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Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
23558378 Biological therapies for rheumatoid arthritis: progress to date. 2013 Aug Biologic drugs for the management of rheumatoid arthritis (RA) have revolutionized the therapeutic armamentarium with the development of several novel monoclonal antibodies, which include murine, chimeric, humanized, fully human antibodies and fusion proteins. These biologics bind to their targets with high affinity and specificity. Since 1998, nine different biologics have been approved by the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) for the treatment of RA, and several others are in different stages of clinical trials. This field is in continuous evolution and new biologics are tested every year. Therefore a precise analysis is required in order to have a detailed and updated state of the art of this field. In this review, our main aim is to analyse all available biological therapies that are FDA and EMA approved for the treatment of RA and also those that are in clinical trials for the management of RA patients.
25044486 Self-perceived oral health and periodontal parameters in chronic periodontitis patients wi 2016 Feb AIM: It is hypothesized that self-perceived oral health and periodontal status are worse in chronic periodontitis (CP) patients with rheumatoid arthritis (RA) compared to CP patients without RA. The aim of the present study was to assess self-perceived oral health and periodontal parameters in CP patients with and without RA. METHODS: Fifty CP patients with RA and 50 CP patients without RA were included. Information regarding sociodemographic characteristics and self-perceived oral symptoms were collected using a questionnaire. Periodontal parameters (plaque index, bleeding on probing, probing depth, clinical attachment loss, number of missing teeth, and marginal bone loss) were recorded. RESULTS: There was no significant difference in socioeconomic status, education status, self-perceived oral symptoms, and periodontal parameters among CP patients with and without RA. CONCLUSIONS: Self-perceived oral health and periodontal parameters are mainly governed by the intensity of CP, and the role of RA in this context seems to be rather secondary.
24525913 Hypoxia and STAT3 signalling interactions regulate pro-inflammatory pathways in rheumatoid 2015 Jun OBJECTIVE: To examine the effect of hypoxia on Signal Transducer and Activator of Transcription 3 (STAT3)-induced pro-inflammatory pathways in rheumatoid arthritis (RA). METHODS: Detection of phospho-STAT3 was assessed in RA synovial tissue and fibroblasts (RASFC) by immunohistology/immunofluorescence. Primary RASFCs and a normal synoviocyte cell line (K4IM) were cultured under hypoxic and normoxic conditions±Stat3-siRNA, HIF-siRNA or WP1066 (JAK2-inhibitor). HIF1α, p-STAT3, p-STAT1 and Notch-1IC protein expression were analysed by western blot. Functional mechanisms were quantified by invasion chamber, matrigel and migration assays. IL-6, IL-8, IL-10 and matrixmetalloproteinases (MMP)-3 were quantified by ELISA. Notch-1 receptor, its DLL-4 ligand and downstream target genes (hrt-1, hrt-2) were quantified by real-time PCR. The effect of WP1066 on spontaneous secretion of pro/anti-inflammatory cytokines and Notch signalling was examined in RA synovial explants ex vivo. RESULTS: p-STAT3 was increased in RA synovium compared with control (p<0.05). Hypoxia induced p-STAT3, p-STAT1 and HIF1α expression, an effect blocked by Stat3-siRNA and WP1066. Hypoxia-induced cell invasion, migration and cytokine production were inhibited by Stat3-siRNA (p<0.05) and WP1066 (p<0.05). While HIF1α siRNA inhibited hypoxia-induced p-STAT3 detection, Stat3-siRNA also inhibited hypoxia-induced HIF1α. Furthermore, hypoxia-induced Notch-1IC, DLL4, hrt-1 and -2 expression were significantly inhibited by WP1066 (p<0.05). Finally, in RA synovial explant cultures ex vivo, WP1066 decreased spontaneous secretion of IL-6, IL-8 and MMP3 (p<0.05), Notch-1 mRNA (p<0.05) and induced IL-10 (p<0.05). CONCLUSIONS: This is the first study to provide evidence of a functional link between HIF1α, STAT3 and Notch-1 signalling in the regulation of pro-inflammatory mechanisms in RA, and further supports a role for STAT blockade in the treatment of RA.
