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ID PMID Title PublicationDate abstract
24306025 Salmonella septic arthritis in a patient receiving etanercept: case report and review of t 2013 Dec Antitumor necrosis factor alpha agents are known to increase the risk for severe and atypical infections. Numerous atypical organisms have been reported previously, however, there is a paucity of reports of Salmonella as a complication of these therapies. We report a case of a 69-year-old female who developed Salmonella septic arthritis of the pubic symphysis while taking etanercept that resolved with cessation of etanercept and antibiotic treatment and we review the literature regarding this complication. Awareness of susceptibility to Gram-negative intracellular organisms and reactivation of dormant infections due to the mechanism of action of antitumor necrosis factor alpha medications is vital.
24442879 Significant associations of antidrug antibody levels with serum drug trough levels and the 2015 Mar OBJECTIVE: To evaluate the associations between (1) antidrug antibody (ADAb) and therapeutic response, (2) ADAb and serum drug trough levels and (3) serum drug levels and therapeutic responses in rheumatoid arthritis (RA) patients receiving adalimumab or etanercept. Secondarily, we aim (1) to evaluate the concordance between radioimmunoassay and bridging ELISA for ADAb assessment and to evaluate the correlation between two different ELISA methods for detecting drug levels, and (2) to determine the optimal cut-off drug levels for good European League Against Rheumatism (EULAR) response. METHODS: ADAb levels were determined by bridging ELISA and radioimmunoassay, and drug levels evaluated using sandwich ELISA among 36 adalimumab-treated patients and 34 etanercept-treated patients at the 6th and 12th month. The optimal cut-off drug levels for EULAR responses were determined by receiver-operating characteristic curve analysis. RESULTS: ADAb was detected in 10 (27.8%) and 13 (36.1%) of adalimumab-treated patients after 12-month therapy using bridging ELISA and radioimmunoassay respectively, but not detected in any of etanercept-treated patients. The presence of ADAb was associated with lower EULAR response and lower drug levels compared with those without ADAb (both p<0.001). Drug trough levels were positively associated with DAS28 decrement (ΔDAS28) (all p<0.001). The optimal cut-off trough levels for adalimumab were 1.274 μg/mL and 1.046 μg/mL, and those for etanercept were 1.242 μg/mL and 0.800 μg/mL for good EULAR response assessed at the 6th and 12th month, respectively. CONCLUSIONS: ADAb levels were inversely correlated with therapeutic response and drug levels. The positive correlation between drug levels and ΔDAS28 indicates that drug monitoring would be useful to evaluate therapeutic response of TNF-α inhibitors.
24355439 Probiotic supplementation improves inflammatory status in patients with rheumatoid arthrit 2014 Apr OBJECTIVES: Rheumatoid arthritis (RA) is an inflammatory autoimmune disease in which the gut microbiota is altered. Probiotics are microorganisms that can normalize gut microbiota; thus, they may help to alleviate RA symptoms. The objective of the present clinical trial was to assess the effects of probiotic supplementation on disease activity and inflammatory cytokines in patients with RA. METHODS: Forty-six patients with RA were assigned into two groups in this randomized, double-blind, placebo-controlled clinical trial. The patients in the probiotic group received a daily capsule that contained a minimum of 10(8) colony-forming units of Lactobacillus casei 01 for 8 wk. The placebo group took capsules filled with maltodextrin for the same time period. Questionnaires, anthropometric measurements, and fasting blood samples were collected, and the participants were assessed by a rheumatologist at baseline and at the end of the trial. RESULTS: Disease activity score was significantly decreased by the intervention, and there was a significant difference between the two groups at the end of the study (P < 0.01). Three of the assessed serum proinflammatory cytokines (tumor necrosis factor-α, interleukin-6, and interleukin-12) significantly decreased in the probiotic group (P < 0.05); however, serum levels of interleukin-1 β were not significantly affected by the probiotic (P = 0.22). The serum level of regulatory cytokine (interleukin-10) was increased by the supplementation (P < 0.05). The proportion of interleukin-10 to interleukin-12 was significantly increased in the probiotic group as well. CONCLUSIONS: L. casei 01 supplementation improved the disease activity and inflammatory status of patients with RA. Further studies are warranted to confirm these results, and such confirmation may lead to the introduction of probiotics as adjunctive therapy for this population.
