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ID PMID Title PublicationDate abstract
22210852 A tight control treatment strategy aiming for remission in early rheumatoid arthritis is m 2012 Jun There is strong evidence from clinical trials that a 'treat to target' strategy is effective in reaching remission in rheumatoid arthritis (RA). However, the question is whether these results can be translated into daily clinical practice and clinical remission is a reachable target indeed. OBJECTIVE: The study aims to investigate whether in early RA a treatment strategy aiming at Disease Activity Score (DAS) 28 <2.6 is more effective than 'usual care' treatment for reaching clinical remission after 1 year. METHODS: Two early RA inception cohorts from two different regions including patients who fulfilled the American College of Rheumatology criteria for RA were compared. Patients in the tight-control cohort (n=126) were treated according to a DAS28-driven step-up treatment strategy starting with methotrexate, addition of sulphasalazine (SSZ) and exchange of SSZ by anti-tumour necrosis factor in case of failure. Patients in the usual-care cohort (n=126) were treated with methotrexate or SSZ, without DAS28-guided treatment decisions. The primary outcome was the percentage remission (DAS28<2.6) at 1 year. Time to first remission and change in DAS28 were secondary outcomes. RESULTS: After 1 year, 55% of tight-control patients had a DAS28<2.6 versus 30% of usual care patients (OR 3.1, 95% CI 1.8 to 5.2). The median time to first remission was 25 weeks for tight control and more than 52 weeks for usual care (p<0.0001). The DAS28 decreased with -2.5 in tight control and -1.5 in usual care (p<0.0001). CONCLUSION: In early RA, a tight control treatment strategy aiming for remission leads to more rapid DAS28 remission and higher percentages of remission after 1 year than does a usual care treatment.
22354681 The indirect antinociceptive mechanism of 15d-PGJ2 on rheumatoid arthritis-induced TMJ inf 2012 Sep BACKGROUND: Inflammation of the temporomandibular joint (TMJ) induced by rheumatoid arthritis (RA) have resulted in persistent pain and caused distress to many patients. Considering that not all patients respond to traditional drugs therapy to RA and it has demonstrated that 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) into TMJ has a potential peripheral antinociceptive effect, the aim of this study was to evaluate the peripheral effect of 15d-PGJ2 in RA-induced TMJ inflammatory hypernociception. METHODS: Antigen-induced arthritis (AIA) was generated in rats with methylated bovine serum albumin (mBSA). RA-induced TMJ hypernociception was assessed by measuring the behavioural nociceptive responses. After behavioural experiments, the animals were terminally anaesthetized and periarticular tissues were removed and homogenized. The supernatants were used to evaluate the levels of tumour necrosis factor (TNF)-α, interleukin (IL)-1β and keratinocyte-derived chemokine (KC) by enzyme-linked immunosorbent assay as well the expression of PKCε and PKA by western blotting analysis. RESULTS: The intra-articular injection of mBSA, but not phosphate buffered saline (control), in immunized rats induced dose- and time-dependent behavioural nociceptive responses in which the peak of nociceptive responses were obtained by using 10 μg/TMJ of mBSA after 24 h. Pretreatment with 15d-PGJ2 (30, 100 and 300 ng/TMJ) inhibited the RA-induced TMJ inflammatory hypernociception. In addition, 15d-PGJ2 reduced the RA-induced release of TNF-α, IL-1β and KC (p < 0.05) as well the expression of PKA and PKCε (p < 0.05). CONCLUSIONS: In the present study, we demonstrated that 15d-PGJ2 was able to reduce the RA-induced TMJ inflammatory hypernociception by an indirect mechanism. This antinociceptive effect is in part due to decrease of TNF-α, IL-1β and KC levels and PKA/PKCε expression in the TMJ.
