Browse

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

ID PMID Title PublicationDate abstract
27941198 [Clinical and ultrasound assessment of the disease activity in patients with rheumatoid ar 2016 INTRODUCTION: Rheumatoid arthritis (RA) is a chronic, systemic, inflammatory disease, leading to irreversible joint destruction and deformities. The adequate assessment of the disease activity enables the correct choice of therapy and evaluation of the treatment efficacy. The aim of the study was to compare different methods of assessment of the disease activity, using clinical data and ultrasonography (US) of joints, in patients with RA, in daily clinical practice. MATERIAL AND METHODS: The study group consisted of 68 patients with RA. The clinical assessment of the disease activity was performed using the Disease Activity Score based on evaluation of 28 joints (DAS28). Ultrasonography (US) examination of joints was performed in 24 small joints, evaluating hypertrophy and vascularity of the synovium. Ability to perform daily activities was measured using the modified Health Assessment Questionnaire (M-HAQ) Results: There were statistically significant correlations between the grade of synovial vascularity of joints and parameters of clinical activity [tender joints count (TJC), swollen joints count (SJC), DAS28] and laboratory acute phase parameters (ESR, CRP). The grade of synovial hypertrophy was significantly associated with SJC and DAS28, and not with laboratory parameters. M-HAQ value was significantly associated only with TJC. CONCLUSIONS: In RA patients an assessment of the disease activity should be performed taking into consideration several parameters, clinical activity, laboratory parameters, US and quality of life assessment. US examination enables verification of synovial inflammatory activity, which is not always possible in clinical examination.
27613480 Trikatu, an herbal compound ameliorates rheumatoid arthritis by the suppression of inflamm 2016 Oct 25 The present study was designed to investigate the potential therapeutic effect of trikatu, an herbal compound and its underlying molecular mechanism in rats with adjuvant-induced arthritis (AIA). Our results indicate that trikatu (1000 mg/kg/b.wt. oral) administration suppressed the production of pro-inflammatory cytokines (tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, and monocyte chemoattractant protein (MCP)-1) and downregulated the mRNA expression levels of inflammatory mediators (TNF-α, IL-1β, IL-6, IL-17, MCP-1, receptor activator of nuclear factor kappa B ligand (RANKL), cyclooxygenase (COX)-2, and inducible nitric oxide synthase (iNOS)) and transcription factors (nuclear factor kappa B 65 (NFкB-p65) and activator protein-1 (AP-1)) in cultured AIA-fibroblast like synoviocytes and synovial tissue of AIA rats. Consistently, the protein expression of NFкB-p65, IL-17, TNF-α, COX-2, and RANKL was also dramatically reduced in cultured AIA-fibroblast like synoviocytes and synovial tissue of AIA rats by trikatu treatment. In addition, trikatu suppressed the expression and phosphorylation of NFкB-p65 similar to the Bay 11-7082 (NFкB inhibitor) in cultured AIA-fibroblast like synoviocytes. Furthermore, trikatu alleviated the histopathology of joint of arthritic rats. Overall, these data highlights that trikatu could be a promising alternative modality for the possible treatment of rheumatoid arthritis and other inflammatory diseases.
26242858 Can the publication of guidelines change the management of early rheumatoid arthritis? An 2015 Dec OBJECTIVE: To assess whether publication of national treatment guidelines improved the management of early RA in the UK. METHODS: Incident diagnoses of RA in persons aged over 18 years from 1995 to 2010 were identified from the Clinical Practice Research Datalink. Using a natural experimental study design, interrupted time series analysis was used to assess whether trends in the proportion of patients receiving DMARDs, within 3 and 12 months of diagnosis, changed following publication of British Society for Rheumatology guidelines in 2006. RESULTS: Between 1995 and 2010, 11 772 incident cases of RA were identified. There was a progressive increase in the proportion of patients prescribed any DMARD within 12 months from 43.3% in 1995 to 78.5% in 2010. After publication of the British Society for Rheumatology guidelines, the proportion of patients prescribed any DMARD within 12 months increased by 4.2% (P = 0.053). Prior to the guidance, prescribing was increasing by 1.64% per year, compared with 3.55% per year after publication (P < 0.001). CONCLUSION: Guidelines published by a national body can improve the proportion of patients receiving DMARD treatment in the first year after diagnosis of RA.