23649513 Host modulation in rheumatoid arthritis patients with TNF blockers significantly decreases 2013 Oct The aim of this study was to evaluate the effects of host modulation therapy on periodontal and biochemical parameters. Sixteen rheumatoid arthritis patients newly scheduled for anti-tumour necrosis factor (TNF) therapy were screened for 30 days. Periodontal parameters (clinical attachment level, probing pocket depth, bleeding on probing, plaque index and gingival index) as well as salivary and gingival crevicular fluid (GCF), interleukin (IL)-1β, IL-8 and monocyte chemoattractant protein-1 (MCP-1) levels of the patients were evaluated at baseline and on the 30th day of therapy. GCF volume, IL-1β and IL-8 levels (p = 0.007, p = 0.017 and p = 0.009, respectively) of the periodontitis patients significantly decreased. Although there was a decrease in all these parameters in healthy patients, it was below statistical significance. Salivary IL-8 and MCP-1 levels significantly decreased in periodontitis patients (p = 0.028 and p = 0.013, respectively), but IL-1β levels remained unchanged. These results suggest that TNF blockers may significantly modify host response in terms of biochemical parameters of the periodontium and may mask significant associations such as those reported between periodontitis and rheumatoid arthritis.
24839031 Patient and physician expectations of add-on treatment with golimumab for rheumatoid arthr 2014 Dec OBJECTIVE: Rheumatoid arthritis (RA) management involves improving clinical outcomes and quality of life (QOL). Golimumab is used as add-on therapy for patients who have failed disease-modifying antirheumatic drugs (DMARDs). This GO-MORE subanalysis investigated relationships between patient and physician expectations and outcomes. METHODS: GO-MORE was an open-label, multinational, prospective study in biologic agent-naive patients with active RA despite DMARD treatment. Patients received 50 mg subcutaneous golimumab monthly for 6 months. At baseline and month 3, patients rated treatment expectations for the following 3 months using 5-point scales (where 1 = good and 5 = poor). Outcomes were compared among expectation tertiles: most positive, intermediate, and least positive. At baseline and month 3, physicians predicted patient disease state 3 months later. RESULTS: At baseline, 3,280 efficacy-evaluable patients with moderate (21.3%) or high (78.7%) disease activity had mean ± SD disease duration of 7.6 ± 7.9 years, mean ± SD Health Assessment Questionnaire (HAQ) disability index (DI) score of 1.44 ± 0.67, and mean ± SD EuroQol 5-domain (EQ-5D) score of 0.42 ± 0.33. Patients reported high treatment expectations (mean 1.43); 95.9% expected golimumab to be better than current treatment. Patients with fewer DMARD failures, higher disease activity, shorter disease duration, younger age, and female sex reported higher expectations (P < 0.05 for all). After 6 months, patients with the most positive expectations had higher remission rates (P < 0.0001) and greater HAQ DI (P < 0.0001) and EQ-5D (P < 0.0001) score improvements. At baseline, physicians expected 29.6% and 59.2% of patients to attain remission and low disease activity, respectively, after 3 months. CONCLUSION: Patients had high expectations for golimumab treatment. Patients with more positive expectations had greater remission rates, improvements in function, and QOL.
