic nerve activity and negatively correlated with cardiac baroreflex sensitivity. The pattern of autonomic dysfunction that we describe may help to explain the increased cardiovascular risk in RA, and raises the possibility that optimizing pain management may resolve autonomic dysfunction in RA. ABSTRACT: Rheumatoid arthritis (RA) is a chronic inflammatory condition associated with increased cardiovascular morbidity/mortality and an incompletely understood pathophysiology. In animal studies, central and blood borne inflammatory cytokines that can be elevated in RA evoke pathogenic increases in sympathetic activity and reductions in baroreflex sensitivity (BRS). We hypothesized that muscle sympathetic nerve activity (MSNA) was increased and BRS decreased in RA. MSNA, blood pressure and heart rate (HR) were recorded in age- and sex-matched RA-normotensive (n = 13), RA-hypertensive patients (RA-HTN; n = 17), normotensive (NC; n = 17) and hypertensive controls (HTN; n = 16). BRS was determined using the modified Oxford technique. Inflammation and pain were determined using serum high sensitivity C-reactive protein (hs-CRP) and a visual analogue scale (VAS), respectively. MSNA was elevated similarly in RA, RA-HTN and HTN patients (32 ± 9, 35 ± 14, 37 ± 8 bursts min(-1) ) compared to NC (22 ± 9 bursts min(-1) ; P = 0.004). Sympathetic BRS was similar between groups (P = 0.927), whereas cardiac BRS (cBRS) was reduced in RA, RA-HTN and HTN patients [5(3-8), 4 (2-7), 6 (4-9) ms mmHg(-1) ] compared to NC [11 (8-15) ms mmHg(-1) ; P = 0.002]. HR was independently associated with hs-CRP. Increased MSNA and reduced cBRS were associated with hs-CRP although confounded in multivariable analysis. VAS was independently associated with MSNA burst frequency, cBRS and HR. We provide the first evidence for heightened sympathetic outflow and reduced cBRS in RA that can be independent of hypertension. In RA patients, reported pain was positively correlated with MSNA and negatively correlated with cBRS. Future studies should assess whether therapies to ameliorate pain and inflammation in RA restores autonomic balance and reduces cardiovascular events.
28957553 Disease activity dynamics in rheumatoid arthritis: patients' self-assessment of disease ac 2017 Oct 1 OBJECTIVES: The aim was to evaluate patient self-assessment of RA disease activity in terms of Routine Assessment of Patient Index Data (RAPID) scores via a Web-based smartphone application (WebApp). METHODS: In this prospective, multicentre study, adult RA patients were examined by a rheumatologist at baseline and after 3 months. Patients were asked to complete WebApp questionnaires weekly. The time course of patient-assessed RAPID3/4 scores and their correlations with rheumatologist-assessed DAS28, as well as Clinical and Simplified Disease Activity Indices (CDAI/SDAI), were evaluated. RESULTS: Eighty patients were included in the analysis (median RA duration, 4.5 years; age, 57 years; 59% female). At baseline, there was a moderate to strong correlation between RAPID3 and DAS28 (r = 0.63), CDAI (r = 0.65) and SDAI (r = 0.61) scores. Similar or stronger correlations were seen at the 3-month follow-up visit (DAS28 r = 0.66, CDAI r = 0.71 and SDAI r = 0.61). Similar correlations were seen between RAPID4 and rheumatologist assessments. Correlations were not influenced by demographics or RA treatment. In the 3-month period, the RAPID3 score changed into a higher severity category than the category at baseline at least once in 47% of patients. When DAS28 scores were predicted from the RAPID3, 11% of patients had an increase of > 1 DAS28 unit during the 3-month observation period. CONCLUSION: Web-based patient assessments were strongly correlated with rheumatologist assessments of RA activity and showed considerable variation during follow-up. This provides a rationale for further exploration of their use as cost-effective tools to monitor RA activity between outpatient visits and to optimize tight control strategies.