26096089 How to investigate new-onset polyarthritis. 2014 Dec Polyarthritis comprises a large number of conditions ranging from rheumatoid arthritis (RA) to metabolic conditions such as ochronosis. Differential diagnosis begins with delineation of inflammatory from non-inflammatory disorders using laboratory markers of inflammation. The latter are good but they can be misleading. Laboratory tests help in the diagnosis of rheumatic diseases as well as their prognostication. The choice of serological tests should be based on clinical differential diagnosis and not 'arthritis panels'. The point of time when the test is performed in the clinical course of disease can have an important influence on the result obtained. Anti-citrullinated protein antibody (ACPA), rheumatoid factor, human leucocyte antigen (HLA) B27 and imaging are routinely employed for the early diagnosis of RA and spondyloarthritis (SpA). Despite advances in musculoskeletal imaging modalities such as ultrasonography (USG) with power Doppler, conventional as well as extremity magnetic resonance imaging (MRI) and dual-energy computed tomography (DECT), their exact place in clinical rheumatology remains to be defined. Synovial fluid examination has only a limited role in the investigations of new-onset polyarthritis.
24321457 A single nucleotide polymorphism of TRAF1 predicts the clinical response to anti-TNF treat 2014 Mar OBJECTIVES: Recent genome-wide association studies disclosed that several single nucleotide polymorphisms (SNPs), including tumour necrosis factor (TNF) receptor-associated factor 1 (TRAF1) (+16860A/G), are associated with the pathophysiology of rheumatoid arthritis (RA). We assessed the usefulness of TRAF1 genotyping as a genetic predictor of the response to anti-TNF treatment in Japanese RA patients. METHODS: TRAF1 (+16860A/G) was genotyped using the TaqMan SNP genotyping assay in 101 Japanese RA patients treated with anti-TNF drugs for >24 weeks. We retrospectively analysed the association between SNP and the clinical response to treatment. TRAF1 mRNA and protein expression was also evaluated in CD4+, CD8+, CD14+, or CD19+ cells from 25 healthy subjects using quantitative polymerase chain reaction and intracellular staining flow cytometry, respectively. RESULTS: No statistical difference in DAS28-ESR at baseline was observed between the patient groups with the AA, AG, or GG genotype. The GG genotype was more frequent in non-responders than in good or moderate responders [odds ratio (OR) 7.4, 95% confidence interval (CI) 1.5-37.5]. The non-responders possessed the G allele more frequently than the good or moderate responders (OR 3.5, 95% CI 1.4-9.0). TRAF1 protein expression increased significantly in CD14+ monocytes from healthy subjects with the GG genotype compared with that in subjects with the AA or AG genotype. CONCLUSIONS: TRAF1 (+16860A/G) may be useful for predicting the clinical response to anti-TNF treatment and may contribute to resistance to treatment in RA patients with the GG genotype by increasing the TRAF1 expression in circulating inflammatory cells.
23244209 A decrease in galectin-1 (Gal-1) levels correlates with an increase in anti-Gal-1 antibodi 2013 BACKGROUND: Several studies have confirmed that galectin-1 (Gal-1) plays a role in controlling the immune response because of its pro-apoptotic effect. Although studies based on a rheumatoid arthritis (RA) mouse model have suggested a crucial role for Gal-1 in inflammation, clinical data are lacking. We have detected the presence of autoantibodies against galectins in blood, but their physiological meaning remains unknown. OBJECTIVES: To compare plasma and synovial levels of Gal-1 in RA patients and in healthy controls, and correlate them with clinical parameters. METHODS: Plasma and synovial (non-arthritic knee effusion) samples were collected from RA patients and healthy donors. All patients were receiving treatment with steroids and/or disease-modifying anti-rheumatic drugs (DMARDs). A blood sample was taken at a baseline visit to determine plasma anti-cyclic citrullinated peptide (anti-CCP) antibodies, tumour necrosis factor alpha (TNF-α), Gal-1, and anti-Gal-1 autoantibodies. RESULTS: Although plasma levels of Gal-1 were similar in patients and controls, the concentration of Gal-1 was significantly reduced in the synovial fluid of patients with RA. This reduction was not correlated with TNF-α or C-reactive protein (CRP) levels. However, the decrease in synovial Gal-1 correlated with a significant increase in anti-Gal-1 autoantibodies and anti-CCP antibody titres, suggesting a physiological effect of autoantibodies limiting the amount Gal-1 and potentially blocking its biological effect in RA patients. CONCLUSION: Gal-1 levels were significant reduced at the synovial level in RA patients, possibly as a consequence of the increase in anti-Gal-1 autoantibodies.