22514156 Contribution of obesity to the rise in incidence of rheumatoid arthritis. 2013 Jan OBJECTIVE: Obesity is an underrecognized risk factor for rheumatoid arthritis (RA). In recent years, both the prevalence of obesity and the incidence of RA have been rising. Our objective was to determine whether the "obesity epidemic" could explain the recent rise in the incidence of RA. METHODS: An inception cohort of Olmsted County, Minnesota residents who fulfilled the 1987 American College of Rheumatology criteria for RA in 1980-2007 was compared to population-based controls (matched on age, sex, and calendar year). Heights, weights, and smoking statuses were collected from medical records. Obesity was defined as a body mass index ≥30 kg/m(2) . Conditional logistic regression was used to assess the influence of obesity on developing RA. Population attributable risk was used to estimate the incidence of RA in the absence of obesity. RESULTS: The study included 813 patients with RA and 813 controls. Both groups had extensive medical history available prior to the incidence/index date (mean 32.2 years), and ~30% of each group was obese at the incidence/index date. The history of obesity was significantly associated with developing RA (odds ratio 1.24, 95% confidence interval 1.01-1.53; adjusted for smoking status). In 1985-2007, the incidence of RA rose by an increment of 9.2 per 100,000 among women. Obesity accounted for 4.8 per 100,000 (52%) of this increase. CONCLUSION: Obesity is associated with a modest risk for developing RA. Given the rapidly increasing prevalence of obesity, this has had a significant impact on RA incidence and may account for much of the recent increase in the incidence of RA.
23824148 Immunomodulatory effects of vitamin D in peripheral blood monocyte-derived macrophages fro 2014 Aug 1,25-Dihydroxyvitamin D (1,25(OH)2D3), the active form of vitamin D, modulates both innate and adaptive immune responses. Emerging epidemiological data has also demonstrated disease-modifying and immunomodulatory effects of vitamin D in a wide range of human autoimmune diseases, including rheumatoid arthritis (RA). To evaluate in vitro effects of 1,25(OH) 2D3 in primary cultures of peripheral blood monocyte-derived macrophages of RA patients, monocyte/macrophages, isolated from peripheral blood mononuclear cells of RA patients and healthy subjects by exploiting their ability to adhere to plastic, were treated with increasing concentrations of 1,25(OH)2D3 for 48 h. TNF-α, IL-1 α, IL-1β, IL-6 and RANKL production was determined by ELISA and nitric oxide (NO) release using the Griess method. Immunocytochemistry analysis was also performed to evaluate alterations in transmembrane TNF-α expression after 1,25(OH) 2D3 treatment. A significant dose-dependent decrease in TNF-α and RANKL production by cultured RA macrophages after 1,25(OH)2D3 treatment was found, whereas a significant reduction in normal cells was observed only at higher concentrations. IL-1 α, IL-1β and IL-6 levels were reduced by 1,25(OH) 2D3 at higher concentrations in all cell populations. TNF-α immunostaining was less intense in treated cells compared with untreated. 1,25(OH) 2D3 significantly reduced NO levels regardless of the concentration used. Vitamin D downregulated proinflammatory mediators in monocyte-derived macrophages, and RA cells appeared more sensitive than normal cells. These effects further provide a rationale for the therapeutic value of vitamin D supplementation in the treatment for RA.
23568741 [Association between polymorphisms of PSMB8, PSMB9 and TAP2 genes with rheumatoid arthriti 2013 Apr OBJECTIVE: To assess the association between single nucleotide polymorphisms (SNPs) of PSMB8, PSMB9 and TAP2 genes and rheumatoid arthritis (RA) in ethnic Han Chinese from Yunnan. METHODS: A case-control study was carried out using 177 RA patients and 288 healthy controls. Genotypes of rs2071543, rs55745125 and rs138635403 loci of PSMB8 gene, and rs17587 locus of PSMB9 gene were determined with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). And a polymerase chain reaction amplification refractory mutation system (ARMS-PCR) was used for typing rs2228396 locus of TAP2 gene. Genotypic and allelic frequencies were calculated. An Epi Info 7 software was used to calculate the Odds Ratio (OR) of above SNPs between the two groups. RESULTS: Allelic and genotypic frequencies of rs138635403 and rs17587 loci have differed significantly between the two groups (P<0.05). The frequency of GG genotype for rs17587 locus was also higher in the RA group (0.672) compared with control group (0.524) (OR=1.862, 95%CI: 1.261-2.749). CONCLUSION: Genetic polymorphisms of rs17587 appeared to be associated with RA in ethnic Han Chinese from Yunnan.