27697765 EULAR recommendations for cardiovascular disease risk management in patients with rheumato 2017 Jan Patients with rheumatoid arthritis (RA) and other inflammatory joint disorders (IJD) have increased cardiovascular disease (CVD) risk compared with the general population. In 2009, the European League Against Rheumatism (EULAR) taskforce recommended screening, identification of CVD risk factors and CVD risk management largely based on expert opinion. In view of substantial new evidence, an update was conducted with the aim of producing CVD risk management recommendations for patients with IJD that now incorporates an increasing evidence base. A multidisciplinary steering committee (representing 13 European countries) comprised 26 members including patient representatives, rheumatologists, cardiologists, internists, epidemiologists, a health professional and fellows. Systematic literature searches were performed and evidence was categorised according to standard guidelines. The evidence was discussed and summarised by the experts in the course of a consensus finding and voting process. Three overarching principles were defined. First, there is a higher risk for CVD in patients with RA, and this may also apply to ankylosing spondylitis and psoriatic arthritis. Second, the rheumatologist is responsible for CVD risk management in patients with IJD. Third, the use of non-steroidal anti-inflammatory drugs and corticosteroids should be in accordance with treatment-specific recommendations from EULAR and Assessment of Spondyloarthritis International Society. Ten recommendations were defined, of which one is new and six were changed compared with the 2009 recommendations. Each designated an appropriate evidence support level. The present update extends on the evidence that CVD risk in the whole spectrum of IJD is increased. This underscores the need for CVD risk management in these patients. These recommendations are defined to provide assistance in CVD risk management in IJD, based on expert opinion and scientific evidence.
29213125 The role of semaphorins in immune responses and autoimmune rheumatic diseases. 2018 Jan Semaphorins have a well-characterized role in guiding axon repulsion during development; however, the important contribution of these proteins in immunity is becoming increasingly clear. Immunoregulatory semaphorins, termed 'immune semaphorins', have roles in regulating immune cell activation, differentiation, mobility and migration. These proteins are also intimately associated with the pathogenesis of autoimmune diseases including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), systemic sclerosis (SSc) and anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). This Review discusses the pathogenic functions of immune semaphorins, as well as the potential use of these molecules as diagnostic markers and therapeutic targets for the treatment of autoimmune diseases.
28250137 Mortality from Musculoskeletal Disorders Including Rheumatoid Arthritis in Southern Sweden 2017 May OBJECTIVE: To assess mortality related to musculoskeletal (MSK) disorders and rheumatoid arthritis (RA), specifically, among adults (aged ≥ 20 yrs) in southern Sweden using the multiple-cause-of-death approach. METHODS: All death certificates (DC; n = 201,488) from 1998 to 2014 for adults in the region of Skåne were analyzed when mortality from MSK disorders and RA was listed as the underlying and nonunderlying cause of death (UCD/NUCD). Trends in age-standardized mortality rates (ASMR) were evaluated using joinpoint regression, and associated causes were identified by age- and sex-adjusted observed/expected ratios. RESULTS: MSK (RA) was mentioned on 2.8% (0.8%) of all DC and selected as UCD in 0.6% (0.2%), with higher values among women. Proportion of MSK disorder deaths from all deaths increased from 2.7% in 1998 to 3.1% in 2014, and declined from 0.9% to 0.5% for RA. The mean age at death was higher in DC with mention of MSK/RA than in DC without. The mean ASMR for MSK (RA) was 15.5 (4.3) per 100,000 person-years and declined by 1.1% (3.8%) per year during 1998-2014. When MSK/RA were UCD, pneumonia and heart failure were the main NUCD. When MSK/RA were NUCD, the leading UCD were ischemic heart disease and neoplasms. The greatest observed/expected ratios were seen for infectious diseases (including sepsis) and blood diseases. CONCLUSION: We observed significant reduction in MSK and RA mortality rates and increase in the mean age at death. Further analyses are required to investigate determinants of these improvements in MSK/RA survival and their potential effect on the Swedish healthcare systems.