26147000 Energy Metabolism Disorder as a Contributing Factor of Rheumatoid Arthritis: A Comparative 2015 OBJECTIVES: To explore the pathogenesis of rheumatoid arthritis (RA), the different metabolites were screened in synovial fluid by metabolomics. METHODS: Synovial fluid from 25 RA patients and 10 normal subjects were analyzed by GC/TOF MS analysis so as to give a broad overview of synovial fluid metabolites. The metabolic profiles of RA patients and normal subjects were compared using multivariate statistical analysis. Different proteins were verified by qPCR and western blot. Different metabolites were verified by colorimetric assay kit in 25 inactive RA patients, 25 active RA patients and 20 normal subjects. The influence of hypoxia-inducible factor (HIF)-1α pathway on catabolism was detected by HIF-1α knockdown. RESULTS: A subset of 58 metabolites was identified, in which the concentrations of 7 metabolites related to energy metabolism were significantly different as shown by importance in the projection (VIP) (VIP ≥ 1) and Student's t-test (p<0.05). In the 7 metabolites, the concentration of glucose was decreased, and the concentration of lactic acid was increased in the synovial fluid of RA patients than normal subjects verified by colorimetric assay Kit. Receiver operator characteristic (ROC) analysis shows that the concentration of glucose and lactic acid in synovial fluid could be used as dependable biomarkers for the diagnosis of active RA, provided an AUC of 0.906 and 0.922. Sensitivity and specificity, which were determined by cut-off points, reached 84% and 96% in sensitivity and 95% and 85% in specificity, respectively. The verification of different proteins identified in our previous proteomic study shows that the enzymes of anaerobic catabolism were up-regulated (PFKP and LDHA), and the enzymes of aerobic oxidation and fatty acid oxidation were down-regulated (CS, DLST, PGD, ACSL4, ACADVL and HADHA) in RA patients. The expression of HIF-1α and the enzymes of aerobic oxidation and fatty acid oxidation were decreased and the enzymes of anaerobic catabolism were increased in FLS cells after HIF-1α knockdown. CONCLUSION: It was found that enhanced anaerobic catabolism and reduced aerobic oxidation regulated by HIF pathway are newly recognized factors contributing to the progression of RA, and low glucose and high lactic acid concentration in synovial fluid may be the potential biomarker of RA.
27532459 The effectiveness of acupuncture on pain, physical function and health-related quality of 2016 May The objective of this review is to identify and synthesize the best available evidence on the effectiveness of acupuncture on pain, physical function and health-related quality of life in patients with rheumatoid arthritis.More specifically, the review questions are:• Is acupuncture effective in improving health-related quality of life in patients with RA?• Is acupuncture effective in relieving pain in patients with RA?• Is acupuncture effective in improving physical function in patients with RA?
25399339 Factors influencing ultrasonographic remission in patients with rheumatoid arthritis. 2015 Mar The aim of this study was to define the ultrasonographic factors that indicate clinical remission in patients with RA. We enrolled a cohort of patients with RA in whom the disease had been in remission for at least 6 months. Musculoskeletal ultrasound (US) examination was used to evaluate the status of active synovitis, power Doppler (PD) signalling, and synovitis in the bilateral metacarpophalangeal; proximal interphalangeal; and radiocarpal, ulnocarpal, and intercarpal, compartments of the wrist. A total of 64 RA patients with a mean disease duration of 79.97 months were studied. Of all patients, 36% had ultrasonographic synovitis and 29% an increased PD signal from at least one joint. Delay in diagnosis was highly correlated with synovitis and PD synovitis (r = 0.55, p = 0.000; and r = 0.51, p = 0.001, respectively). A weak negative correlation was evident between synovitis, PD synovitis, tenosynovitis, PD tenosynovitis, and duration of clinical remission (respectively, r = -0.426, p = 0.000; r = -0.333, p = 0.007; r = -0.243, p = 0.050; and r = -0.247, p = 0.049). Upon multivariate logistic regression analysis, the duration of clinical remission and delay in diagnosis were the factors that most influenced ultrasonographic remission (OR 3.46, p = 0.046; OR 3.27, p = 0.016, respectively). Synovial inflammation may persist in RA patients exhibiting clinical remission. We found that US detected subclinical synovitis. The most important factors preventing ultrasonographic remission were a short duration of clinical remission and delay in diagnosis.