24660421 Periodontal disease: Mechanisms of infection and inflammation and possible impact on misce 2013 Nov Periodontitis is a chronic inflammatory disease, resulting from a predominantly gram-negative microbial infection within the sub-gingival dental plaque biofilm. The resulting inflammatory response in the periodontal tissues may facilitate intravascular dissemination of micro-organisms and their products, throughout the body. The total surface area of this inflammatory field is estimated to be the size of the palm of the hand. A skin lesion of this size would prompt immediate medical intervention. However, the intra-oral (and similar-sized) infection is frequently ignored by health professionals, despite the fact that it may be associated with a range of systemic diseases/conditions.
25128482 The effect of CTLA-4 A49G polymorphism on rheumatoid arthritis risk: a meta-analysis. 2014 Aug 16 BACKGROUND: Recently, a number of studies have been performed to explore the association between CTLA-4 A49G polymorphism and rheumatoid arthritis (RA). However, the results of previous works are still controversial and ambiguous. METHODS: In this work, we attempted to perform an updated meta-analysis of available case-control study in order to assess the association between CTLA-4 A49G polymorphism and RA risk. We searched the various citation databases without limits on languages. Article searching was performed by screening the references of retrieved studies manually. Odds ratios (OR) and 95% confidence intervals (95% CI) were calculated to evaluate the strength of the association. RESULTS: We totally compiled 27 studies in 24 articles (9805 RA patients and 10691 control subjects) into our meta-analysis work. We found significant association between CTL-A4 A49G polymorphism and RA risk (GG vs. AA: OR = 1.13, 95% CI = 1.03-1.23; GA vs. AA: OR = 1.19, 95% CI = 1.07-1.33; GA + GG vs. AA: OR = 1.18, 95% CI = 1.07-1.29). In the subgroup analysis by ethnicity, evidences of significantly increased risk was also found in both Asian (GG vs. AA: OR = 1.34, 95% CI = 1.15-1.55; GA + GG vs. AA: OR = 1.24, 95% CI = 1.08-1.41) and Caucasian population (GA vs. AA: OR = 1.19, 95% CI = 1.03-1.37; GA + GG vs. AA: OR = 1.14, 95% CI = 1.01-1.29). No evidence of publication bias was found in this work. CONCLUSIONS: Our meta-analysis suggests that CTLA-4 A49G polymorphism was associated with RA risk. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/13000_2014_157.
23244167 MSRA polymorphism is associated with the risk of rheumatoid arthritis in a Chinese populat 2013 OBJECTIVES: The expression of receptor activator of methionine sulfoxide reductase A (MSRA) and that of receptor activator of nuclear factor-kappa B (NF-κB) ligand (RANKL) are closely related to rheumatoid arthritis (RA). Our aim was to confirm whether MSRA and RANKL polymorphisms play a role in RA in a Chinese population. METHODS: We investigated the presence of MSRA rs10903323 G/A and RANKL rs7984870 C/G polymorphisms in 329 patients with RA and 697 controls in a Chinese population. Genotyping was performed using matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). RESULTS: When the MSRA rs10903323 GG homozygote genotype was used as the reference group, the GA genotype was associated with a significantly increased risk for RA. In the dominant model, when the MSRA rs10903323 GG homozygote genotype was used as the reference group, the GA/AA genotypes were associated with a significantly increased susceptibility to RA. The RANKL rs7984870 C/G polymorphism was not associated with a risk for RA. In stratification analyses, a significantly increased risk for RA associated with the MSRA rs10903323 GA genotype was evident among male patients, older patients, C-reactive protein (CRP)-positive patients, and anti-cyclic citrullinated peptide (anti-CCP) negative patients compared with the MSRA rs10903323 GG genotype. CONCLUSIONS: These findings suggest that the MSRA rs10903323 G/A variant allele is associated with RA development, especially among male patients, older patients, CRP-positive patients, and anti-CCP negative patients.