22529523 Biomarkers of subclinical atherosclerosis in patients with autoimmune disorders. 2012 Atherosclerosis is accelerated in rheumatoid arthritis (RA) and psoriatic arthritis (PsA). We investigated a possible association of oxidized low-density lipoproteins (ox-LDLs), nitric oxide (NO), 3-nitrotyrosine, vitamin A, vitamin E, and β-carotene serum levels with subclinical atherosclerosis in RA and PsA. By the use of ELISA, we observed higher ox-LDL levels in patients with intima-media thickness (IMT) > 1 than in patients with IMT ≤ 1 and a negative correlation between NO levels and IMT values. By the use of high-performance liquid chromatography, we determined higher levels of vitamin A in patients with PsA and IMT ≤ 1 than in controls and lower levels of β-carotene in patients with RA and PsA than in controls. β-carotene concentrations were negatively correlated to the duration of disease in RA. Our study confirms that ox-LDLs and NO may be markers of accelerated atherosclerosis in RA and PsA whereas vitamins seem to be associated only to the presence of the autoimmune disorders.
21219548 Opinion of Japanese rheumatology physicians on methods of assessing the quality of rheumat 2012 Apr OBJECTIVE: To examine the opinion of rheumatology physicians in Japan regarding desirable quality assessment methods. METHODS: We conducted a cross-sectional self-administered mail survey on a random sample of physicians and surgeons registered with the Japan Rheumatism Foundation. In the survey, respondents were asked to rank seven proposed assessment methods for the quality of rheumatoid arthritis care, namely patient satisfaction, risk-adjusted outcomes such as complication incidence and admission rate, guideline compliance, waiting time at clinics, voting by local general practitioners, degree of newspaper and magazine reportage, and volume of patients receiving treatment for rheumatoid arthritis. RESULTS: Among 531 respondents (response rate 48%), the respondents ranked patient satisfaction most favourably (mean rank 1.6), followed by complication/admission rate and number of patients. Guideline adherence was ranked almost the same as voting by local physicians. Waiting time and media reportage were not considered good methods for quality evaluation. Ranking distribution did not differ by working facility or place, volume of patients or years in practice. Multivariate analysis revealed that respondents who care for a large number of rheumatoid arthritis patients (>40 regular patients) were less likely to rank guideline adherence highly (first to third) than those who care for few patients (≤ 10 regular patients), with an odds ratio of 0.38 (P < 0.01) after adjustment for other variables. CONCLUSIONS: A majority of Japanese rheumatology physicians consider patient satisfaction the most trustworthy method of assessing the quality of rheumatoid arthritis care. Future research should explore convincing methods of assessing the technical quality of rheumatoid arthritis care.
22830352 Protein kinase C-theta inhibitors: a novel therapy for inflammatory disorders. 2012 PKC-θ is a serine/threonine specific protein kinase and its activation depends upon the concentration of diacylglycerol (DAG) and phospholipids (phosphatidylserine). PKC-θ phosphorylates a variety of proteins that are known to be involved in the diverse cellular signaling pathways. It is predominantly expressed in the T-cells and localized in the center of immunological synapse upon T-cell receptor (TCR) and CD28 signaling. Activation of PKC-θ leads to the activation of various transcription factors in the nuclei of T-cells, e.g. NF-κB, NFAT, c-Jun, c-Fos and AP-1 that further control the proliferation and differentiation of T-cells. Defective T-cell activation in turn leads to the aberrant expression of apoptosis related proteins that cause the poor T-cell survival. Researchers have found that T-cells deficient in PKC-θ exhibit reduced interleukin-2 (IL-2) production. Apart from this role on IL-2 expression, it also plays crucial roles in the proliferation, differentiation and survival of the T-cells, which make it an attractive therapeutic target for a variety of immunological and T-cell mediated diseases. Hence, new molecules capable of modulating the expression or biological activity of PKC-θ are being developed and tested for their potential as novel therapy for several T-cells mediated disease conditions such as multiple sclerosis, rheumatoid arthritis, asthma, inflammatory bowel disease and organ transplantation, etc. In the present review, we tried to integrate the recent discoveries on PKC-θ including its pharmacology and therapeutic potential, along with brief update on its inhibitor molecules.