26091907 Validity of early MRI structural damage end points and potential impact on clinical trial 2016 Jun OBJECTIVE: To evaluate the construct validity of the rheumatoid arthritis MRI score (RAMRIS) erosion evaluation as structural damage end point and to assess the potential impact of incorporation in clinical trials. METHODS: In a randomised trial of early methotrexate-naïve RA (GO-BEFORE), RAMRIS scores were determined from MRIs and van der Heijde-Sharp (vdHS) scores from radiographs, at baseline, week 12, week 24 and week 52. Progression in damage scores was defined as change >0.5. Associations of X-ray and MRI outcomes with clinical features were evaluated for convergent validity. Iterative Wilcoxon rank sum tests and tests of proportion estimated the sample size required to detect differences between combination therapy (methotrexate+golimumab) and methotrexate-monotherapy arms in (A) change in damage score and (B) proportion of patients progressing. RESULTS: Patients with early MRI progression had higher DAS28, C reactive protein (CRP) and vdHS at baseline, and higher 2-year HAQ. Associations were similar to those with 1-year vdHS progression. Differences in change in structural damage between treatment arms achieved significance with fewer subjects when 12-week or 24-week MRI erosion score was the outcome (150 patients; 100 among an enriched sample with baseline-synovitis >5) compared with the 52-week vdHS (275 patients). Differences in the proportion progressing could be detected in 234 total subjects with 12-week MRI in an enriched sample whereas 1-year X-ray required between 468 and 1160 subjects. CONCLUSIONS: Early MRI erosion progression is a valid measure of structural damage that could substantially decrease sample size and study duration if used as structural damage end point in RA clinical trials.
27311195 [Rheumatoid arthritis and malignancy]. 2016 Jun Rheumatoid arthritis (RA) is associated with excess mortality. Especially, malignancy is a major cause of mortality. According to previous reports, the overall incidence of malignancies in RA patients has been reported to be comparable or slightly higher than that in general population. The increased incidence of malignant lymphoma and lung cancer has been reported to be consistent in most studies. The use of some csDMARD was also reported as risk factors for malignancy. Recently, MTX associated lymphoproliferative disorder(MTX-LPD) is one of the important complications in RA treatment. We revealed the mean MTX dose was demonstrated to be an independent risk factor regarding MTX-LPD onset in RA patients. This data suggest that the treatment with higher MTX dose promotes LPD onset in Japanese RA patients.
