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ID PMID Title PublicationDate abstract
25940140 Weight Loss, the Obesity Paradox, and the Risk of Death in Rheumatoid Arthritis. 2015 Jul OBJECTIVE: In contrast to what is observed in the general population, a low body mass index (BMI) has been associated with accelerated mortality in patients with rheumatoid arthritis (RA). The aim of this study was to assess whether weight loss might explain these seemingly paradoxical observations. METHODS: Our study included patients identified from the Veterans Affairs (VA) RA Registry. Dates of death were abstracted from VA electronic medical records. The BMI at each study visit and the change from the previous visit were determined. The maximum BMI of each patient was also obtained from medical records. The annualized rate of BMI loss was determined from the slope of change (per year) in BMI over visits within the preceding 13 months. Cox multivariable proportional hazards models were used to assess associations between BMI measures and mortality. RESULTS: In a sample of 1,674 patients, 312 deaths occurred over 9,183 person-years. A loss in BMI of ≥1 kg/m(2) was associated with a greater risk of death, after adjustment for demographics, comorbidities, BMI, smoking, and RA therapies (hazard ratio [HR] 1.99, 95% confidence interval [95% CI] 1.53-2.59, P < 0.001). This association remained significant in a subsample analysis adjusting for C-reactive protein and physical function (HR 1.81, 95% CI 1.36-2.41, P < 0.001). Weight loss at an annualized rate of ≥3 kg/m(2) was associated with the greatest risk of death (HR 2.49, 95% CI 1.73-3.57, P < 0.001). Low BMI (<20 kg/m(2) ) in patients with a history of obesity (>30 kg/m(2) ) was associated with the greatest risk (HR 8.52, 95% CI 4.10-17.71, P < 0.001). CONCLUSION: Weight loss is a strong predictor of death in patients with RA. These observations may explain the observed obesity paradox and do not support a biologically protective role of obesity.
25793532 Defining immunological impact and therapeutic benefit of mild heating in a murine model of 2015 Traditional treatments, including a variety of thermal therapies have been known since ancient times to provide relief from rheumatoid arthritis (RA) symptoms. However, a general absence of information on how heating affects molecular or immunological targets relevant to RA has limited heat treatment (HT) to the category of treatments known as "alternative therapies". In this study, we evaluated the effectiveness of mild HT in a collagen-induced arthritis (CIA) model which has been used in many previous studies to evaluate newer pharmacological approaches for the treatment of RA, and tested whether inflammatory immune activity was altered. We also compared the effect of HT to methotrexate, a well characterized pharmacological treatment for RA. CIA mice were treated with either a single HT for several hours or daily 30 minute HT. Disease progression and macrophage infiltration were evaluated. We found that both HT regimens significantly reduced arthritis disease severity and macrophage infiltration into inflamed joints. Surprisingly, HT was as efficient as methotrexate in controlling disease progression. At the molecular level, HT suppressed TNF-α while increasing production of IL-10. We also observed an induction of HSP70 and a reduction in both NF-κB and HIF-1α in inflamed tissues. Additionally, using activated macrophages in vitro, we found that HT reduced production of pro-inflammatory cytokines, an effect which is correlated to induction of HSF-1 and HSP70 and inhibition of NF-κB and STAT activation. Our findings demonstrate a significant therapeutic benefit of HT in controlling arthritis progression in a clinically relevant mouse model, with an efficacy similar to methotrexate. Mechanistically, HT targets highly relevant anti-inflammatory pathways which strongly support its increased study for use in clinical trials for RA.