27324882 Effect of spa therapy with saline balneotherapy on oxidant/antioxidant status in patients 2017 Jan Oxidative stress has been shown to play a contributory role in the pathogenesis of rheumatoid arthritis (RA). Recent studies have provided evidence for antioxidant properties of spa therapy. The purpose of this study is to investigate whether spa therapy with saline balneotherapy has any influence on the oxidant/antioxidant status in patients with RA and to assess clinical effects of spa therapy. In this investigator-blind randomized controlled trial, we randomly assigned 50 patients in a 1:1 ratio to spa therapy plus standard drug treatment (spa group) or standard drug treatment alone (control group). Spa group followed a 2-week course of spa therapy regimen consisting of a total of 12 balneotherapy sessions in a thermal mineral water pool at 36-37 °C for 20 min every day except Sunday. All clinical and biochemical parameters were assessed at baseline and after spa therapy (2 weeks). The clinical parameters were pain intensity, patient global assessment, physician global assessment, Health Assessment Questionnaire disability index (HAQ-DI), Disease Activity Score for 28-joints based on erythrocyte sedimentation rate (DAS28-4[ESR]). Oxidative status parameters were malondialdehyde (MDA), nonenzymatic superoxide radical scavenger activity (NSSA), antioxidant potential (AOP), and superoxide dismutase (SOD). The NSSA levels were increased significantly in the spa group (p = 0.003) but not in the control group (p = 0.509); and there was a trend in favor of spa therapy for improvements in NSSA levels compared to control (p = 0.091). Significant clinical improvement was found in the spa group compared to the control in terms of patient global assessment (p = 0.011), physician global assessment (p = 0.043), function (HAQ-DI) (p = 0.037), disease activity (DAS28-4[ESR]) (0.044) and swollen joint count (0.009), and a trend toward improvement in pain scores (0.057). Spa therapy with saline balneotherapy exerts antioxidant effect in patients with RA as reflected by the increase in NSSA levels after spa therapy; whether this antioxidant effect contributes to the clinical improvements observed remains to be verified.
28916714 Interleukin-6 blockade raises LDL via reduced catabolism rather than via increased synthes 2017 Nov OBJECTIVES: Patients with rheumatoid arthritis (RA) have reduced serum low-density lipoprotein cholesterol (LDL-c), which increases following therapeutic IL-6 blockade. We aimed to define the metabolic pathways underlying these lipid changes. METHODS: In the KALIBRA study, lipoprotein kinetic studies were performed on 11 patients with severe active RA at baseline and following three intravenous infusions of the IL-6R blocker tocilizumab. The primary outcome measure was the fractional catabolic rate (FCR) of LDL. RESULTS: Serum total cholesterol (4.8 vs 5.7 mmol/L, p=0.003), LDL-c (2.9 vs 3.4 mmol/L, p=0.014) and high-density lipoprotein cholesterol (1.23 vs 1.52 mmol/L, p=0.006) increased following tocilizumab therapy. The LDL FCR fell from a state of hypercatabolism to a value approximating that of the normal population (0.53 vs 0.27 pools/day, p=0.006). Changes in FCR correlated tightly with changes in serum LDL-c and C-reactive protein but not Clinical Disease Activity Index. CONCLUSIONS: Patients with RA have low serum LDL-c due to hypercatabolism of LDL particles. IL-6 blockade normalises this catabolism in a manner associating with the acute phase response (and thus hepatic IL-6 signalling) but not with RA disease activity as measured clinically. We demonstrate that IL-6 is one of the key drivers of inflammation-driven dyslipidaemia.
29102955 Development and psychometric validation of a patient-reported outcome measure to assess fe 2018 Feb OBJECTIVES: To develop and validate an outcome measure for assessing fears in patients with rheumatoid arthritis (RA) and axial spondyloarthritis (axSpA). METHODS: Fears were identified in a qualitative study, and reformulated as assertions with which participants could rate their agreement (on a 0-10 numeric rating scale). A cross-sectional validation study was performed including patients diagnosed with RA or axSpA. Redundant items (correlation >0.65) were excluded. Internal consistency (Cronbach's α) and factorial structure (principal component analysis) were assessed. Patients were classified into fear levels (cluster analysis). Associations between patient variables and fear levels were evaluated using multiple logistic regression. RESULTS: 672 patients were included in the validation study (432 RA, 240 axSpA); most had moderate disease activity and were prescribed biologics. The final questionnaire included 10 questions with high internal consistency (α: 0.89) and a single dimension. Mean scores (±SD) were 51.2 (±25.4) in RA and 60.5 (±22.9) in axSpA. Groups of patients with high (17.2%), moderate (41.1%) and low (41.7%) fear scores were identified. High fear scores were associated with high Arthritis Helplessness Index scores (OR 6.85, 95% CI (3.95 to 11.87)); high Hospital Anxiety and Depression Scale anxiety (OR 5.80, 95% CI (1.19 to 4.22)) and depression (OR 2.37, 95% CI (1.29 to 4.37)) scores; low education level (OR 3.48, 95% CI (1.37 to 8.83)); and high perceived disease activity (OR 2.36, 95% CI (1.10 to 5.04)). CONCLUSIONS: Overall, 17.2% of patients had high fear scores, although disease was often well controlled. High fear scores were associated with psychological distress. This questionnaire could be useful both in routine practice and clinical trials.