27828847 Increased risk of vertebral fracture in patients with rheumatoid arthritis: A meta-analysi 2016 Nov The relationship between rheumatoid arthritis and risk of vertebral fracture has been reported by several observational studies. However, there is no higher-level evidence study, such as meta-analysis, that has investigated the relationship, and its mechanisms are not yet fully clear. This meta-analysis aimed to provide a summary of an observational study of the relationship between rheumatoid arthritis and the risk of vertebral fractures.Relevant studies were identified by searching PubMed and EMBASE databases (up to August 1, 2016). We included published observational studies (cohort or case-control design) evaluating the relationship between rheumatoid arthritis and the risk of vertebral fractures. Two reviewers searched and abstracted the data independently. Relative risks (RRs) with 95% confidence intervals (CIs) were used throughout the whole analysis.Seven observational studies (2 cohort studies, 2 nested case-control studies, and 3 case-control studies) were included in this meta-analysis. The results showed that the pooled RR of vertebral fracture for individuals with rheumatoid arthritis was 2.34 (95% CI 2.05-2.63, I = 35.4%, P for heterogeneity = 0.16). Further subgroup analysis by sex showed that the pooled RRs for both women and men, and only women were 2.14 (95% CI 1.47-2.8, I = 48.5%, P for heterogeneity = 0.12) and 2.39 (95% CI 2.07-2.70, I = 34%, P for heterogeneity = 0.22), respectively. Subgroup analysis by study design showed that the pooled RRs for cohort studies, nested case-control studies, and case-control studies were 2.31 (95% CI 1.95-2.67, I = 4.8%, P for heterogeneity = 0.31), 1.89 (95% CI 1.01-2.77, I = 72.1%, P for heterogeneity = 0.06), and 2.62 (95% CI 2.04-3.91, I = 26.1%, P for heterogeneity = 0.26), respectively.Based on our meta-analysis, rheumatoid arthritis should be regarded as an independent risk factor of vertebral fracture. Further studies are needed to institute prevention and treatment strategies.
28006881 Methotrexate-induced panniculitis in a patient with rheumatoid arthritis. 2016 Dec Methotrexate-induced accelerated nodulosis (MIAN) is not an uncommon adverse effect associated with the use of the methotrexate in rheumatoid arthritis. Limited case reports describe panniculitis as a pathological finding in this setting. A 31-year-old female with seropositive rheumatoid arthritis on methotrexate therapy presented with a 2-week history of sudden onset of painful infiltrated subcutaneous nodules on both forearms. Based on clinical and histological findings, a diagnosis of methotrexate-induced panniculitis was made. The majority of MIAN case reports that we reviewed showed characteristic pathological findings of classic rheumatoid nodules; few reported panniculitis as a finding. This case illustrates the importance of recognizing this phenomenon as methotrexate-induced panniculitis should be considered in the differential diagnosis of any patient receiving methotrexate presenting with a recent history of accelerated nodulosis. Discontinuation of methotrexate remains controversial.
27468889 Evaluating the consequences of rheumatoid arthritis. 2017 Jul Patients and non-patients tend to attach different utility values to the state of suffering from specific illnesses. This observation naturally leads to the question whose utility values should be used as the basis in cost-effectiveness analysis (CEA). Intuitively, one would presume that patients are better informed about the consequences of their illness, and public authorities should, therefore, use the patients' utility values in CEA. Contrary to this presumption, it has been argued that society at large should determine which values are to be used and not the patients because, in the end, it is societal resources that are to be allocated. Against this background, we use data from a discrete choice experiment (DCE) that was completed by patients of rheumatoid arthritis (RA) and non-patients to explore the discrepancies between the two groups' utility estimates for typical consequences of RA. Our results indicate that both groups attach remarkably similar part-worth utilities to the symptoms pain, fatigue, and functional limitations. However, non-patients significantly undervalue the ability to work when compared to patients.