25163737 Predictors of response to TNF antagonists. 2015 Rheumatoid arthritis (RA) is a chronic inflammatory disease that involves synovial tissue and leads to joint destruction. There are currently 5 tumor necrosis factor (TNF) antagonists licensed for the treatment of RA. This review summarizes the predictors of response to TNF antagonists in RA. Demographic variables were found to predict response, although not consistently. The variables associated with poor clinical response were presence of radiographic joint erosions at baseline, poor functional capacity at baseline, presence of human antibodies against TNF chimeric antibodies, and increase in anti-DNA and antinuclear antibodies. In selected populations, polymorphisms of TNF, TNF receptor, and Fc γ receptor were related to clinical response. Expression of TNF and other inflammatory cytokines in synovial tissue was explored. The heterogeneity of study populations limits the generalizability of the results in most studies.
27987493 [Significance of antibodies to the citrullinated glucose-6-phosphate isomerase peptides in 2016 Dec 18 OBJECTIVE: To detect the anti-citrullinated glucose-6-phosphate isomerase (GPI) 70-88 peptide antibody (anti-C-GPI(70-88) antibody), anti-citrullinated GPI 435-453 peptide antibody (anti-C-GPI(435-453) antibody), anti-GPI 70-88 peptide antibody (anti-GPI(70-88) antibody) and anti-GPI 435-453 peptide antibody(anti-GPI(435-453) antibody) in the serum of rheumatoid arthritis (RA) patients, and examine the diagnostic values of the anti-C-GPI peptide antibodies in RA. METHODS: The anti-C-GPI(70-88) antibody, anti-C-GPI(435-453) antibody, anti-GPI(70-88) antibody and anti-GPI(435-453) antibody were detected by enzyme-linked immunosorbent assay (ELISA) in 191 RA patients, 129 other rheumatic diseases and 74 healthy controls. The clinical and laboratory data of the patients with RA were collected, and the values of anti-C-GPI peptide antibodies in the diagnosis of RA and the relationships of anti-C-GPI peptide antibodies with the clinical and laboratory parameters analyzed. RESULTS: (1) The mean titers of the anti-C-GPI(70-88) antibody and the anti-C-GPI(435-453) antibody in the RA patients (respectively, 68.71 ± 4.20 and 51.78 ± 3.13) were significantly higher than those with other rheumatic diseases and healthy individuals (P <0.05). However, the mean titers of the anti-GPI(70-88) antibody and anti-GPI(435-453) antibody in the RA patients were similar to those with other rheumatic diseases and healthy individuals. (2) The diagnostic sensitivity and specificity of the anti-C-GPI(70-88) antibody for RA were 41.88% and 84.50% respectively; and the diagnostic sensitivity and specificity of the anti-C-GPI(435-453) antibody for RA were 46.05% and 86.05% respectively. The sensitivity of combined detection of the two anti-C-GPI peptide antibodies was 50.79%, and the specificity was 81.40%. (3) The positive rates of the anti-C-GPI(70-88) antibody and the anti-C-GPI(435-453) antibody were 35% and 45% respectively in those patients with negative anti-cyclic citrullinated peptide antibody, anti-keratin antibody, and rheumatoid factor. (4) There was no significant difference in clinical and laboratory indicators between the anti-C-GPI(70-88) antibody or anti-C-GPI(435-453) antibody positive group and negative group. CONCLUSION: The anti-C-GPI(70-88) antibody and anti-C-GPI(435-453) antibody can be detected in the serum of RA patients, and C-GPI may be involved in the pathogenesis of RA. There is a certain diagnostic significance for the sera-negative RA.
27237922 Dermoscopy of nail fold and elbow in the differential diagnosis of early psoriatic arthrit 2016 Oct Differentiation between psoriatic arthritis (PsA) sine psoriasis and rheumatoid arthritis (RA) may be a challenge, especially in the early stages, hence the need for new instrumental markers to assist their diagnosis. In this study, we investigated possible dermoscopic differences in vascular appearance of nail fold and elbow (a classic site of repeated trauma) in these two conditions. Fifteen patients with PsA sine psoriasis, 12 patients with RA and 12 controls were included in the study. Regarding the nail fold vascular appearance in PsA sine psoriasis and RA cohorts, the presence of diffuse reddish background with or without sparse dotted vessels was significant in the former, whereas the evidence of parallel dotted/short linear vessels ("fish school-like" pattern) or irregular/ramified, blurry, purple vessels were significant in the latter; none of these patterns were detected in the control group. Regarding the elbow, the pattern significantly associated with PsA sine psoriasis consisted of diffusely distributed, red, dotted vessels. On the other hand, RA patients and controls displayed similar dermoscopic findings, with three possible vascular patterns being observed: (i) irregular, blurry, purple vessels; (ii) avascular appearance; and (iii) sparse, dotted, purple vessels. In conclusion, dermoscopy may be a useful supportive tool for differentiating early PsA sine psoriasis from RA.
