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ID PMID Title PublicationDate abstract
24384637 Risk of mycobacterial infections associated with rheumatoid arthritis in Ontario, Canada. 2014 Sep OBJECTIVE: Patients with rheumatoid arthritis (RA) are at increased risk of TB. Little is known about the risk of nontuberculous mycobacteria (NTM) disease in these patients. We sought to ascertain the rate of NTM infection and TB in all residents of Ontario, Canada, with and without RA. METHODS: In a cohort study, all Ontarians aged ≥ 15 years in January 2001 were followed until December 2010. Individuals with RA were identified using a validated algorithm to search hospitalization and physician billing claims. We linked Public Health Ontario Laboratory data to identify all cases of laboratory-confirmed TB and NTM disease. Analysis was performed using Cox proportional hazards regression. RESULTS: We identified 113,558 Ontarians with RA and 9,760,075 Ontarians without RA. Relative to the non-RA group, adjusted hazard ratios (HRs) and 95% CIs for TB (1.92, [1.50-2.47]) and NTM disease (2.07, [1.84-2.32]) demonstrated increased risks in the RA group. Among those with RA, per 100,000 person-years, NTM disease (HR, 41.6; 95% CI, 37.1-46.5) was more common than TB (HR, 8.5; 95% CI, 6.5-10.8). After full adjustment, people with RA who developed NTM disease were 1.81 times as likely to die than uninfected people with RA. CONCLUSIONS: Mycobacterial infections are more common in Ontarians with RA, with NTM disease more likely than TB. NTM disease is associated with an increased risk of death in patients with RA. Given the rising rates of NTM disease worldwide, determining whether this risk is due to the use of immunosuppressive medications vs RA itself is an important objective for future research.
23444285 Pharmacokinetics of modified-release prednisone tablets in healthy subjects and patients w 2013 Mar In rheumatoid arthritis (RA), nocturnal release of proinflammatory cytokines is not adequately counteracted by endogenous glucocorticoid and is associated with symptoms of morning stiffness and pain. Taking exogenous glucocorticoid during the night reduces morning stiffness significantly more than treatment at the conventional time in the morning, although waking to take tablets is unacceptable for patients. Modified-release prednisone tablets were developed to allow administration at bedtime for programmed delivery of glucocorticoid during the night. Single-center crossover studies were conducted, each in ≤24 healthy subjects, to compare the pharmacokinetics of a single 5-mg oral dose of modified-release prednisone and conventional prednisone, as well as the effect of food on bioavailability. There was no substantial difference in pharmacokinetic parameters of the formulations apart from the programmed delay in release of glucocorticoid from the modified-release tablets (C(max) 97%, AUC(0-∞) 101%, 90% confidence intervals within the requisite range for bioequivalence). Administration after a full or light meal did not affect pharmacokinetic characteristics, but bioavailability was reduced under fasted conditions. Pharmacokinetic evaluation in 9 patients with RA confirmed that modified-release prednisone tablets taken at bedtime (around 22:00 h) with or after an evening meal result in programmed release of glucocorticoid 4 to 6 hours after intake.
25381977 The use of an interferon-gamma release assay as a biomarker of response to anti-TNF-alpha 2014 Nov Tumor necrosis factor alpha (TNF-α) is a pleiotropic cytokine that plays a central role in the immune system functioning and in the pathogenesis of rheumatoid arthritis (RA). TNF-α inhibition has been demonstrated effective to treat RA; however, response to anti-TNF-α therapies is heterogeneous, with roughly one-third of patients not achieving disease control. Identification of a biological marker to assess the effectiveness of TNF-α inhibition may help to discriminate patients with a reduced response to anti-TNF-α agents. The aim of this study was to assess whether anti-TNF-α treatment was able to modify the cytokine network interfering with interferon gamma (INFγ) release after phytohemagglutinin (PHA) stimulation of peripheral blood mononuclear cells (PBMCs) from RA patients, according to disease activity. We found that RA patients with active disease had low release of INFγ after PHA stimulation, but anti-TNF-α agents were able to modify INFγ production. In anti-TNF-α responders, we observed a higher release of INFγ, achieving levels comparable with those seen in healthy subjects. The ability of PBMCs from RA patients to release INFγ may serve as a biomarker of disease activity and response to anti-TNF-α. Larger studies are needed to validate these data.
23800448 Long-term safety of abatacept in patients with rheumatoid arthritis. 2013 Oct Abatacept is a selective T cell co-stimulation modulator that was first approved by the Italian Medicines Agency and reimbursed by the Italian National Health Service when used to treat active rheumatoid arthritis "not sufficiently responsive to other disease-modifying anti-rheumatic drugs (DMARDs) including at least one TNF inhibitor", and is now also approved as a first line biological agent. The aim of this review is to summarise the safety data collected in clinical trials and observational studies.