24392804 Circulating Th17 and Th1 cells expressing CD161 are associated with disease activity in rh 2014 OBJECTIVES: To determine whether the percentages of major CD4+CD161+ T-cell subsets [T-helper (Th)17, Th1, and Th17/Th1] in peripheral blood are correlated with disease activity of rheumatoid arthritis (RA). METHOD: In 42 RA patients and 15 healthy controls (HCs), the percentages of interleukin (IL)-17- and/or interferon (IFN)-γ-producing CD4+CD161+ T cells and the plasma levels of related cytokines were assessed by flow cytometry and cytometric bead array (CBA) analysis, respectively. Disease activity was evaluated by the 28-joint Disease Activity Score (DAS28). RESULTS: The percentage of circulating CD4+CD161+IL-17+IFN-γ- T cells (CD161+ Th17) in RA patients increased significantly and was higher in patients with active disease status (DAS28 > 3.2) compared with those with low disease status (DAS28 ≤ 3.2), and correlated positively with DAS28, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), IL-17, and IL-6 levels in RA patients. The percentage of circulating CD4+CD161+IL-17-IFN-γ+ T cells (CD161+ Th1) decreased and correlated negatively with DAS28, CRP, and ESR levels in RA patients, while the percentage of CD4+CD161+IL-17+IFN-γ+ T cells (CD161+ Th17/Th1) was unchanged in RA patients and was not correlated with RA disease activity. CONCLUSIONS: These data suggest that the percentages of circulating CD161+ Th17 and CD161+ Th1 cells in RA patients reflect the degree of disease activity. They support the hypothesis that Th17 cells are involved in the pathogenesis of RA and that CD161+ Th17/CD161+ Th1-cell imbalance may contribute to the development of RA.
24722995 PBMC and exosome-derived Hotair is a critical regulator and potent marker for rheumatoid a 2015 Feb Despite growing importance of long non-coding RNAs (lncRNAs) in normal physiological and disease conditions, our knowledge of RA-related lncRNAs remains limited. Therefore, we aimed to identify lncRNA signatures that have prognostic values in RA. There was a notably high expression level of Hotair in blood mononuclear cells and serum exosome of rheumatoid arthritis (RA) patients, leading the migration of active macrophage. In contrast, markedly lower level of Hotair was detected in differentiated osteoclasts and rheumatoid synoviocytes and enforced expression of Hotair led to significantly decreased levels of MMP-2 and MMP-13. This exploratory study provides novel empirical evidence that Hotair could be one of potential biomarkers for diagnosing RA.
24585544 Secreted semaphorin 5A activates immune effector cells and is a biomarker for rheumatoid a 2014 Jun OBJECTIVE: To investigate the role of the multifunctional protein semaphorin 5A (Sema5A) in modulating cellular immune responses and as a biomarker in rheumatoid arthritis (RA). METHODS: A soluble form of recombinant Sema5A was used to assess its effect on the functions of primary T cells and natural killer (NK) cells isolated from the peripheral blood of healthy donors. Cell proliferation and expression of transcription factors were determined by flow cytometry. Cytokine secretion was analyzed using Luminex technology. Serum samples obtained from 145 patients with RA and control serum samples obtained from healthy individuals or patients with non-RA rheumatic diseases were analyzed for the presence of secreted Sema5A, using enzyme-linked immunosorbent assays and immunoblotting. RESULTS: Soluble Sema5A strongly increased T cell and NK cell proliferation and induced the secretion of proinflammatory Th1/Th17 cytokines. Accordingly, Sema5A stimulation caused significant up-regulation of T-bet and retinoic acid receptor-related orphan nuclear receptor γt levels in T cells. In addition, significantly elevated levels of secreted Sema5A were detected in the serum of patients with RA compared with control serum. Sema5A levels were highest in patients with RA who were positive for the RA biomarker anti-cyclic citrullinated peptide (P < 0.001 versus patients with systemic lupus erythematosus and patients with Sjögren's syndrome) and correlated with the levels of rheumatoid factor. CONCLUSION: Soluble Sema5A is a potent activator of T cells and NK cells in vitro, and high serum levels of Sema5A are associated with RA. Taken together, the results indicate that Sema5A contributes to the pathogenesis of RA through antigen-independent T cell and NK cell activation. Hence, Sema5A is a promising complementary biomarker for the diagnosis of RA.