27312970 Interleukin 12B gene polymorphisms and susceptibility to rheumatoid arthritis: a data synt 2017 Feb The aim of this study was to investigate the association of two common interleukin 12B (IL-12B) polymorphisms (rs3212227 and rs6887695) with rheumatoid arthritis (RA) susceptibility through meta-analyses. A systematic literature search of PubMed, Web of Science, Cochrane Library, and Embase databases was conducted on articles published before 28 February 2016. Then odds ratio (OR) with 95 % confidence interval (CI) was used to quantify the strength of association for homozygote, heterozygote, dominant, and recessive genetic models. Nine articles with a total of 17 case-control studies (12 for IL-12B rs3212227 polymorphism and 5 for IL-12B rs6887695 polymorphism) met our inclusion criteria. The pooled results demonstrated that IL-12B rs3212227 (homozygote model: OR = 0.96, 95 % CI = 0.81-1.15; heterozygote model: OR = 1.07, 95 % CI = 0.93-1.23; dominant model: OR = 1.05, 95 % CI = 0.91-1.20; recessive model: OR = 0.93, 95 % CI = 0.79-1.10) and rs6887695 (homozygote model: OR = 1.01, 95 % CI = 0.84-1.21; heterozygote model: OR = 1.14, 95 % CI = 0.86-1.51; dominant model: OR = 1.14, 95 % CI = 0.87-1.48; recessive model: OR = 1.01, 95 % CI = 0.85-1.21) polymorphisms may not be associated with RA risk. Our meta-analyses demonstrated that IL-12B rs3212227 and rs6887695 polymorphisms do not confer susceptibility to RA.
27355283 Complications of Primary Total Knee Arthroplasty Among Patients With Rheumatoid Arthritis, 2016 Aug BACKGROUND: Although several studies have reported outcomes of primary total knee arthroplasty (TKA) in patients with rheumatoid arthritis, very little has been reported on the outcomes of this procedure in patients with other inflammatory arthritides. METHODS: This study used a national database to evaluate 90-day postoperative complication rates, readmission rates, and revision rates after TKA in patients with inflammatory arthritis. Patients with rheumatoid arthritis (n = 153,531), psoriatic arthritis (n = 7,918), and ankylosing spondylitis (n = 4,575) were compared with patients with osteoarthritis (n = 1,751,938) who underwent TKA from 2005 to 2012. RESULTS: The rates of systemic complications, infection, revision, and 90-day readmission after TKA in patients with different types of inflammatory arthritis were significantly higher than those in control patients with osteoarthritis (P < 0.0001). No differences were found in the rates of systemic or local complications, revision, or readmission among the types of inflammatory arthritis. CONCLUSION: Inflammatory arthritis is associated with increased rates of perioperative complications, revision, and 90-day readmission after primary TKA. LEVEL OF EVIDENCE: Level III.