26415740 Prevalence of soluble peptidylarginine deiminase 4 (PAD4) and anti-PAD4 antibodies in auto 2016 May The objectives of this study are to investigate the prevalence of PAD4 and anti-PAD4 antibodies (Abs) in autoimmune diseases and to clarify their association with anticitrullinated protein antibodies (ACPAs) and shared epitope (SE) in patients with rheumatoid arthritis (RA). Levels of human PAD4 and anti-PAD4 Abs in serum or plasma were measured using sandwich ELISA. Samples were obtained from patients with RA (n = 148), SLE (n = 36), or SS (n = 37) and from healthy controls (HCs; n = 40). Antibodies against cyclic citrullinated glucose-6-phosphate isomerase (GPI) (CCG)-2, CCG-7, anti-CEP-1, and anti-CCP Abs were also measured using ELISA. Patients with RA were genotyped for HLA-DRB1. The human PAD4 and anti-PAD4 Ab levels were compared with the ACPA and SE in patients with RA. The PAD4 levels were 111.9 U/ml in the RA, 30.4 U/ml in the SLE, 81.9 U/ml in the SS patients, and 46.6 U/ml in the HCs. The PAD4 levels were significantly higher in the RA than in the SLE patients or the HCs. Anti-PAD4 Abs were detected in 29.7 % of the patients with RA, but not in the patients with SLE or SS, nor in the HCs. In the RA patients, the PAD4 levels in the anti-PAD4 Ab-negative group were significantly higher than those in the anti-PAD4 Ab-positive group. Moreover, anti-CCG-2, CCG-7, CEP-1, and anti-CCP Ab levels were significantly higher in the anti-PAD4 Ab-positive group than in the anti-PAD4 Ab-negative group. In the RA patients, the PAD4 levels were not correlated with ACPAs. Neither PAD4 nor anti-PAD4 Abs were significantly correlated with the presence of SE alleles. The PAD4 levels were higher in RA than in SLE or HC. Anti-PAD4 Abs appeared specifically in patients with RA. Moreover, anti-PAD4 Abs were associated with ACPAs.
27385076 Effects of treatment with etanercept versus methotrexate on sleep quality, fatigue and sel 2016 Sep OBJECTIVES: To compare sleep quality, disease activity and patient-reported outcomes such as fatigue and immune parameters in patients with rheumatoid arthritis treated with etanercept (ETA) or methotrexate (MTX). METHODS: Of 36 patients (28-joint Disease Activity Score, DAS28CRP≥3.2) in this 16-week (w), open, prospective study, 19 (11 women) received MTX 12.5-17 mg/w, and 17 (14 women) received ETA 25 mg x 2/w, alone or in combination with MTX. Clinical (DAS28CRP, visual analogue scale), laboratory (C-reactive protein [CRP]), sleep (polysomnography), functional (Multidimensional Fatigue Inventory; Health Assessment Questionnaire-Disability Index (HAQ-DI); 36-item Short-Form Health Survey (SF-36), immunological (humoral/cellular) and neuroendocrine (hormonal) parameters were recorded at baseline (BL), w8 and w16. RESULTS: BL characteristics did not differ significantly between the ETA and MTX groups except disease duration: mean age (years): 48.6±8.8 vs. 49.4±16.6; mean disease duration (months): 19.6±46.3 vs. 81.2±79.2; and DAS28CRP: 4.4±0.9 vs. 4.4±1.7, respectively. DAS28CRP, SF-36, and HAQ-DI improved significantly in both groups from BL to w16 (p≤0.05). The DAS28CRP improvements at w16 (mean changes -1.8 in the ETA group, and -1.4 in MTX group), were not statistically significant from each other. The absolute values of sleep efficiency, total sleep time, and stage 2 sleep duration increased significantly in the ETA group, but no significant changes were reported in the MTX group. CONCLUSIONS: Both therapies improved disease activity, CRP, SF-36 and HAQ-DI, with faster, more pronounced changes in DAS28CRP in the ETA group, which alone had significantly improved sleep parameters.