23747721 CD45RA-Foxp3(high) activated/effector regulatory T cells in the CCR7 + CD45RA-CD27 + CD28+ 2013 Sep 6 Human CD4+ T cells can be classified as either naïve, central memory (TCM), or effector memory (TEM) cells. To identify the CD4+ T cell subsets most important in the pathogenesis of rheumatoid arthritis (RA), we phenotypically defined human CD4+ T cells as functionally distinct subsets, and analyzed the distribution and characteristics of each subset in the peripheral blood. We classified CD4+ T cells into six novel subsets based on the expression of CD45RA, CCR7, CD27, and CD28. The CCR7 + CD45RA-CD27 + CD28+ TCM subset comprised a significantly smaller proportion of CD4+ T cells in RA patients compared to healthy controls. The frequency of TNF-α-producing cells in the CCR7-CD45RA-CD27 + CD28+ TEM subset was significantly increased in RA. Furthermore, within the CCR7 + CD45RA-CD27 + CD28+ TCM subset, which was decreased in periperal blood from RA, the proportions of total Foxp3+ Treg cells and CD45RA-Foxp3(high) activated/effector Treg cells were significantly lower in RA patients. Our findings suggest that the increased proportion of TNF-α-producing cells and the decreased proportion of CD45RA-Foxp3(high) activated/effector Treg cells in particular subsets may have critical roles in the pathogenesis of RA.
24365061 Comparison of remission criteria in a tumour necrosis factor inhibitor treated rheumatoid 2013 Dec 24 INTRODUCTION: Our objectives were to assess the frequency and sustainability of American College of Rheumatology (ACR)/European League against Rheumatism (EULAR) and Disease Activity Score (DAS)28(4v)-C-reactive protein (CRP) remission 12 months after the initiation of tumour necrosis factor inhibitor (TNFi) therapy in a rheumatoid arthritis (RA) cohort. METHODS: Data were collected of 273 biologic naive RA patients at baseline, then 3, 6 and 12 months post-TNFi therapy. Remission status was calculated using DAS28(4v)-CRP <2.6 and ACR/EULAR Boolean criteria. Response was scored using EULAR criteria. RESULTS: Mean (range) patient age was 59.9 (7.2-85.4) years with disease duration of 13.4 (1.0-52.0) years. Responder status maintained from 3-12 months (86%, 82.4%), laboratory/clinical parameters (erythrocyte sedimentation rate (ESR), CRP, patient global health (PGH), DAS28(4v)-CRP) also showed sustained improvement (P < 0.05). DAS28 remission was reached by 102 subjects at 1 year, 27 patients were in Boolean remission, but 75 missed it from the DAS28 remission group. Patients in remission were younger (P = 0.041) with lower baseline tender joint count (TJC)28 and PGH than those not in remission (P = 0.001, P = 0.047). DAS28 remission patients were older (P = 0.026) with higher 12 months PGH and subsequently higher DAS28 than Boolean remission patients (P < 0.0001). Patients not achieving Boolean remission due to missing one subcriteria most frequently missed PGH ≤1 criteria (79.8%). CONCLUSIONS: Only 10% of this TNFi treated cohort achieved remission according to the new ACR/EULAR criteria, which requires lower disease activity. More stringent criteria may ensure further resolution of disease activity and better longterm radiographic outcome, which supports earlier intervention with biologic therapy in RA.