26860413 Rheumatoid factor isotypes in relation to antibodies against citrullinated peptides and ca 2016 Feb 9 BACKGROUND: The presence of rheumatoid factor (RF), anti-carbamylated protein antibodies (anti-CarP) and antibodies against citrullinated protein and peptides (ACPA) precedes the onset of symptoms of rheumatoid arthritis (RA) by several years. Relationships between the development of these antibodies are not obvious. METHODS: Three isotypes [immunoglobulin A (IgA), IgG and IgM) of RF were analysed in 321 pre-symptomatic individuals who provided 598 samples collected a median of 6.2 (interquartile range 7.2) years before the onset of symptoms, and in 492 population control subjects. All samples were donated to the Biobank of Northern Sweden. RF isotypes were analysed using the EliA system (Phadia GmbH, Freiburg, Germany) with 96 % specificity according to receiver operating characteristic curves. Ten ACPA specificities were analysed using the ImmunoCAP ISAC system, and anti-CCP2 and anti-CarP antibodies were evaluated using enzyme-linked immunosorbent assays. RESULTS: The frequencies of RF isotypes in pre-symptomatic individuals were significantly increased compared with control subjects (p < 0.0001). In samples collected ≥15 years before the onset of symptoms, the IgA-RF isotype was significantly more prevalent than the most frequent ACPAs. Combinations of IgM- and IgA-RF isotypes with ACPA specificities [α-enolase (CEP-1/Eno5-21)], fibrinogen (Fib)β36-52, Fibα580-600, filaggrin (CCP-1/Fil307-324) and anti-CCP2 antibodies were associated with a significantly shorter time to onset of symptoms (p < 0.001-0.05). Using conditional inference tree analysis, anti-CCP2 in combination with anti-filaggrin antibodies gave the highest probability, 97.5 %, for disease development. CONCLUSIONS: RF isotypes predicted the development of RA, particularly in combination with ACPA, anti-CCP2 or anti-CarP antibodies. The highest probability for disease development was the presence of anti-CCP2 and anti-filaggrin antibodies.
26271387 Paradoxical Expansion of Th1 and Th17 Lymphocytes in Rheumatoid Arthritis Following Inflix 2015 Aug PURPOSE: The immunogenicity of anti-TNF-α drugs may affect their safety and efficacy. Infliximab (IFX), a chimeric monoclonal antibody, induces antibody formation in up to 60% of cases. Some studies have suggested the involvement of a Th1 response to TNFα blockers following immunization, but the triggering of Th17 responses has never been reported. The aim of this study is to investigate whether the immunogenicity of IFX affects the Th1, Th17 and Treg compartments in rheumatoid arthritis (RA) patients failing IFX therapy, and verify whether this may be responsible for treatment failure. METHODS: The study involved 55 patients with RA (15 treatment-naïve patients; 20 IFX responders; 20 IFX non-responders) and 10 healthy controls. PBMCs were cultured in the presence/absence of IFX, and the variations in the percentage of Th1, Th17 and Treg lymphocytes following IFX treatment were analysed. RESULTS: IFX-specific Th1 and Th17 responses and an increase in IL-21 production were observed in patients failing IFX (p < 0.01, p < 0.05, and p < 0.01 respectively). In contrast, IFX incubation reduced significantly Th1 and Th17 responses and IL-21 production (p < 0.05) in successfully-treated subjects, but did not affect these responses in healthy controls or treatment-naïve patients. CONCLUSIONS: RA patients may have impaired peripheral tolerance, which could favour the development of an aberrant immunological response to biological drugs. The loss of therapeutic effectiveness of IFX and the onset of adverse events may be due to a paradoxical activation of Th17 or Th1 lymphocytes following sensitisation, thus worsening the patients' inflammatory status.