24861760 Determination of 4-hydroxy-2-nonenal in serum by high-performance liquid chromatography wi 2014 Jun 4-Hydroxy-2-nonenal (4HNE) is a major aldehyde generated during lipid peroxidation. The clinical monitoring of 4HNE in biological fluids could be useful for the early diagnosis of several diseases involving lipid peroxidation, such as rheumatoid arthritis, Parkinson's disease and cancer. In this study, an HPLC with fluorescence detection method was developed for the determination of 4HNE in human serum. The proposed method involves the extraction of 4HNE from human serum by subzero temperature extraction and fluorescent labeling of 4HNE with 4-(N,N-dimethylaminosulfonyl)-7-hydrazino-2,1,3-benzoxadiazole. The lower detection limit (signal-to-noise ratio=3) of the method was 0.06 µm in serum. The proposed method was successfully applied to the measurement of 4HNE in sera obtained from patients with rheumatoid arthritis.
23446460 [Magnetic resonance tomography and hybrid imaging in rheumatology]. 2013 Mar In rheumatologic diseases magnet resonance imaging (MRI) is capable of depicting early inflammatory changes which are frequently missed by other imaging modalities. New MRI protocols and hardware, primarily whole-body MRI and low-field extremity MRI facilitate the use of MRI in rheumatology patients. The increasing number of functional MRI techniques provide additional molecular information on the tissue composition, e.g. cartilage quality. These molecular MRI techniques enable new ways for early disease detection and therapy monitoring. Hybrid imaging modalities, such as MRI-SPECT (single photon mmission tomography) and MRI-PET (positron emission tomography) provide a new level of molecular imaging in rheumatology by adding the advantages of the combined modalities. This article provides an up-to-date overview of new MRI techniques and innovative hybrid imaging modalities and summarizes the first available results of these procedures in rheumatologic applications.
23418046 Effects of subcutaneous and intravenous golimumab on inflammatory biomarkers in patients w 2013 Jul OBJECTIVE: To evaluate the effects of the anti-TNF-α monoclonal antibody golimumab, administered by s.c. injection or i.v. infusion, on markers of inflammation in patients with RA. METHODS: In this phase 1, open-label study, patients with active RA were randomized to receive s.c. golimumab 100 mg at baseline and every 4 weeks through week 20 (n = 33; group 1) or i.v. golimumab 2 mg/kg at baseline and week 12 (n = 16; group 2). Serum levels of CRP, IL-6, serum amyloid A (SAA), TNF receptor II (TNFRII), MMP-3, hyaluronic acid, haptoglobin, ferritin and haemoglobin and serum/urine hepcidin were measured at various time points. Associations between the biomarkers were assessed with Spearman's correlations. RESULTS: In both groups 1 and 2, decreases in mean serum levels of CRP, IL-6, SAA, TNFRII, MMP-3, haptoglobin, ferritin and hepcidin, and mean urine levels of hepcidin occurred within 1 week and were sustained through week 8. Decreases in concentrations of serum CRP, IL-6, SAA, MMP-3, hepcidin, ferritin and haptoglobin and urine hepcidin were maintained through week 24 in group 1, but began to reverse after week 8 in group 2. Among all patients, decreases in serum hepcidin correlated significantly with decreases in serum CRP and ferritin. CONCLUSION: Decreases in serum and urine concentrations of markers of inflammation occurred as early as 24 h after treatment with golimumab, and most of these improvements were sustained through week 24 in group 1.