25535886 Circadian rhythms of cellular immunity in rheumatoid arthritis: a hypothesis-generating st 2015 Jan OBJECTIVES: The circadian rhythm of clinical symptoms in rheumatoid arthritis (RA) has been primarily attributed to circadian variations in humoral factors and hormones. In this study, we investigated circadian rhythms of cellular immunity in RA (CiRA study). METHODS: Peripheral blood of female postmenopausal patients with active RA (DAS 28 ≥ 4.2) (n=5) and female postmenopausal non-RA controls (n=5) was collected every 2 hours for 24 hours and analysed by flow cytometry, cytokine multiplex suspension array and quantitative RT-PCR of clock gene expression in isolated CD14+ monocytes. Endogenous circadian rhythms of macrophages were investigated by BMAL1-luciferase bioluminescence. Significance of circadian rhythms was tested by Cosinor analysis. RESULTS: We found (i) circadian rhythms in the relative frequency of peripheral blood cell populations that were present in postmenopausal non-RA controls but absent in patients with active RA, (ii) circadian rhythms that were absent in non-RA controls but present in patients with RA and (iii) circadian rhythms that were present in both groups but with differences in peak phase or amplitude or amplitude/magnitude. The circadian rhythm in expression of the clock genes PER2 and PER3 in CD14+ monocytes was lost in patients with RA. The amplitude of BMAL1-luciferase bioluminescence tended to be lower in patients with RA than in non-RA controls. CONCLUSIONS: We conclude that (i) in RA some immune cell populations lose their normal circadian rhythms whereas others establish new 'inflammatory' circadian rhythms and (ii) these findings provide a good basis for further identifying pathophysiological aspects of RA chronobiology with potential therapeutic implications.
26613768 Comparison of lipid and lipid-associated cardiovascular risk marker changes after treatmen 2016 Oct OBJECTIVE: Compare changes in lipids and lipid-associated cardiovascular (CV) risk markers in patients with rheumatoid arthritis (RA) treated with tocilizumab or adalimumab. METHODS: Post-hoc analysis was performed in patients with RA who received tocilizumab intravenously every 4 weeks or adalimumab subcutaneously every 2 weeks for 24 weeks in the ADACTA trial. Lipid and lipid-associated CV risk biomarkers, including high-density lipoprotein-associated serum amyloid-A (HDL-SAA), secretory phospholipase A2 IIA (sPLA2 IIA) and lipoprotein(a) (Lp(a)), were measured at baseline and at week 8. RESULTS: The study included 162 patients treated with tocilizumab and 162 patients treated with adalimumab; HDL-SAA and sPLA2 IIA were measured in a subpopulation of 87 and 97 patients, respectively. Greater increases in mean low-density lipoprotein cholesterol (LDL-C) (0.46 mmol/L (95% CI 0.30 to 0.62)), high-density lipoprotein cholesterol (HDL-C) (0.07 mmol/L (0.001 to 0.14)), total cholesterol (TC) (0.67 mmol/L (0.47 to 0.86)), triglycerides (0.24 mmol/L (0.10 to 0.38)) and TC:HDL ratio (0.27 (0.12 to 0.42)) occurred with tocilizumab from baseline to 8 weeks. HDL-SAA, sPLA2 IIA and Lp(a) decreased more with tocilizumab than adalimumab. Median changes from baseline to week 8 were -3.2 and -1.1 mg/L (p=0.0077) for HDL-SAA and -4.1 and -1.3 ng/mL (p<0.0001) for sPLA2 IIA; difference in adjusted means was -7.12 mg/dL (p<0.0001) for Lp(a). Similar results were observed in efficacy responders and non-responders per American College of Rheumatology and European League against Rheumatism criteria. CONCLUSION: LDL-C and HDL-C increased more with tocilizumab than adalimumab. HDL-SAA, sPLA2 IIA and Lp(a) decreased more with tocilizumab. Lipid change effects of interleukin-6 and tumour necrosis factor (TNF) inhibition, manifest by their net impact on lipids and lipoproteins, are not synonymous; the clinical significance is unclear and requires further study. TRIAL REGISTRATION NUMBER: NCT01119859.; post-results.