22971156 Selective JAK1 inhibitor and selective Tyk2 inhibitor patents. 2012 Oct INTRODUCTION: The JAK family comprises of the four non-receptor tyrosine kinases JAK1, JAK2, JAK3 and Tyk2, which play key, but differing, roles in cytokine receptor signal transduction. A non-selective JAK inhibitor, ruxolitinib, has recently been approved to treat myelofibrosis whereas tofacitinib is poised for approval to treat rheumatoid arthritis. Selective inhibition of JAK3, JAK1 or Tyk2 provides the opportunity to achieve clinical efficacy in the treatment of inflammatory diseases while reducing the risk of dose-limiting effects attributable to JAK2 inhibition. AREAS COVERED: This review considers the small number of published patent filings that claim either selective JAK1 or selective Tyk2 inhibitors. These are considered in the context of the considerably larger number of disclosures and patent filings claiming selective JAK2 or JAK3 inhibitors. EXPERT OPINION: The recent disclosure of the clinical efficacy of a selective JAK1 inhibitor (GLPG-0634) in rheumatoid arthritis and detailed disclosure of the some potent and highly selective JAK1 inhibitors provide a clear stimulus for further activity in this area. The availability of a selective Tyk2 inhibitor will provide the opportunity for better understanding of the physiological role of this kinase. Recent patent applications indicate that Tyk2 selectivity is achievable and Tyk2 inhibitors have potential in the treatment of multiple sclerosis.
21753787 DNA methylation regulates the expression of CXCL12 in rheumatoid arthritis synovial fibrob 2011 Dec In the search for specific genes regulated by DNA methylation in rheumatoid arthritis (RA), we investigated the expression of CXCL12 in synovial fibroblasts (SFs) and the methylation status of its promoter and determined its contribution to the expression of matrix metalloproteinases (MMPs). DNA was isolated from SFs and methylation was analyzed by bisulfite sequencing and McrBC assay. CXCL12 protein was quantified by enzyme-linked immunosorbent assay before and after treatment with 5-azacytidine. RASFs were transfected with CXCR7-siRNA and stimulated with CXCL12. Expression of MMPs was analyzed by real-time PCR. Basal expression of CXCL12 was higher in RASFs than osteoarthritis (OA) SFs. 5-azacytidine demethylation increased the expression of CXCL12 and reduced the methylation of CpG nucleotides. A lower percentage of CpG methylation was found in the CXCL12 promoter of RASFs compared with OASFs. Overall, we observed a significant correlation in the mRNA expression and the CXCL12 promoter DNA methylation. Stimulation of RASFs with CXCL12 increased the expression of MMPs. CXCR7 but not CXCR4 was expressed and functional in SFs. We show here that RASFs produce more CXCL12 than OASFs due to promoter methylation changes and that stimulation with CXCL12 activates MMPs via CXCR7 in SFs. Thereby we describe an endogenously activated pathway in RASFs, which promotes joint destruction.
21558614 Psychological status is associated with health related quality of life in patients with rh 2011 OBJECTIVE: Rheumatoid arthritis (RA) is a chronic and disabling disease frequently effects physical and psychological well being. The aim of the present study was to determine the impact of psychological status on health related quality of life in patients with RA and also to assess which quality of life (QoL) instrument - disease specific and generic - is more prone to this effect. METHODS: A total of 421 patients with RA recruited from joint database of five tertiary centers. Depression and anxiety risks were assessed by the Hospital Anxiety and Depression Scale (HADS); and quality of life assessed by Rheumatoid Arthritis Quality of Life (RAQoL), Nottingham Health Profile (NHP) and The Short Form 36 (SF 36) questionnaire. RESULTS: Patients with higher risk for depression or anxiety had poorer quality of life compared to the patients without risk for depression or anxiety. Depression and anxiety scores significantly correlated with quality of life questionnaires. There was significant association between anxiety and depression with worsening in both disease specific and generic health related quality of life. However, RAQoL showed more association with depression and anxiety levels. CONCLUSION: Higher depression and anxiety risks showed increased deterioration in quality of life. Compared to generic QoL scales, RAQoL scale, a disease specific QoL instrument, is much more influenced by depression and anxiety.