24152421 Dose REduction strategy of subcutaneous TNF inhibitors in rheumatoid arthritis: design of 2013 Oct 24 BACKGROUND: Preliminary, mostly uncontrolled studies suggest that dose reduction or discontinuation of tumour necrosis factor blockers can be achieved in a relevant proportion of patients with RA without loss of disease control. However, long term safety, cost effectiveness and feasibility in clinical practice remain uncertain. METHODS/DESIGN: This study is a 18-months pragmatic, non-inferiority, cost minimalisation, randomized controlled trial on dose reduction and discontinuation of the subcutaneous tumour necrosis factor (TNF) blockers adalimumab and etanercept in RA patients with low disease activity. 180 RA patients with low disease activity (DAS28 < 3.2 or clinical judgment of the rheumatologist) are randomized 2:1 to either increased spacing and eventually discontinuation after 6 months of the TNF blocker, and usual care. Implementation is done in routine daily care, using treat to target and feedback implementation in both treatment arms. The primary outcome is non-inferiority (NI margin 20%) in cumulative incidence of persistent (> 3 months) RA flare, according to a recently validated DAS28 based flare criterion (DAS28 change > 1.2, or DAS28 increase of 0.6 and current DAS28 ≥ 3.2). Secondary outcomes include mean disease activity, function, radiographic progression, safety and cost effectiveness. Cost per quality adjusted life year (QALY) differences between groups are expressed as a decremental cost effectiveness ratio (DCER), i.e. saved costs divided by (possible) loss in QALY. DISCUSSION: The design of this study targeted several clinical and methodological issues on TNF blocker dose de-escalation, including how to taper the TNF blockers, the satisfactory control condition, how to define flare, implementation in clinical practice, and the choice of the non-inferiority margin. Pragmatic cost minimalisation studies using non-inferiority designs and DCERs will become more mainstream as cost effectiveness in healthcare gains importance. TRIAL REGISTRATION: Dutch Trial Register NTR3216, The study has received ethical review board approval (number NL37704.091.11).
23809300 Diagnostic imaging for temporomandibular disorders and orofacial pain. 2013 Jul The focus of this article is diagnostic imaging used for the evaluation of temporomandibular disorders and orofacial pain patients. Imaging modalities discussed include conventional panoramic radiography, panoramic temporomandibular joint imaging mode, cone beam computed tomography, and magnetic resonance imaging. The imaging findings associated with common diseases of the temporomandibular joint are presented and indications for brain imaging are discussed. Advantages and disadvantages of each imaging modality are presented as well as illustrations of the various imaging techniques.
24782176 RFC1 80G>A is a genetic determinant of methotrexate efficacy in rheumatoid arthritis: a hu 2014 May OBJECTIVE: Associations have been reported between candidate genes and the response to methotrexate (MTX) in rheumatoid arthritis (RA) patients, but most of the studies have been small and have yielded conflicting results. This study was undertaken to provide a systematic review of all genetic variant associations with MTX efficacy and toxicity, and to conduct a meta-analysis evaluating the most commonly studied single-nucleotide polymorphism for which prior cumulative analysis has been lacking. METHODS: A systematic review and meta-analysis were performed to identify genetic variant associations with MTX efficacy and toxicity. Studies were identified from the Medline, EMBase, HuGENet Navigator, and Cochrane Library databases through December 2012, and from the 2009-2011 abstracts of the American College of Rheumatology and the European League Against Rheumatism annual meeting proceedings. Additional unpublished genotype data from a Canadian cohort of patients with early RA were also included. RESULTS: Among the 87 identified studies examining genetic associations with MTX efficacy and toxicity, the reduced folate carrier 1 gene (RFC1) variant 80G>A (Arg(27) His, rs1051266) was selected for random-effects meta-analysis. RFC1 80G>A was associated with MTX efficacy in both the recessive model (odds ratio [OR] 1.42, 95% confidence interval [95% CI] 1.04-1.93) and the additive model (OR 1.28, 95% CI 1.10-1.49). Restriction of the sensitivity analyses to studies that involved Caucasian subjects only and that used similar outcome measures (MTX failure versus nonfailure) maintained and improved the associations in both models. No significant association between RFC1 80G>A and MTX toxicity was detected. CONCLUSION: In these analyses of available data from observational studies, RFC1 80G>A was found to be associated with MTX efficacy, but not toxicity, in RA patients. This variant merits further prospective analysis as a potential predictor of MTX efficacy. Variability in the definitions of response in pharmacogenetic studies is a source of data heterogeneity that should be addressed.