24737786 Cost-effectiveness of infliximab versus conventional combination treatment in methotrexate 2015 Jun OBJECTIVE: To estimate the incremental cost-effectiveness of infliximab versus conventional combination treatment over 21 months in patients with methotrexate-refractory early rheumatoid arthritis. METHODS: In this multicentre, two-arm, parallel, randomised, active-controlled, open-label trial, rheumatoid arthritis patients with <1 year symptom duration were recruited from 15 rheumatology clinics in Sweden between October 2002 and December 2005. After 3-4 months of methotrexate monotherapy, patients not achieving low disease activity were randomised to addition of infliximab or sulfasalazine+hydroxychloroquine (conventional treatment group). Costs of drugs, healthcare use, and productivity losses were retrieved from nationwide registers, while EuroQol 5-Dimensions utility was collected quarterly. RESULTS: Of 487 patients initially enrolled, 128 and 130 were randomised to infliximab and conventional treatment, respectively. The infliximab group accumulated higher drug and healthcare costs (€27,487 vs €10,364; adjusted mean difference €16,956 (95% CI 14,647 to 19,162)), while productivity losses did not differ (€33,804 vs €29,220; €3961 (95% CI -3986 to 11,850)), resulting in higher societal cost compared to the conventional group (€61,291 vs €39,584; €20,916 (95% CI 12,800 to 28,660)). Mean accumulated quality-adjusted life-years (QALYs) did not differ (1.10 vs 1.12; adjusted mean difference favouring infliximab treatment 0.01 (95% CI -0.07 to 0.08)). The incremental cost-effectiveness ratios for the infliximab versus conventional treatment strategy were €2,404,197/QALY from the societal perspective and €1,948,919/QALY from the healthcare perspective. CONCLUSIONS: In early, methotrexate-refractory rheumatoid arthritis, a treatment strategy commencing with addition of infliximab, as compared to sulfasalazine+hydroxychloroquine, was not cost-effective over 21 months at willingness to pay levels generally considered acceptable. TRIAL REGISTRATION NUMBER: NCT00764725.
26201085 Remodeling of plasma lipoproteins in patients with rheumatoid arthritis: Interleukin-6 rec 2016 Feb PURPOSE: Rheumatoid arthritis (RA) is associated with increased cardiovascular risk, mediated in part by elevated circulating interleukin-6 levels and proinflammatory changes in plasma lipoproteins. We hypothesized that RA patients acquire inflammation-induced modifications to the protein cargo of circulating lipoproteins that may be reversed by tocilizumab, an interleukin-6 receptor-alpha inhibitor. EXPERIMENTAL DESIGN: Size-exclusion chromatography and reverse-phase protein arrays using 29 antibodies against 26 proteins were applied at baseline and after tocilizumab treatment to analyze the distributions of apolipoproteins, enzymes, lipid transfer proteins, and other associated proteins in plasma lipoprotein fractions from 20 women with RA. RESULTS: A 30% reduction in high-density lipoprotein (HDL)-associated serum amyloid A4 and complement C4 occurred with tocilizumab. Levels of C-reactive protein, associated or comigrating with HDL and low-density lipoprotein (LDL) peaks, were reduced on treatment by approximately 80% and 24%, respectively. Reductions in lipoprotein-associated phospholipase A2, lipoprotein (a), and cholesteryl ester transfer protein in the LDL fraction suggest reductions in LDL-associated proatherogenic factors. Elevations in very low-density lipoprotein (VLDL) enriched with apolipoprotein E were equally observed. CONCLUSIONS AND CLINICAL RELEVANCE: Tocilizumab treatment led to reductions in proinflammatory components and proatherogenic proteins associated with HDL. Whether changes in the proteome of VLDL, LDL, and HDL induced by anti-inflammatory tocilizumab treatment in RA patients modify cardiovascular disease risk requires further investigation.