26844569 The Link Between CD6 and Autoimmunity: Genetic and Cellular Associations. 2016 The cell surface glycoprotein CD6 is expressed on leukocytes and mediates T cell trafficking across endothelial cell barriers. There is evidence suggesting that CD6 is implicated in the pathogenesis of autoimmune diseases, including multiple sclerosis (MS) and rheumatoid arthritis (RA). CD166, the physiological ligand of CD6, is expressed on endothelial cells in the central nervous system and in the collagen tissue of joints as well as on the cell surface of synovial fibroblasts. Animal models and in vitro experiments have shown that CD166 facilitates leukocyte trafficking into the central nervous system and mediates interactions of synovial cells with T lymphocytes, thereby representing a possible common mechanism of pathogenesis in MS and RA. In recent years, genome-wide association studies (GWAS) have established a genetic link between CD6 and MS. The single nucleotide polymorphism (SNP) rs17824933 in the CD6 gene has been identified and validated as a genetic risk factor for the development of MS. The SNP is associated with altered CD4+ T cell functions and with the expression of alternative CD6 splice variants in T cells. Several other independent CD6 gene polymorphisms have been associated with disease susceptibility or with clinical features such as worse attack recovery in MS. In addition to the genetic associations found in MS, an allelic variant of the CD6 gene correlates with clinical response to tumor necrosis factor-α (TNF-α) inhibitors in patients with RA. Preliminary data indicate that anti-CD6 blockade may be a promising tool for the treatment of RA and psoriasis. Taken together, genetic associations and clinical observations provide new evidence for a role of CD6 in autoimmunity.
26073022 Menaquinone-7 as a novel pharmacological therapy in the treatment of rheumatoid arthritis: 2015 Aug 15 Menaquinones (MKs) have been reported to induce apoptosis in rheumatoid arthritis (RA) synovial cells. Recently, menaquinone-4 (MK-4) was proven as a new potential agent for the treatment of RA. However, menaquinone-7 (MK-7) has greater bioavailability and efficacy than MK-4 after oral administration. Yet, the therapeutic benefits of MK-7 in the management of patients with RA have never been addressed. This study was designed to clarify the therapeutic role of MK-7 added to normal therapeutic regimen of RA in patients with different stages of the disease with a clinical follow up through a randomized clinical trial. In a cross sectional study, 84 RA patients (24 male, 60 female) (average age=47.2 years) were enrolled in this study. The patients were divided into MK-7 treated group (n=42) and MK-7 naïve group (n=42). MK-7 capsules were administered in a dose of 100µg/day for three months in the first group without changing in other medications. The clinical and biochemical markers on RA patients treated with MK-7 and naïve group were assessed. In MK-7 treated group, serum concentrations of MK-7 were monitored before and after three months of MK-7 administration. In the cross sectional study, a significant decrease in MK-7 treated group for the levels of undercarboxylated osteocalcin (ucOC), erythrocyte sedimentation rate (ESR), disease activity score assessing 28 joints with ESR (DAS28-ESR), C-reactive protein (CRP) and matrix metalloproteinase (MMP-3) was found. In MK-7 treated group, a marked decrease in RA clinical and biochemical markers for moderate and good response compared to non-responders was observed in ucOC, ESR and DAS28-ESR. A marked increase in the levels of MK-7 for the moderate and good responders compared to non-responders was observed. The results suggest that MK-7 improves disease activity in RA patients. Therefore, MK-7 represents a new promising agent for RA in combination therapy with other disease modifying antirheumatic drugs.
24106048 Anti-citrullinated protein antibodies acquire a pro-inflammatory Fc glycosylation phenotyp 2015 Jan OBJECTIVE: To determine whether anticitrullinated protein antibodies (ACPA) exhibit specific changes in Fc glycosylation prior to the onset of arthritis. METHODS: Serum samples of patients with ACPA-positive arthralgia (n=183) were collected at baseline and at various time points of follow-up. 105 patients developed arthritis after a median of 12 months (IQR 6-24) and were classified as having either rheumatoid arthritis (RA, n=48) or undifferentiated arthritis (UA, n=57) based on the 1987 American College of Rheumatology (ACR) criteria. ACPA and total serum IgG were isolated by affinity purification and cleaved by trypsin. ACPA-IgG1 Fc-glycopeptides were subsequently analysed by nano-liquid chromatography mass spectrometry and compared to those of total IgG1. RESULTS: At baseline, ACPA-IgG1 and total IgG1 from arthralgia patients displayed similar Fc glycosylation patterns. By contrast, at the onset of arthritis, ACPA exhibited a decrease in galactose residues in RA patients, but not in UA patients. This decrease occurred around 3 months prior to diagnosis and was paralleled by an increase in systemic inflammation (erythrocyte sedimentation rate). Galactosylation of total IgG1 was also decreased in RA, but this did not precede the onset of arthritis. Interestingly, we additionally noted a higher degree of ACPA-IgG1 Fc core fucosylation at baseline as compared with total IgG1, which further increased prior to diagnosis. CONCLUSIONS: ACPA display significant changes in Fc galactosylation and fucosylation prior to the onset of RA. These changes towards a more pro-inflammatory phenotype could be involved in driving the disease process.