22759910 Adalimumab elicits a restricted anti-idiotypic antibody response in autoimmune patients re 2013 Jan OBJECTIVES: Millions of patients worldwide are treated with therapeutic monoclonal antibodies. These biological therapeutics can be immunogenic, resulting in anti-drug antibody formation which leads to loss of response. Fully human biological agents, such as the anti-tumour necrosis factor α (anti-TNFα) antibody adalimumab, are considered to be weakly immunogenic, but anti-adalimumab antibodies (AAA) were recently detected in more than half of treated patients with rheumatoid arthritis (RA) within 28 weeks of treatment. A study was undertaken to determine the mechanism by which AAA lead to loss of response. METHODS: The specificity of the repertoire of AAA was investigated in a cohort of 50 AAA-positive RA patients. Inhibition experiments using TNFα and patient-derived anti-adalimumab monoclonal antibodies were performed. RESULTS: The antibody response against adalimumab is highly restricted: Fab fragments of a single monoclonal antibody specific for the idiotype of adalimumab inhibited 98.65% (25th-75th percentiles: 98.25-99.90) of the total anti-adalimumab reactivity in serum from 50 AAA-positive patients. The anti-adalimumab response was confined to the TNFα binding region of adalimumab, thereby neutralising its therapeutic efficacy. In line with this restricted specificity, small immune complexes were found in the circulation of AAA-forming patients. CONCLUSIONS: The humoral immune response against adalimumab is highly restricted and limited to the idiotype of the therapeutic antibody. All antibodies result in functional neutralisation of the drug, thereby providing a mechanism by which AAA formation leads to clinical non-response.
23086518 Health care quality indicators on the management of rheumatoid arthritis and osteoarthriti 2013 Feb OBJECTIVE: To make an inventory of quality and content of currently available and published sets of health care quality indicators (HCQIs) for RA and OA. METHODS: A systematic review was performed for documents on the development and/or a description of HCQIs for the management of patients with RA and/or OA, using the PubMed, EMBASE, Web of Science, Cochrane and CINAHL databases up to 1 December 2010 and official websites of arthritis organizations. The following data were extracted: general characteristics, contents and quality of developmental process (six aspects related to the definition of target, target group and stakeholders, patient involvement, description of development and test of validity). RESULTS: The search yielded 498 potentially eligible references and two websites, with ultimately six original HCQI sets for RA and/or OA being identified (one for RA and OA, two for OA and three for RA). The number of HCQI ranged from 7 to 27, with the majority being process indicators. No conflicting indicators between the HCQI sets for one condition were seen. Concerning the quality of the developmental process, all six sets lacked patient involvement. CONCLUSION: Only a limited number of HCQI sets for the management of OA and RA are available, mainly including process indicators. The developmental process was methodologically suboptimal in all cases. As improvement of health care quality is an ongoing process, there is a need for development of HCQIs covering different aspects of health care quality (structure, process and outcome) and using appropriate methodology.
24186846 N-(2-hydroxy phenyl) acetamide produces profound inhibition of c-Fos protein and mRNA expr 2014 Feb Chronic pain and cognitive decline are characteristic symptoms of rheumatoid arthritis. One of the immediate early gene c-fos is overexpressed during peripheral and central noxious conditions and can be used as a marker for neuronal activity/excitability. In the adjuvant-induced arthritis Sprague-Dawley rat model, we examined the dynamics of c-Fos protein and mRNA expression in the amygdala, cortex, hippocampus, and thalamus and evaluated the effects of N-(2-hydroxy phenyl) acetamide (NA-2), a derivative of salicylic acid. The paw volume was assessed as an indicator of peripheral edema and the hyperalgesia associated with arthritis was monitored by gait analysis. The region of interests of the brain from arthritic and non-arthritic animals were used to isolate the RNA and were then reverse transcribed into cDNA. The PCR products were electrophoresed on 1% agarose gel and the gels were visualized in gel-doc system. The frozen brain sections were stained for c-Fos using immunohistochemistry. Negative control experiments were performed without the primary and secondary antibodies to rule out the nonspecific tissue binding of antibodies. We report a significant increase in the c-Fos expression in the arthritic control animals. In comparison to the control group, the treatment of NA-2 treatment was found to block the development of the arthritis-induced c-Fos protein and mRNA expression and peripheral edema. It also significantly reduces the gait deficits which were otherwise observed in the arthritic control group. Both the immunohistochemistry and PCR analysis revealed NA-2 to be more potent in comparison to member of non-steroidal anti-inflammatory drug.