26879423 Exploration of the serum metabolite signature in patients with rheumatoid arthritis using 2016 Aug 5 Rheumatoid arthritis (RA) is a systemic autoimmune disease with complicated pathogeny. There could be obvious alterations of metabolism in the patients with RA and the discovery of metabolic signature may be helpful for the accurate diagnosis of RA. In order to explore the distinctive metabolic patterns in RA patients, a gas chromatography-mass spectrometry (GC-MS) method was employed. Serum samples from 33 RA patients and 32 healthy controls were collected and analyzed. Acquired metabolic data were assessed by the principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA), and the data analysis results showed RA patients and healthy controls have very different metabolic profiles. Variable importance for project values (VIP) and Student's t-test were combined to screen the significant metabolic changes caused by RA. Serums from RA patients were featured by decreased levels of amino acids and glucose, increased levels of fatty acids and cholesterol, which were primarily associated with glycolytic pathway, fatty acid and amino acid metabolism, and other related pathways including TCA cycle and the urea cycle. These preliminary results suggest that GC-MS based metabolic profiling study appears to be a useful tool in the exploration of the metabolic signature of RA, and the revealed disease-associated metabolic perturbations could help to elucidate the pathogenesis of RA and provide a probable aid for the accurate diagnosis of RA.
25745669 Intraductal papillary mucinous neoplasia--a challenging diagnosis in a patient with parane 2015 Mar Intraductal papillary mucinous neoplasias (IPMNs) of the pancreas are potentially malignant tumors, and associated also with extrapancreatic carcinomas. We present the case of a 80 year old man with IPMN and late onset of rheumatoid arthritis. The particularity of this case is the discordance between the clinical picture and the imaging worrisome features, together with the surgery-requiring mixed-type of IPMN, despite the late possible paraneoplastic onset of rheumatoid arthritis.
25766462 Neuromyelitis optica with cutaneous findings: case report and review of the literature. 2015 Neuromyelitis optica (NMO) is an autoimmune, relapsing central nervous system demyelinating disease. There is a known association between NMO and autoimmune disease. However, cutaneous findings in these cases and in the setting of isolated NMO have rarely been described. We report the case of a 60-year-old Chinese female who presented with nonspecific cutaneous findings and acute onset paraplegia and was subsequently found to be seropositive for aquaporin-4 (NMO IgG) antibodies, consistent with a diagnosis of NMO spectrum disorder. Serologic testing prompted by history and cutaneous stigmata revealed additional humoral derangements, together suggestive of an overlap syndrome with features of amyopathic dermatomyositis, rheumatoid arthritis and lupus erythematosus. We review the existing literature on the cutaneous manifestations of this entity. Awareness of the cutaneous signs and heralding symptoms of this devastating neurologic syndrome by dermatologists will ensure prompt diagnosis and initiation of treatment that can minimize neurologic sequelae.
26764260 Disease activity-guided dose optimisation of adalimumab and etanercept is a cost-effective 2016 Nov BACKGROUND: A disease activity-guided dose optimisation strategy of adalimumab or etanercept (TNFi (tumour necrosis factor inhibitors)) has shown to be non-inferior in maintaining disease control in patients with rheumatoid arthritis (RA) compared with usual care. However, the cost-effectiveness of this strategy is still unknown. METHOD: This is a preplanned cost-effectiveness analysis of the Dose REduction Strategy of Subcutaneous TNF inhibitors (DRESS) study, a randomised controlled, open-label, non-inferiority trial performed in two Dutch rheumatology outpatient clinics. Patients with low disease activity using TNF inhibitors were included. Total healthcare costs were measured and quality adjusted life years (QALY) were based on EQ5D utility scores. Decremental cost-effectiveness analyses were performed using bootstrap analyses; incremental net monetary benefit (iNMB) was used to express cost-effectiveness. RESULTS: 180 patients were included, and 121 were allocated to the dose optimisation strategy and 59 to control. The dose optimisation strategy resulted in a mean cost saving of -€12 280 (95 percentile -€10 502; -€14 104) per patient per 18 months. There is an 84% chance that the dose optimisation strategy results in a QALY loss with a mean QALY loss of -0.02 (-0.07 to 0.02). The decremental cost-effectiveness ratio (DCER) was €390 493 (€5 085 184; dominant) of savings per QALY lost. The mean iNMB was €10 467 (€6553-€14 037). Sensitivity analyses using 30% and 50% lower prices for TNFi remained cost-effective. CONCLUSIONS: Disease activity-guided dose optimisation of TNFi results in considerable cost savings while no relevant loss of quality of life was observed. When the minimal QALY loss is compensated with the upper limit of what society is willing to pay or accept in the Netherlands, the net savings are still high. TRIAL REGISTRATION NUMBER: NTR3216; Post-results.