24989017 Clinical and laboratory features of overlap syndromes of idiopathic inflammatory myopathie 2014 Aug Because overlap syndromes (OSs) are rarely described, we analyzed retrospectively their frequencies and correlations in Brazilian series of 31 patients with dermatomyositis (DM)/polymyositis (PM) associated with systemic lupus erythematosus (SLE), systemic sclerosis (SSc), or rheumatoid arthritis (RA) attended at a referral single center. Myositis-specific autoantibodies (MSAs: anti-Jo-1, anti-PL-7, anti-PL-12, anti-EJ, anti-OJ, anti-SRP, anti-Mi-2) and myositis-associated autoantibodies (MAAs: anti-PM-Scl75, anti-PM-Scl100, anti-Ku) as well as specific autoantibodies related to SLE, SSc, and RA were investigated. The mean age of the OS patients (9 DM and 22 PM) was 44.6 ± 15.4 years, with a predominance of women (83.9 %) and white ethnicity (58.1 %). PM was the most frequent inflammatory myopathy, and the clinical presentation of DM/PM was significantly different among the OS groups. Overlap was found with SSc (48.4 %), SLE (29.0 %), and RA (22.6 %). The clinical manifestations of DM/PM were identified simultaneously with SSc and RA in the majority of cases, in contrast to identification in the SLE group (p < 0.05). All patients were positive for antinuclear antibodies, and the prevalence of MSA and MAA was 38.8 % in all OS groups, mutually exclusive, and more frequent in the SSc group. Comparing the clinical and laboratory features, there was a higher frequency of vascular (skin ulcers, Raynaud's phenomenon) and pulmonary (interstitial lung disease) involvement in the SSc group (p < 0.05). Moreover, there were no differences among the groups in relation to disease relapse and deaths. Concluding, this is the first study to show the different characteristics of a series of patients with connective tissue disease (CTD)-OS in the heterogeneous Brazilian population.
23425151 Comparison of methodologies for analysing the progression of joint destruction in rheumato 2013 OBJECTIVES: Progression of joint destruction is an important phenotypic feature in rheumatoid arthritis (RA). When factors have small effect sizes, both the avoidance of phenotypic misclassification and discerning true effects from noise are challenging. Assembling radiological measurements repeatedly in time harbours a smaller risk of misclassification than single measurements. Given serial measurements, different methods of analysis can be applied. This study evaluates different statistical methods of analysing longitudinal data. METHODS: Three statistical methods were studied: linear regression (LR), generalized estimating equations (GEE), and multivariate normal regression analysis (MRA). All were applied longitudinally, testing for differences in radiological progression rates. As genetic variants are known to have small effect sizes, two genetic variants were studied as examples: rs675520 (located in the TNFAIP3-OLIG3 region) and the presence of the human leucocyte antigen (HLA) shared epitope (SE) alleles. Radiological data for 602 early RA patients with yearly radiographs and 7-years of follow-up were used. The powers obtained with the methods and the robustness against missingness were evaluated as outcome measures. RESULTS: The presence of the rs675520 polymorphism and the HLA-SE risk genotype was associated with a 0.65-0.77 and 1.17-1.51 fold increased rate of joint destruction, respectively. The analyses performed with MRA resulted in smaller 95% confidence intervals (CIs) than the analyses using LR or GEE. In addition, the 95% CIs increased with the number of radiographs per patient. The power of MRA was higher than that of GEE. MRA was more robust against selective missingness than GEE or LR with a two-step approach (LR(ts)). CONCLUSIONS: A multivariate normal regression model on subsequent radiographs is a powerful and robust method for analysing longitudinal joint destruction data.