28109308 Semaphorin 7A as a potential immune regulator and promising therapeutic target in rheumato 2017 Jan 21 BACKGROUND: Semaphorin 7A (Sema7A) is expressed by several different classes of lymphoid and myeloid cells and is a potent immunomodulator. We examined the role of Sema7A in modulating cellular immune responses and to provide experimental data validating the therapeutic potential of Sema7A in rheumatoid arthritis (RA). METHODS: Soluble Sema7A (sSema7A) levels in the serum and synovial fluid from patients with RA or osteoarthritis, as well as cytokine secretions, were analyzed with an enzyme-linked immunosorbent assay. The cell surface levels and transcripts of Sema7A were evaluated in T cells and monocytes from patients with RA. The effect of Sema7A on the functions of primary T cells isolated from the peripheral blood of healthy donors was observed. Detection of the activation of the signal mediator focal adhesion kinase was performed by Western blotting. Shedding of sSema7A was evaluated in monocytes. The introduction of anti-Sema7A antibody to mice with collagen-induced arthritis (CIA) was observed in vivo. RESULTS: Upregulation of sSema7A levels in both the serum and synovial fluid of patients with RA was correlated with disease activity markers. sSema7A markedly increased Th1/Th17 cytokine secretion and induced evident upregulation of T-bet and retinoic acid receptor-related orphan nuclear receptor γt levels in T cells. Cell surface Sema7A was cleaved by a disintegrin and metalloprotease 17 (ADAM17) in monocytes. Interleukin-6 and tumor necrosis factor-α stimulated ADAM17 secretion in synovial macrophages. Blocking of β1-integrin abrogated the Sema7A-mediated cytokine secretion. Treatment with an anti-Sema7A antibody significantly attenuated CIA. CONCLUSIONS: These findings indicate that Sema7A as a potent activator of T cells and monocytes in the immune response contributes to the inflammation and progression of RA, suggesting its therapeutic potential in the treatment of RA.
29041951 A new bioassay for measuring the strength of IL-6/STAT3 signal inhibition by tocilizumab i 2017 Oct 17 BACKGROUND: Interleukin-6 (IL-6) transduces signals via phosphorylation of STAT3 (pSTAT3). Tocilizumab (TCZ) is an IL-6 receptor blocker, which, when administered intravenously every 4 weeks, efficiently ameliorates rheumatoid arthritis (RA). Since IL-6 signal strength varies among patients with RA, the intensity necessary for appropriate IL-6 signal inhibition by TCZ might vary between individuals. In a previous study, we have examined the clinical utility of increasing (dosing interval shortened to 3 weeks) and decreasing (interval extended to 5 weeks) the dose frequency of TCZ. However, there is currently no established method for accurately measuring the strength of IL-6 signal inhibition by TCZ among individual patients. We therefore sought to develop such an assay. METHODS: Whole blood samples were collected from RA patients with low disease activity (clinical disease activity index (CDAI) ≤ 10) who were treated with TCZ at dosing intervals of 3 weeks (3-week group, n = 10), 4 weeks (4-week group, n = 10) or 5 weeks (5-week group, n = 10), or with methotrexate (control group, n = 10). Recombinant human IL-6 (0, 0.1, 1, 10, 100 ng/ml) was exogenously added to whole blood and the proportion of pSTAT3-positive CD4+ T cells (%pSTAT3+/CD4+) was measured by Phosflow cytometric analysis. RESULTS: The addition of exogenous IL-6 increased the proportion of pSTAT3-positive CD4+ T cells in a dose-dependent manner in each group. Inhibition of IL-6 signaling was strongest in the 3-week dosing group, followed by the 4-week, 5-week and control group. Significant differences in %pSTAT3+/CD4+ cells were observed between dose interval groups when stimulated with 10 ng/ml and 100 ng/ml of IL-6. CONCLUSION: Assessment of the proportion of pSTAT3-positive CD4+ T cells under IL-6 stimulation is a highly sensitive and useful method for determining differences in the strength of IL-6 signal inhibition in patients treated with TCZ. It is suggested that different TCZ treatment intervals were necessary to lower disease activity in each group of patients, and these findings also indicate that the IL-6 signaling pathway may differ in each RA patient. Our assay may support strategies for optimizing TCZ treatment in RA patients.