25229610 Rheumatoid arthritis and the risk of bipolar disorder: a nationwide population-based study 2014 BACKGROUND: Studies have suggested that chronic inflammation plays an essential role in the pathophysiology of both rheumatoid arthritis (RA) and bipolar disorder. The most common clinical features associated with RA are anxiety and depression. The risk of bipolar disorder among patients with RA has not been characterized adequately. OBJECTIVE: To determine the association between RA and the subsequent development of bipolar disorder and examine the risk factors for bipolar disorder among patients with RA. METHODS: We identified patients who were diagnosed with RA in the Taiwan National Health Insurance Research Database. A comparison cohort was created by matching patients without RA with those with RA according to age, sex, and comorbidities. The occurrence of bipolar disorder was evaluated in both cohorts. RESULTS: The RA cohort consisted of 2,570 patients, and the comparison cohort consisted of 2,570 matched control patients without RA. The incidence of bipolar disorder (incidence rate ratio  = 2.13, 95% confidence interval [CI]  = 1.12-4.24, P =  .013) was higher among patients with RA than among control patients. Multivariate, matched regression models revealed that asthma (hazard ratio [HR]  = 2.76, 95% CI 1.27-5.96, P =  .010), liver cirrhosis (HR  = 3.81, 95% CI  = 1.04-14.02, P =  .044), and alcohol use disorders (HR  = 5.29, 95% CI  = 1.71-16.37, P =  .004) were independent risk factors for the development of bipolar disorder among patients with RA. CONCLUSION: RA might increase the incidence of bipolar disorder development. Based on our data, we suggest that, following RA diagnosis, greater attention be focused on women with asthma, liver cirrhosis, and alcohol use disorder. Prospective clinical studies of the relationship between RA and bipolar disorder are warranted.
24337323 Adjacent-level failures after occipito-thoracic fusion for rheumatoid cervical disorders. 2014 Mar INTRODUCTION: The natural history of cervical spine lesions in rheumatoid arthritis (RA) is variable. We have actively performed occipito-thoracic fusion for severe destructive rheumatoid cervical disorders and reported its clinical results and complications. In our previous study, the most frequent complication was the adjacent-level failures caused by the fragile spine. The objective of this study was to determine risk factors for adjacent-level failures after occipito-thoracic fusion. MATERIALS AND METHODS: Subjects were 35 RA patients (31 females and 4 males) who underwent occipito-thoracic fusion using RRS Loop Spinal System(®) (Robert Reid Inc. Tokyo, Japan), and the incidence and characteristics of adjacent-level failures were investigated. Furthermore, the adjacent-level failures were divided into two types according to their levels, fracture at the lowest level of the fusion area and that at the level inferior to the fusion area, and the characteristics of each type were evaluated. RESULTS AND CONCLUSION: Nine (26%) of 35 patients suffered adjacent-level failures (10 vertebral fractures). Adjacent-level failures occurred when the distance of fixation was "O-T4" or longer. The long fusion might cause adjacent-level failures due to greater mechanical stress. Seven fractures occurred at the lowest level of the fusion area, and all of them were cured without symptoms by conservative treatment. Three fractures occurred at the level inferior to the fusion area, and one of them needed additional surgery due to sudden paraplegia resulting from collapse of the adjacent vertebra. After occipito-thoracic fusion, burst fractures at the level inferior to the fusion area might cause sudden paraplegia, and therefore a careful observation should be required for patients with these fractures.