26467222 Continuously elevated serum matrix metalloproteinase-3 for 3 ~ 6 months predict one-year r 2015 Oct 14 INTRODUCTION: Core disease activity indicators of rheumatoid arthritis (RA) have been found to be limited in predicting joint destruction progression. Matrix metalloproteinase (MMP) 3 plays an essential role in joint destruction and was found elevated in some remission patients. We aimed to monitor dynamic core disease activity indicators and serum MMP-3 for one year and evaluate their value for predicting radiographic progression. METHODS: Patients with active RA (Simplified disease activity index > 3.3) were treated according to the treat-to-target strategy. Serum MMP-3 was detected by enzyme-linked immunosorbent assay and clinical data were collected simultaneously at 0, 1st, 3rd, 6th and 12th month. X-ray assessment of hand/wrist was repeated at baseline and the 12th month and a change of total Sharp score > 0.5 units was defined as radiographic progression. RESULTS: Fifty-six patients completed one year follow-up and 29 % showed radiographic progression. Although not significantly different at baseline, serum MMP-3 and all core disease activity indicators, except for erythrocyte sedimentation rate, at the 12th month were significantly higher in the progressive group than in the non-progressive group. Among sixteen progressive patients, 69 % achieved the therapeutic target and 56 % had continuous elevated serum MMP-3, 38 % had continuous elevated serum MMP-3 and normal C-reactive protein (CRP) at the 6th month. Log-rank tests and repeated measures analysis revealed a significant difference in dynamic serum MMP-3 between progressive and non-progressive patients. Receiver operating characteristic curve and univariate logistic regression analysis showed that elevated serum MMP-3 at 0, 1st, 3rd and 6th months, compared with CRP at the 1st month, were significant predictors for one-year radiographic progression (MMP-3 odds ratio (OR):10.500 ~ 27.000, all P < 0.05; CRP: OR = 7.400, P = 0.011). CONCLUSIONS: Our data showed that continuously elevated serum MMP-3 for 3 ~ 6 months predicted one-year radiographic progression which implied that monitoring of dynamic serum MMP-3 combined with core disease activity indicators may be more helpful for predicting radiographic progression and treatment decision in RA.
27165496 Biological Therapy-Induced Systemic Vasculitis. 2016 Jul The use of biologics has been associated with the paradoxical development of biologics-induced autoimmune diseases. The purpose of this review was to describe the key immunopathogenic mechanisms involved in the development of these conditions, and to discuss the clinical and laboratory characteristics usually described in the medical literature, reviewing case reports as well as records on national biologic therapies (BIOGEAS, RABBIT, BSRBR-RA, BIOBADAVEN). More than 200 cases have so far been reported, all of them diagnosed on the basis of the histopathology or meeting the ACR/Chapel Hill criteria. Over 75 % of the cases were females with a mean age of 48 ± 5 years. More than 50 % had rheumatoid arthritis. Most of the biologics-associated vasculitis developed in 90 ± 31 days. Complete resolution in almost 75 % of the cases was observed upon treatment discontinuation; however, steroid therapy was indicated for all patients and one death was recorded. The use of cyclophosphamide, rituximab or plasma exchange was reserved for the most severe cases.