28483543 Vaccinations and risk of systemic lupus erythematosus and rheumatoid arthritis: A systemat 2017 Jul BACKGROUND: In the past several years, more and more studies proposed some concerns on the possibly increased risk of autoimmune diseases in individuals receiving vaccinations, but published studies on the associations of vaccinations with risks of systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) reported conflicting findings. A systematic review and meta-analysis was carried out to comprehensively evaluate the relationship between vaccinations and risk of SLE and RA. METHODS: Pubmed, Web of Science and Embase were searched for observational studies assessing the associations of vaccinations with risks of RA and SLE. Two authors independently extracted data from those eligible studies. The quality of eligible studies was assessed by using the Newcastle-Ottawa Scale (NOS). The pooled relative risk (RR) with 95% confidence intervals (CIs) was used to measure the risk of RA and SLE associated with vaccinations, and was calculated through random-effect meta-analysis. RESULTS: Sixteen observational studies were finally considered eligible, including 12 studies on the association between vaccinations and SLE risk and 13 studies on the association between vaccinations and RA risk. The pooled findings suggested that vaccinations significantly increased risk of SLE (RR=1.50; 95%CI 1.05-2.12, P=0.02). In addition, there was an obvious association between vaccinations and increased risk of RA (RR=1.32; 95%CI 1.09-1.60, P=0.004). Meta-analysis of studies reporting outcomes of short vaccinated time also suggested that vaccinations could significantly increase risk of SLE (RR=1.93; 95%CI 1.07-3.48, P=0.028) and RA (RR=1.48; 95%CI 1.08-2.03, P=0.015). Sensitivity analyses in studies with low risk of bias also found obvious associations of vaccinations with increased risk of RA and SLE. CONCLUSION: This study suggests that vaccinations are related to increased risks of SLE and RA. More and larger observational studies are needed to further verify the findings above and to assess the associations of vaccinations with other rheumatic diseases.
28370244 Autoantibodies against citrullinated histone H3 in rheumatoid arthritis and periodontitis 2017 Jun AIM: To determine the presence of citrullinated histones in inflamed periodontal tissue and to determine the presence of anti-citrullinated histone autoantibodies in sera from patients with rheumatoid arthritis (RA) and periodontitis (PD) patients. METHODS: The presence of citrullinated histone H3, PAD4 and CD68 was determined in 15 periodontal tissue biopsies from PD patients by immunohistochemistry. Sera from 36 healthy controls (HC), 113 PD patients and 84 patients with RA were assessed on presence of autoantibodies against citrullinated histones by Western blot and against citrullinated histone H3 by ELISA. RESULTS: Citrullinated histone H3, PAD4 and CD68 were present in periodontal tissue from nine (60%), 14 (93%) and 13 (87%) PD patients, respectively. Anti-citrullinated histone H3 autoantibodies were found in 33 (39%) patients with RA compared to three (8%) HC and 11 (10%) PD patients. Anti-citrullinated histone H3 levels were higher in anti-cyclic citrullinated peptide (anti-CCP)-positive compared to anti-CCP-negative patients with RA (p = .0008) and correlated moderately with anti-CCP levels (ρ = .22). No associations were found between anti-citrullinated histone H3 levels and periodontal status or smoking behaviour of patients with RA. CONCLUSION: PD patients are exposed to citrullinated histone H3 in inflamed periodontal tissue. Citrullinated histone H3 is targeted by autoantibodies present in RA sera. This supports a role for periodontitis in generation of antigens targeted by autoantibodies directed against citrullinated proteins.