24971392 Methotrexate-associated nonalcoholic fatty liver disease with transaminitis in rheumatoid 2014 BACKGROUND: The aim of this study was to determine the risk factors of MTX-associated nonalcoholic fatty liver disease (NAFLD) with transaminitis in a cohort of rheumatoid arthritis (RA) patients from Singapore. METHODS: Patients who developed ultrasound proven NAFLD with transaminitis while on MTX therapy were identified. The demographic and clinical characteristics of the above patients (cases) were compiled and compared with age- and gender-matched controls who were RA patients on long standing MTX therapy without any episode of transaminitis. RESULTS: Among the 978 patients who had received MTX, the prevalence of MTX-associated NAFLD was 4.7% (46 patients). Compared to the controls, the cases had significantly higher mean cumulative dose of MTX (4.03 ± 2.25 g versus 10.04 ± 9.94 g, P ≤ 0.05), weekly dose of MTX (11.3 ± 4.8 mg versus 13.1 ± 4.4 mg weekly, P = 0.033), and fasting blood glucose (P = 0.029). Following multivariate regression analysis, only cumulative dose of MTX remained significant (P = 0.015). Among the cases, the cumulative dose of MTX was found to have a significant positive correlation with the alanine transaminase (ALT) level (P < 0.05, standardised beta coefficient 0.512). CONCLUSION: The cumulative dose of MTX was the only independent predictor of MTX-associated NAFLD with transaminitis.
23537298 Study of association between HLA-DR4 and DR53 and autoantibody detection in rheumatoid art 2013 The present study explored the association between human leukocyte antigen (HLA)-DR4, DR53, and auto antibodies in rheumatoid arthritis (RA) and its clinical significance. A total of 305 patients with RA and 50 healthy subjects who underwent medical examination were evaluated. HLA-DR4 and HLA-DR53 and auto antibodies were detected. The results showed that frequencies of HLA-DR4 and HLA-DR53 alleles in RA patients were 42.95% and 54.75%, respectively, which were significantly different from those in control group (p < 0.01). Frequencies of anti-cyclic citrullinated peptide antibody (CCP), anti-RA33, anti-keratin antibody (AKA), and anti-nuclear antibody (ANA) in RA patients (n = 305) were 72.13%, 36.39%, 44.92%, and 60.98%, respectively. Results of rheumatoid factor (RF) and C-reactive protein (CRP) were 148.29 ± 391.01 IU/mL and 18.14 ± 26.87 mg/L, respectively, which were significantly different from those in control group (p < 0.01, t-test). The results indicated that the HLA- DR4 gene was clearly associated with susceptibility of RA. Combined detection of related auto antibodies might improve diagnosis rate of RA significantly, and the positive rate was higher than that for a single antibody.
22903282 Postoperative alignment and ROM affect patient satisfaction after TKA. 2013 Jan BACKGROUND: Patient satisfaction has increasingly been recognized as an important measure after total knee arthroplasty (TKA). However, we do not know yet how and why the patients are satisfied or dissatisfied with TKA. QUESTIONS/PURPOSES: We asked: (1) After TKA, how satisfied are patients and which activities were they able to do? (2) Are patient-derived scores related to physician-derived scores? (3) Which factors affect patient satisfaction and function? METHODS: We retrospectively evaluated 375 patients who had undergone 500 TKAs between February 22, 2000 and December 1, 2009. We sent a questionnaire for The 2011 Knee Society Knee Scoring System to the patients. We determined the correlation of patient- and physician-derived scores and factors relating to the five questions relating to satisfaction and the 19 questions relating function. The minimum followup was 2 years (mean, 5 years; range, 2-11 years). RESULTS: The mean score for symptoms was 19 (74%), 23 (59%) for patient satisfaction, 10 (64%) for patient expectations, and 53 (53%) for functional activities. We found a poor correlation between the patient-derived and the physician-derived scores. Old age and varus postoperative alignment negatively correlated with the satisfaction. Varus alignment and limited range of motion (ROM) negatively correlated with the expectation. Old age, rheumatoid arthritis, and limited ROM negatively correlated with the functional activities. CONCLUSIONS: Most patients did not report symptoms, but they experienced difficulty with activities of daily living after TKA. Patient satisfaction is difficult to measure, but avoiding varus alignment and achieving better ROM appear to be important for increasing satisfaction and meeting expectations.