22106834 Allograft inflammatory factor-1 gene polymorphisms in patients with rheumatoid arthritis. 2012 May AIM: Allograft inflammatory factor-1 (AIF-1) is a cytoplasmic, inflammation-responsive protein. The increased expression of AIF-1 in synovial tissues and fluid from rheumatoid arthritis (RA) patients has been detected. Several single-nucleotide polymorphisms have been identified in the AIF1 gene, among them three leading to changes in amino acid sequence. The aim of this study was to examine the association between AIF1 rs2259571:A>C, rs2736182:G>A, and rs13195276:C>T polymorphisms and RA. We examined 380 patients with RA and 376 control subjects. RESULTS: There were no statistically significant differences in distribution of rs2736182 and rs2259571 genotypes and alleles between RA patients and control group. Moreover, there were no significant associations with the age of disease diagnosis, rheumatoid factor, extra-articular manifestation, and anti-cyclic citrullinated peptide (CCP) antibodies, whereas the active form of RA (patients with disease activity score (DAS28)>2.4) was more frequently diagnosed in patients with rs2259571 CC genotypes compared with patients with AA genotype (p=0.007, odds ratio=2.30, 95% confidence interval=1.25-4.25). CONCLUSION: Our results suggest that the AIF1 rs2259571 CC genotype is associated with the active form of RA.
21045791 Emerging MRI methods in rheumatoid arthritis. 2011 Feb New MRI techniques have been developed to assess not only the static anatomy of synovial hyperplasia, bone changes and cartilage degradation in patients with rheumatoid arthritis (RA), but also the activity of the physiological events that cause these changes. This enables an estimation of the rate of change in the synovium, bone and cartilage as a result of disease activity or in response to therapy. Typical MRI signs of RA in the pre-erosive phase include synovitis, bone marrow edema and subchondral cyst formation. Synovitis can be assessed by T2-weighted imaging, dynamic contrast-enhanced MRI or diffusion tensor imaging. Bone marrow edema can be detected on fluid-sensitive sequences such as short-tau inversion recovery or T2-weighted fast-spin echo sequences. Detection of small bone erosions in the early erosive phase using T1-weighted MRI has sensitivity comparable to CT. Numerous MRI techniques have been developed for quantitative assessment of potentially pathologic changes in cartilage composition that occur before frank morphologic changes. In this Review, we summarize the advances and new directions in the field of MRI, with an emphasis on their current state of development and application in RA.
22674012 Association of anti-citrullinated vimentin and anti-citrullinated α-enolase antibodies wi 2012 Oct OBJECTIVE: To determine whether the anti-citrullinated vimentin peptide 60-75 (anti-Cit-vimentin) and the immunodominant anti-citrullinated α-enolase peptide 1 (anti-CEP-1) antibodies are associated with subsets of patients with rheumatoid arthritis (RA) independently of the associations between anti-cyclic citrullinated peptide (anti-CCP) antibodies and clinical features of RA. METHODS: The 3 antibody types were quantified by enzyme-linked immunosorbent assay (ELISA) in serum samples from 521 patients with RA and 173 healthy controls of Spanish ancestry. Genotypes for HLA-DRB1 alleles and rs2476601 in PTPN22 were available for these patients and controls plus an additional 106 healthy controls. A combined analysis of the 3 antibodies was conducted using stratified contingency tables and logistic regression models. RESULTS: A differential, particularly strong, and independent association was observed between the presence of anti-Cit-vimentin antibodies and the presence of shared epitope (SE) alleles, specifically in patients carrying 2 SE alleles, and between the presence of anti- Cit-vimentin antibodies and the prevalence of joint erosion. Associations were observed between anti-CEP-1 positivity and the presence of HLA-DRB1 and PTPN22 risk alleles and their additive interaction. These associations were not accounted for by the anti-CCP status. CONCLUSION: Our results indicate that the 2 antibodies against citrullinated peptides analyzed in this study add specific information beyond that obtained with the anti-CCP status. They define subgroups of patients with RA in which genetic factors have different weight and there is an observed difference in the prevalence of erosions.