28363728 Pelvic radiotherapy in the setting of rheumatoid arthritis: Refining the paradigm. 2017 Apr PURPOSE: Conflicting results concerning the toxicity of radiotherapy in the setting of rheumatoid arthritis were reported in literature. This work describes the toxicity profiles of patients with rheumatoid arthritis undergoing pelvic radiotherapy for gynecologic malignancies at our institution. PATIENTS AND METHODS: Charts of patients with rheumatoid arthritis who underwent pelvic radiotherapy for cervical or endometrial cancer in a curative intent at the Gustave-Roussy Cancer Campus between 1990 and 2015 were reviewed for treatment-related toxicities. Acute and late effects were graded as per the Common Terminology Criteria for Adverse Events version 4.0 scoring system. RESULTS: Eight patients with cervical cancer and three with endometrial cancer were identified. Median follow-up was 56 months. Median external beam radiotherapy dose was 45Gy. All patients received a brachytherapy boost using either pulse- or low-dose rate technique. Concomitant chemotherapy was used in seven cases. Median time from rheumatoid arthritis diagnosis to external beam radiation therapy was 5 years. No severe acute gastrointestinal or genitourinary toxicity was reported. One patient had grade 3 dermatitis. Any late toxicity occurred in 7 /11 patients, and one patient experienced severe late toxicities. One patient with overt systemic rheumatoid arthritis symptoms at the time of external beam radiation therapy experienced late grade 3 ureteral stenosis, enterocolitis and lumbar myelitis. CONCLUSION: Pelvic radiotherapy, in the setting of rheumatoid arthritis, appears to be feasible, with potentially slight increase in low grade late events compared to other anatomic sites. Patients with overt systemic rheumatoid arthritis manifestation at the time of radiotherapy might be at risk of potential severe toxicities.
28199905 Spontaneous ultra-weak photon emission in correlation to inflammatory metabolism and oxida 2017 Mar The increasing prevalence of rheumatoid arthritis has driven the development of new approaches and technologies for investigating the pathophysiology of this devastating, chronic disease. From the perspective of systems biology, combining comprehensive personal data such as metabolomics profiling with ultra-weak photon emission (UPE) data may provide key information regarding the complex pathophysiology underlying rheumatoid arthritis. In this article, we integrated UPE with metabolomics-based technologies in order to investigate collagen-induced arthritis, a mouse model of rheumatoid arthritis, at the systems level, and we investigated the biological underpinnings of the complex dataset. Using correlation networks, we found that elevated inflammatory and ROS-mediated plasma metabolites are strongly correlated with a systematic reduction in amine metabolites, which is linked to muscle wasting in rheumatoid arthritis. We also found that increased UPE intensity is strongly linked to metabolic processes (with correlation co-efficiency |r| value >0.7), which may be associated with lipid oxidation that related to inflammatory and/or ROS-mediated processes. Together, these results indicate that UPE is correlated with metabolomics and may serve as a valuable tool for diagnosing chronic disease by integrating inflammatory signals at the systems level. Our correlation network analysis provides important and valuable information regarding the disease process from a system-wide perspective.
28954112 Norwegian scabies in a patient treated with Tripterygium glycoside for rheumatoid arthriti 2017 Jul We report an 80-year-old male patient with severe rheumatoid arthritis who was treated with tripterygium glycoside, an immunosuppressive agent made from the extract of a Chinese medicinal herb called Tripterygium wilfordii Hook F. The patient had no apparent skin lesions before the treatment, but he developed aggressive hyperkeratotic lesions with rapid progression after using tripterygium glycoside. He was repeatedly diagnosed with eczema, but treatment failed to achieve efficacy. Interestingly, a microscopic examination of the lesions revealed numerous scabies mites and eggs. Thus, we confirmed the diagnosis of Norwegian scabies infection. Treated with crotamiton 10% cream and 10% sulfur ointment for one month, the patient's clinical symptoms disappeared.
29271968 [Humanization of Murine Monoclonal anti-hTNF Antibody: The F10 Story]. 2017 Nov Tumor necrosis factor (TNF) is a proinflammatory cytokine implicated in pathogenesis of multiple autoimmune and inflammatory diseases. Anti-TNF therapy has revolutionized the therapeutic paradigms of autoimmune diseases and became one of the most successful examples of the clinical use of monoclonal antibodies. Currently, anti-TNF therapy is used by millions of patients worldwide. At the moment, fully human anti-TNF antibody Adalimumab is the best-selling anti-cytokine drug in the world. Here, we present a story about a highly potent anti-TNF monoclonal antibody initially characterized more than 20 years ago and further developed into chimeric and humanized versions. We present comparative analysis of this antibody with Infliximab and Adalimumab.