25967237 Aberrant Activation of TGF-β in Subchondral Bone at the Onset of Rheumatoid Arthritis Joi 2015 Nov Rheumatoid arthritis (RA) is an autoimmune disease that often leads to joint destruction. A myriad of drugs targeting the immune abnormalities and downstream inflammatory cascades have been developed, but the joint destruction is not effectively halted. Here we report that aberrant activation of TGF-β in the subchondral bone marrow by immune response increases osteoprogenitors and uncoupled bone resorption and formation in RA mouse/rat models. Importantly, either systemic or local blockade of TGF-β activity in the subchondral bone attenuated articular cartilage degeneration in RA. Moreover, conditional deletion of TGF-β receptor II (Tgfbr2) in nestin-positive cells also effectively halted progression of RA joint destruction. Our data demonstrate that aberrant activation of TGF-β in the subchondral bone is involved at the onset of RA joint cartilage degeneration. Thus, modulation of subchondral bone TGF-β activity could be a potential therapy for RA joint destruction.
27658417 Optimizing therapy in inflammatory arthritis: prediction of relapse after tapering or stop 2016 Dec This study aims to assess clinical, lab/immunological or imaging (joint ultrasonography) markers able to predict disease relapse in RA patients in sustained remission when tapering or stopping their treatment. One hundred fifty-seven RA patients in clinical remission (DAS-28 <2.6 for >6 months), receiving treatment with sDMARDs and bDMARD therapy, were randomly allocated into any of five groups: Group 1: continue full dose DMARDs and taper biologic therapy by 50 % (31 patients); Group 2: taper both DMARDs and biologic therapy dose by 50 % (32 patients); Group 3: taper DMARDs by 50 % and stop biologic therapy (31 patients); Group 4: stop both DMARDs and biologic therapy (31 patients); Group 5: continue medications without change (31 patients). Forty joints were assessed ultrasonographically (DAS-28 joints + ankles + metatarsophalangeal joints) and prospectively monitored for 12 months. The primary endpoint was sustained remission for 12 months. Patients were considered as having a relapse when the DAS-28 score was >3.2 and anti-rheumatic treatment was escalated. The frequency of relapse was 41.9 % in Group 1, 59.3 % in Group 2, 67.7 % in Group 3, 77.4 % in Group 4 and 6.5 % in Group 5. Relapse rates were significantly higher in patients whose ultrasound scores raised within 3 months of stopping their medications (P < 0.001 for both GS and PD scores). Cox regression identified ACPA positivity (at baseline) and progression of functional disability (at 2 months) as predictors for relapse. Tapering therapy is feasible in RA patients. Tailored dynamic approach is advised. Joint ultrasonographic assessment, ACPA positivity and worsening functional disability predicted relapse within a short term after discontinuation of the treatment. RA patients whose DAS-28 score was <2 were more likely to remain in remission.