23670331 Laryngeal involvement in rheumatoid arthritis. 2013 Mar The prevalence of laryngeal involvement in Rheumatoid Arthritis (RA) ranges from 13 to 75%. The specific RA manifestations include the cricoarytenoid arthritis and the presence of rheumatoid nodules in the vocal folds. OBJECTIVE: The objective of this study is to evaluate the prevalence of dysphonia and laryngeal alterations on videolaryngoscopy in RA patients and their association with disease activity. METHOD: This is a clinical cross-sectional study that evaluated patients with rheumatoid arthritis as to their disease activity score in 28 joints (DAS-28), laryngeal symptoms, application of a Portuguese version of the Voice Handicap Index and videolaryngoscopy findings, comparing them with a control group. RESULTS: We evaluated 47 (54%) patients with rheumatoid arthritis and 40 (46%) controls. The prevalence of dysphonia and videolaryngoscopy changes was respectively 12.8% and 72.4% in patients with RA. The mean of DAS-28 was 3.3 ± 1.2; 26 (74.3%) of 35 patients presenting active disease had laryngeal changes (p = 0.713). Posterior laryngitis was the most common diagnosis (44.7%). CONCLUSION: The prevalence of laryngeal disorders in RA patients was 72.4% and the prevalence of dysphonia was 12.8%. There was no significant relationship between laryngeal disorders and disease activity.
24404820 Self-assessment tool of disease activity of rheumatoid arthritis by using a smartphone app 2014 Mar OBJECTIVES: The disease activities of rheumatoid arthritis (RA) tend to fluctuate between visits to doctors, and a self-assessment tool can help patients accommodate to their current status at home. The aim of the present study was to develop a novel modality to assess the disease activity of RA by a smartphone without the need to visit a doctor. SUBJECTS AND METHODS: This study included 65 patients with RA, 63.1 ± 11.9 years of age. The 28-joint disease activity score (DAS28) was measured for all participants at each clinic visit. The patients assessed their status with the modified Health Assessment Questionnaire (mHAQ), a self-assessed tender joint count (sTJC), and a self-assessed swollen joint count (sSJC) in a smartphone application. The patients' trunk acceleration while walking was also measured with a smartphone application. The peak frequency, autocorrelation (AC) peak, and coefficient of variance of the acceleration peak intervals were calculated as the gait parameters. RESULTS: Univariate analyses showed that the DAS28 was associated with mHAQ, sTJC, sSJC, and AC (p<0.05). In a stepwise linear regression analysis, mHAQ (β = 0.264, p<0.05), sTJC (β = 0.581, p<0.001), and AC (β = -0.157, p<0.05) were significantly associated with DAS28 in the final model, and the predictive model explained 67% of the DAS28 variance. CONCLUSIONS: The results suggest that noninvasive self-assessment of a combination of joint symptoms, limitations of daily activities, and walking ability can adequately predict disease activity of RA with a smartphone application.
25498120 A circulating reservoir of pathogenic-like CD4+ T cells shares a genetic and phenotypic si 2016 Feb OBJECTIVES: Systemic immunological processes are profoundly shaped by the micro-environments where antigen recognition occurs. Identifying molecular signatures distinctive of such processes is pivotal to understand pathogenic immune responses and manipulate them for therapeutic purposes. Unfortunately, direct investigation of peripheral tissues, enriched in pathogenic T cells, is often impossible or imposingly invasive in humans. Conversely, blood is easily accessible, but pathogenic signatures are diluted systemically as a result of the strict compartmentalisation of immune responses. In this work, we aimed at defining immune mediators shared between the bloodstream and the synovial micro-environment, and relevant for disease activity in autoimmune arthritis. METHODS: CD4(+) T cells from blood and synovium of patients with juvenile idiopathic arthritis (JIA) were immunophenotyped by flow cytometry. The TCR repertoire of a circulating subset showing similarity with the synovium was analysed through next-generation sequencing of TCR β-chain CDR3 to confirm enrichment in synovial clonotypes. Finally, clinical relevance was established by monitoring the size of this subset in the blood of patients with JIA and rheumatoid arthritis (RA). RESULTS: We identified a small subset of circulating CD4(+) T cells replicating the phenotypical signature of lymphocytes infiltrating the inflamed synovium. These circulating pathogenic-like lymphocytes (CPLs) were enriched in synovial clonotypes and they exhibited strong production of pro-inflammatory cytokines. Importantly, CPLs were expanded in patients with JIA, who did not respond to therapy, and also correlated with disease activity in patients with RA. CONCLUSIONS: CPLs provide an accessible reservoir of pathogenic cells recirculating into the bloodstream and correlating with disease activity, to be exploited for diagnostic and research purposes.