21833520 Methotrexate for rheumatoid arthritis patients who are on hemodialysis. 2011 Dec Methotrexate (MTX) can be toxic to patients suffering from end stage renal disease (ESRD) on hemodialysis even at low doses. This increase in toxicity is more notable in terms of bone marrow suppression in the form of pancytopenia. Many methods of elimination including dialysis itself have been proven ineffective, and alternate treatments with anti-TNF alpha blockers can be considered.
21445357 Effects of GSTM1 in rheumatoid arthritis; results from the Swedish EIRA study. 2011 Mar 22 OBJECTIVE: Glutathione-S-transferases (GSTs) play an important role in tobacco smoke detoxification, interestingly approximately 50% of individuals in most human populations lack the gene GSTM1 due to copy number variation (CNV). We aimed to investigate GSTM1 CNV in Rheumatoid Arthritis (RA) in relation to smoking and HLA-DRB1 shared epitope; the two best known risk factors for RA and in addition, to perform subanalyses in patients where relations between variations in GSTM1 and RA have previously been described. METHODS: qPCR was performed using TaqMan Copy Number assays (Applied Biosystems) for 2426 incident RA cases and 1257 controls from the Swedish EIRA. Odds ratio (OR) together with 95% confidence intervals (CI) was calculated and used as a measure of the relative risk of developing RA. RESULTS: No association between RA and GSTM1 CNV was observed when analyzing whole EIRA. However, ≥1 copy of GSTM1 appears to be a significant risk factor for autoantibody positive RA in non-smoking females ≥60 years (OR: 2.00 95% CI: 1.07-3.74), a population where such relationships have previously been described. Our data further suggest a protective effect of GSTM1 in ACPA-negative smoking men (OR: 0.56 95% CI: 0.35-0.90). CONCLUSION: We assessed the exact number of GSTM1 gene copies in relation to development and severity of RA. Our data provide support for the notion that variations in copy numbers of GSTM1 may influence risk in certain subsets of RA, but do not support a role for GSTM1 CNV as a factor that more generally modifies the influence of smoking on RA.
21354845 Melittin enhances apoptosis through suppression of IL-6/sIL-6R complex-induced NF-κB and 2011 Oct OBJECTIVE: Resistance to apoptosis of fibroblast-like synoviocytes (FLS) is considered as a major characteristic in RA. This study was designed to identify whether melittin has a pro-apoptotic effect in IL-6/sIL6R-stimulated human FLS by investigating the expression of mitochondrial apoptosis-related genes, nuclear factor-κB (NF-κB), and signal transducer and activators of transcription (STAT) activation. METHODS: Cell viability was determined using a MTT assay after melittin treatment. Expressions of STAT3 and mitochondrial apoptosis-related genes induced by the IL-6/sIL-6R complex were determined by real time-polymerase chain reaction and western blotting. The expression of NF-κB p65 following IL-6 stimulation was determined by western blot analysis. The effects of melittin on the expression of apoptosis-related genes and the transcription factors NF-κB p65 and STAT3 were assessed in FLS. Apoptosis of FLS was determined by TUNEL-labeling to detect DNA strand breaks and DNA fragmentation assays. Caspase-3 activity was determined by a colorimetric assay. RESULTS: IL-6/sIL-6R induced the activation of the transcription factors, STAT3, NF-κB p65 (nucleus), and Bcl-2. Melittin increased the expression of pro-apoptosis-related molecules, namely caspase-3, caspase-9, Apaf-1, and cytosolic cytochrome c, in a dose-dependent manner after treatment with IL-6/sIL-6R. Melittin inhibited STAT3 activation, translocation of NF-κB p65 into the nucleus, and expression of anti-apoptotic genes such as Bcl-2 and mitochondrial cytochrome c. CONCLUSIONS: The pro-apoptotic effects of melittin likely result from inhibition of the activation of the transcription factors, STAT3 and NF-κB p65, and regulation of mitochondrial apoptosis-related genes. Melittin is thus a promising therapeutic option for RA as it induces apoptosis in apoptosis-resistant synoviocytes.