27626941 A Cytokine Signalling Network for the Regulation of Inducible Nitric Oxide Synthase Expres 2016 In rheumatoid arthritis (RA), nitric oxide (NO) is implicated in inflammation, angiogenesis and tissue destruction. The enzyme inducible nitric oxide synthase (iNOS) is responsible for the localised over-production of NO in the synovial joints affected by RA. The pro- and anti-inflammatory cytokines stimulate the synovial macrophages and the fibroblast-like synoviocytes to express iNOS. Therefore, the cytokine signalling network underlying the regulation of iNOS is essential to understand the pathophysiology of the disease. By using information from the literature, we have constructed, for the first time, the cytokine signalling network involved in the regulation of iNOS expression. Using the differential expression patterns obtained by re-analysing the microarray data on the RA synovium and the synovial macrophages available in the Gene Expression Omnibus (GEO) database, we aimed to establish the role played by the network genes towards iNOS regulation in the RA synovium. Our analysis reveals that the network genes belonging to interferon (IFN) and interleukin-10 (IL-10) pathways are always up-regulated in the RA synovium whereas the genes which are part of the anti-inflammatory transforming growth factor-beta (TGF-β) signalling pathway are mostly down-regulated. We observed a consistent up-regulation of the transcription factor signal transducers and activators of transcription 1 (STAT1) in the RA synovium and the macrophages. Interestingly, we found a consistent up-regulation of the iNOS interacting protein ras-related C3 botulinum toxin substrate 2 (RAC2) in the RA synovium as well as the macrophages. Importantly, we have constructed a model to explain the impact of IFN and IL-10 pathways on Rac2-iNOS interaction leading to over-production of NO and thereby causing chronic inflammation in the RA synovium. The interplay between STAT1 and RAC2 in the regulation of NO could have implications for the identification of therapeutic targets for RA.
25960619 Percentages of CD4+CD161+ and CD4-CD8-CD161+ T cells in the synovial fluid are correlated 2015 OBJECTIVE: CD161 has been identified as a marker of human IL-17-producing T cells that are implicated in the pathogenesis of rheumatoid arthritis (RA). This study aimed to investigate the potential link between the percentage of CD161+ T cells and disease activity in RA patients. METHODS: Peripheral blood (PB) from 54 RA patients and 21 healthy controls was evaluated. Paired synovial fluid (SF) (n = 17) was analyzed. CD161 expression levels on CD4+, CD8+, and CD4-CD8- T cells were assessed by flow cytometry. RESULTS: The percentage of CD4+CD161+ T cells in RA SF was higher than RA PB, and it was positively correlated with DAS28, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP). CD4-CD8-CD161+ T cell percentage was decreased in RA PB and was further reduced in RA SF, and its level in SF was inversely correlated with DAS28, ESR, and CRP. However, CD8+CD161+ T cell percentage was neither changed in RA PB and SF nor correlated with disease activity indices. CONCLUSION: An increased CD4+CD161+ T cell percentage and a decreased CD4-CD8-CD161+ T cell percentage are present in RA SF and are associated with disease activity, and the accumulation of CD4+CD161+ T cells in SF may contribute to the local inflammation of RA.
28471579 Balneotherapy and Rheumatoid Arthritis: A Randomized Control Trial. 2016 Aug BACKGROUND: The effects of balneotherapy on rheumatoid arthritis (RA) are still controversial partly due to poor methodology used in randomized controlled trials, as reported in the international medical literature. OBJECTIVES: To determine whether spa therapy plus pharmacological treatment offers any benefit in the management of RA as compared to pharmacological treatment alone. METHODS: We conducted a prospective, controlled, unblinded randomly assigned study of patients with RA according to American College of Rheumatology criteria. Following the 2007 recommendations of AFRETH, the method designed for this study was "immediate treatment versus delayed treatment." All patients were followed at the Centro Hospitalar do Porto and each physician observed the same patients throughout the study. Patients continued with their usual medications and maintained their daily life activities at home, at leisure and/or in the workplace. The spa therapy group received spa treatments for 21 days at S. Jorge Spa-Santa Maria da Feira. The main outcome measure was the HAQ-DI; the moderated regression analysis, together with the Johnson-Neyman technique, was used for statistical analysis. RESULTS: HAQ-DI at the end of treatment (21 days) and at the 3 month follow-up was improved in the spa group (odds ratio 0.37, confidence interval 0.09-0.64, P = 0.01 at 21 days, and 0.44, 0.15-0.72, P = 0.004 at 3 months). CONCLUSIONS: In individuals in whom pain (physical and psychological) predominates, any complementary gain in function is beneficial. The main goal is to enhance quality of life.