24767864 Oncostatin M acting via OSMR, augments the actions of IL-1 and TNF in synovial fibroblasts 2014 Aug OBJECTIVE: To identify how the gp130-signaling cytokine oncostatin M (OSM), acting alone or in concert with IL-1β or TNFα, affects synovial fibroblast expression of genes relevant to inflammation and bone erosion in inflammatory arthritis. METHODS: Synovial fibroblasts (SFs) were isolated from non-arthritic wild type (WT) or OSM receptor deficient (OSMR(-/-)) mice and stimulated with OSM, IL-1β or TNFα and their combinations. Cytokine gene expression was assessed by quantitative RT-PCR. ELISA, flow cytometry and immunohistochemistry identified protein expression. Gene expression patterns were confirmed in SFs isolated from patients with osteoarthritis (OASFs) and rheumatoid arthritis (RASFs). RESULTS: Expression of OSM and its receptors, gp130, OSMR and LIFR, was increased in synovial tissue from the mouse antigen-induced arthritis model. In isolated WT mouse synovial fibroblasts OSM alone, or in synergy with IL-1β, or together with TNFα, potently induced expression of the pro-inflammatory cytokine IL-6. OSM also induced a sustained increase in mRNA levels of the pro-osteoclastic cytokine RANKL. Combining OSM with IL-1β, but not with TNFα, further increased RANKL expression. Importantly these effects of OSM were all dependent on the expression of OSMR. Furthermore, OSM also increased expression of its own receptors, gp130 and OSMR and the IL-1 receptor, IL1-R1; the latter effects were also observed in both human OASFs and RASFs. CONCLUSION: Together our data suggests that OSM signaling via OSMR in SFs has the potential to contribute significantly to joint destruction in inflammatory arthritis. It not only induces expression of pro-inflammatory and pro-osteoclastic cytokines but can also augment its own actions and that of IL-1 by inducing expression of OSMR and IL-1R1.
23324280 Programmed cell death 5 correlates with disease activity and interleukin-17 in serum and s 2013 Jan BACKGROUND: Programmed cell death 5 (PDCD5) is a novel apoptotic regulatory gene that promotes apoptosis in various tumor cells. Studies have shown that PDCD5 accelerates the apoptosis of synoviocytes in vitro, implying a potential role in rheumatoid arthritis (RA) pathogenesis. This study examined the expression of PDCD5 in serum and synovial fluid of RA patients, its effect on the expression of inflammatory cytokine, interleukin-17 (IL-17), and the assessment of disease activity in RA. METHODS: PDCD5 and IL-17 levels in serum and synovial fluid from 18 patients with RA and 22 patients with osteoarthritis (OA) were detected using enzyme-linked immunosorbent assay (ELISA). Concentrations of serum PDCD5 in 40 healthy people were also detected as controls. As disease activity indices, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), rheumatoid factor (RF), and X-ray grading scale were also evaluated. RESULTS: Serum and synovial fluid PDCD5 levels in RA patients were significantly higher than those in OA and healthy controls. Serum PDCD5 level was inversely correlated to CRP and ESR, and was significantly higher in the RF negative group than in the positive group. PDCD5 level was also negatively correlated with IL-17 levels both in serum and synovial fluid of RA patients. However, differences in synovial fluid PDCD5 level from RA patients at different Larsen stages were not detectable. CONCLUSIONS: PDCD5 affects RA pathogenesis. Insufficient apoptosis of fibroblast-like synoviocytes and inflammatory cells in RA could increase the expression of PDCD5 protein. As PDCD5 levels correlated negatively with disease activity indices and IL-17 level, PDCD5 could become a target in the diagnosis and treatment of RA.