22538965 The anti-arthritic and anti-oxidative effect of NBD (6-nitro-1,3-benzodioxane) in adjuvant 2012 Aug OBJECTIVES: The present study evaluated the anti-arthritic and anti-oxidative effects of 6-nitro-1,3-benzodioxane in the adjuvant-induced arthritis model in rats. METHODS: Arthritis was induced in female rats by intradermal injection of MT37Ra. Arthritis was evaluated by arthritic score, body weight loss, paw volume measurement, and histological changes. The plantar test was used to evaluate the effect of NBD on hyperalgesia. RESULTS: The hyperalgesia (p < 0.0001) and hind paw inflammation (p < 0.034) was significantly decreased with parallel increase in the body weight of the NBD-treated (25 mg/kg) group compared to arthritic control rats. The antioxidant activity analysis demonstrated that the treatment of NBD significantly suppressed the levels of nitric oxide (p < 0.001) and peroxide (p < 0.002) with a significant increase in the glutathione (p < 0.021) compared to the arthritic control group. Since the IL-1β and TNF-α are key pro-inflammatory cytokines in arthritis, we therefore measured their levels in the serum samples. In comparison to the arthritic control group, the NBD treatment significantly reduced the levels of IL-1β (p < 0.003) and TNF-α (p < 0.026). CONCLUSION: Our results suggests that NBD is an anti-arthritic agent that not only reduces the severity of the disease process but also affects contributing factors of arthritic inflammation including free radicals and inflammatory cytokines production.
22290871 Confirmation of association of FCGR3B but not FCGR3A copy number with susceptibility to au 2012 Apr The FCGR locus encoding the low-affinity Fcγ receptors (FcγR) for immunoglobulin G has largely been missed by genome-wide association studies due to complications with structural variation and segmental duplication. Recently identified copy number variants (CNVs) affecting FCGR3A and FCGR3B have been linked to a number of autoimmune disorders. We have developed and validated a novel quantitative sequence variant assay in combination with an adapted paralogue ratio test to examine independent CNVs carrying FCGR3A and FCGR3B in rheumatoid arthritis (RA) compared with healthy volunteers (n = 1,115 and 654, respectively). Implementation of a robust statistical analysis framework (CNVtools) allowed for systematic batch effects and for the inherent uncertainty of copy number assignment, thus avoiding two major sources of false positive results. Evidence for association with neither duplications nor deletions of FCGR3A was found; however, in line with previous studies, there was evidence of overrepresentation of FCGR3B deletions in RA (odds ratio [OR] 1.50, P = 0.028), which was more apparent in rheumatoid factor positive disease (OR 1.61, P = 0.011). The level of FcγRIIIb, encoded by FCGR3B, expression on neutrophils was shown to correlate with gene copy number. Thus, our results may highlight an important role for neutrophils in the pathogenesis of RA, potentially through reduced FcγRIIIb-mediated immune complex clearance.
21362763 Magnetic resonance imaging of the rheumatic foot according to the RAMRIS system is reliabl 2011 Jun OBJECTIVE: In rheumatology, magnetic resonance imaging (MRI) is predominantly applied in the assessment and outcome measurement of rheumatoid arthritis (RA) in hands and wrists, leading to the development of the RAMRIS (RA-MRI-Scoring) system. It was initiated by the Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT). The RAMRIS system has not been applied widely in the measurement of feet. We investigated the interreader and intrareader agreement of the RAMRIS scoring system in the assessment of feet in RA. METHODS: Twenty-nine patients with RA who had radiological damage and/or arthritis underwent MRI. Two experienced readers independently read both complete sets. One reader read 6 random sets after the initial session, in order to assess the intrareader agreement. For evaluation of the intrareader and interreader reliability, quadratic-weighted κ scores were calculated per joint and lesion. RESULTS: For the forefeet, interreader scores were excellent, ranging from 0.77 (bone edema) to 0.95 (bone erosion). Hindfoot interreader agreement scores were highest for erosion (0.90) and synovitis global score (0.88), but edema and synovial thickness agreement were also acceptable (0.83 and 0.86). Intrareader scores were on the whole slightly lower, but excellent. CONCLUSION: Reliability (interreader and intrareader agreement) in the assessment of the rheumatoid foot according to the RAMRIS method is excellent.
22390577 Predictors of new atherosclerotic carotid plaque development in patients with rheumatoid a 2012 Mar 5 INTRODUCTION: Rheumatoid arthritis (RA) is associated with increased cardiovascular morbidity and mortality attributed to both classical risk factors and chronic inflammation. We assessed longitudinally the factors associated with new carotid plaques in nondiabetic RA patients and apparently healthy individuals. METHODS: In our present prospective observational study, carotid plaques were identified by ultrasonography at baseline and follow-up end, separated by an average of 3.6 ± 0.2 years, in 64 patients (mean age 59.2 ± 12.0 and disease duration at baseline 7.8 ± 6.2 years, 83% women, clinical and laboratory evaluation every 3 to 6 months). In a substudy, 35 of the patients were matched 1:1 for traditional cardiovascular risk factors with 'healthy' controls and were studied in parallel. RESULTS: New atherosclerotic plaques formed in 30% of patients (first plaque in 9%) who were significantly older than the remaining patients. Tobacco use, blood pressure, body mass index, average cumulative low-density lipoprotein, high-sensitivity C-reactive protein, erythrocyte sedimentation rate level, RA stage, functional class, disease duration and treatment modalities during follow-up did not differ significantly between subgroups after application of the Bonferroni correction. RA was in clinical remission, on average, for approximately 70% of the follow-up time and was not different between subgroups. Multivariate analysis including all the above parameters revealed that age (P = 0.006), smoking (P = 0.009) and duration of low-dose corticosteroid use (P = 0.016) associated independently with new plaque formation. RA patients displayed similar numbers of newly formed carotid plaques to the tightly matched for traditional cardiovascular risk factors 'healthy' controls, although more patients than controls had carotid plaques at baseline. CONCLUSIONS: Formation of new atherosclerotic plaques in this small cohort of patients with well-controlled RA depended mainly on traditional cardiovascular risk factors and corticosteroid use, whereas an adverse effect of residual systemic inflammation was not readily detectable.
23135613 Induced psoriasis after rituximab therapy for rheumatoid arthritis: a case report and revi 2013 Nov Rituximab is a human/murine monoclonal antibody targeting the CD20 antigen on B-lymphocytes surface. Although it has been licensed for treatment of non-Hodgkin's lymphoma, nowadays it is also a novel therapy for autoimmune diseases, such as rheumatoid arthritis and systemic lupus erythematosus. Despite the increasing evidence regarding the safety and efficacy of rituximab in these conditions, many cutaneous adverse events have been reported. Here, we describe the case of a 69-year-old patient, affected by rheumatoid arthritis, who developed psoriatic lesions on her trunk and arms, three months after the second course of rituximab. Similar cases appearing in the literature will also be briefly mentioned.
21517753 Indoleamine 2,3-dioxygenase as a modifier of pathogenic inflammation in cancer and other i 2011 Chronic inflammation underlies the basis for development and progression of cancers and a variety of other disorders, but what specifically defines its pathogenic nature remains largely undefined. Recent genetic and pharmacological studies in the mouse suggest that the immune modulatory enzyme indoleamine 2,3-dioxygenase (IDO), identified as an important mediator of immune escape in cancer, can also contribute to the development of pathology in the context of chronic inflammatory models of arthritis and allergic airway disease. IDO-deficient mice do not display spontaneous disorders of classical inflammation and small molecule inhibitors of IDO do not elicit generalized inflammatory reactions. Rather, in the context of a classical model of skin cancer that is promoted by chronic inflammation, or in models of inflammation-associated arthritis and allergic airway disease, IDO impairment can alleviate disease severity. Here we offer a survey of preclinical literature suggesting that IDO functions as a modifier of inflammatory states rather than simply as a suppressor of immune function. We propose that IDO induction in a chronically inflamed tissue may shape the inflammatory state to support, or in some cases retard, pathogenesis and disease severity.