24170559 Efficacy study of multimedia rheumatoid arthritis patient education program. 2014 Jul PURPOSE: The research goal of improving patient adherence was assessed in this randomized controlled trial of the outcomes of a 15-min multimedia educational program when compared to educational literature for rheumatoid arthritis (RA) patients. DATA SOURCES: One hundred eight RA patients from a Midwestern rheumatology outpatient clinic completed the self-reported Medication Adherence Questionnaire (MAQ), the Brief Illness Perception Questionnaire (BIPQ), and Health Assessment Questionnaire (HAQ) at baseline and 1 month after education. A paired samples t-test was use for data analyses to determine if there was a significant difference in the change between the groups at preintervention and 1-month postintervention. CONCLUSIONS: There were no significant differences in the scores between the two groups from pretest to posttest. Results from this study showed that medication adherence, illness perception, and disability were not improved by use of multimedia or the literature within 1 month. IMPLICATIONS FOR PRACTICE: Findings from this research study showed that a short multimedia educational program is as effective as printed materials to educate patients with RA about their disease and treatment. However, neither multimedia nor literature affects medication adherence, illness perception, or disability as self-reported by patients with RA.
23946436 The role of DMARDs in reducing the immunogenicity of TNF inhibitors in chronic inflammator 2014 Feb The management of RA, SpA, psoriasis and inflammatory bowel disease has significantly improved over the last decade with the addition of tumour necrosis factor inhibitors (anti-TNFs) to the therapeutic armamentarium. Immunogenicity in response to monoclonal antibody therapies (anti-drug antibodies) may give rise to low serum drug levels, loss of therapeutic response, poor drug survival and/or adverse events such as infusion reactions. To combat these, the use of concomitant MTX may attenuate the frequency of anti-drug antibodies in RA, SpA and Crohn's disease. Although a similar effect to methotrexate has been observed with AZA usage in the management of Crohn's disease, there is insufficient evidence to suggest that other DMARDs impact immunogenicity. In this article we review the evidence to date on the effect of immunomodulatory therapy when co-administered with anti-TNFs. We also discuss whether such a strategy should be employed in SpA and psoriasis, and if optimization of the MTX dose could improve biologic drug survival and thereby benefit disease management.
23756611 Preoperative predictors for allogenic blood transfusion in hip and knee arthroplasty for r 2013 Sep INTRODUCTION: To identify the preoperative predictors of requirement for postoperative allogenic blood transfusion following hip and knee joint arthroplasty. MATERIALS AND METHODS: We analysed the retrospective data on patients with rheumatoid arthritis who had undergone either total hip or knee arthroplasty at a single university teaching hospital. Factors of age, sex, procedure type, preoperative haemoglobin, blood transfusion data, comorbidities and body mass index were investigated for association with postoperative allogenic blood after hip or knee arthroplasty. RESULTS: Three hundred and forty nine cases of patients with rheumatoid arthritis were reviewed. 21 % (n = 72) required allogenic blood transfusion. The only significant predictive preoperative factors associated with postoperative blood transfusion were a low preoperative haemoglobin (Hb) level (p < 0.001), procedure of total hip arthroplasty (p = 0.008), a previous history of myocardial infarction (p = 0.038) and previous allogenic blood transfusion (p = 0.03). A preoperative haemoglobin <120 g/l was associated with a tenfold increase in transfusion requirement. All patients with a preoperative Hb level <90 g/l were transfused. CONCLUSIONS: The ability to identify those within this high-risk group who are likely to receive blood transfusion allows for an informed, appropriate and cost effective approach to blood management strategies.
23489105 A joint regression analysis for genetic association studies with outcome stratified sample 2013 Jun Genetic association studies in practice often involve multiple traits resulting from a common disease mechanism, and samples for such studies are often stratified based on some trait outcomes. In such situations, statistical methods using only one of these traits may be inadequate and lead to under-powered tests for detecting genetic associations. We propose in this article an estimation and testing procedure for evaluating the shared-association of a genetic marker on the joint distribution of multiple traits of a common disease. Specifically, we assume that the disease mechanism involves both quantitative and qualitative traits, and our samples could be stratified based on the qualitative trait. Through a joint likelihood function, we derive a class of estimators and test statistics for evaluating the shared genetic association on both the quantitative and qualitative traits. Our simulation study shows that the joint likelihood test procedure is potentially more powerful than association tests based on separate traits. Application of our proposed procedure is demonstrated through the rheumatoid arthritis data provided by the Genetic Analysis Workshop 16 (GAW16).
23666827 Necessity of lysophosphatidic acid receptor 1 for development of arthritis. 2013 Aug OBJECTIVE: Lysophosphatidic acid (LPA) is a bioactive lipid that binds to a group of cell surface G protein-coupled receptors (LPA receptors 1-6 [LPA1-6 ]) and has been implicated as an important mediator of angiogenesis, inflammation, and cancer growth. This study was undertaken to analyze the effects of LPA1 on the development of arthritis. METHODS: Expression of LPA receptors on synovial tissue was analyzed by immunohistochemistry and quantitative reverse transcription-polymerase chain reaction. The effects of abrogation of LPA1 on collagen-induced arthritis (CIA) were evaluated using LPA1 -deficient mice or LPA1 antagonist. Migrating fluorescence-labeled CD11b+ splenocytes, which were transferred into the synovium of mice with CIA, were counted. CD4+ naive T cells were incubated under Th1-, Th2-, or Th17-polarizing conditions, and T helper cell differentiation was assessed. Osteoclast formation from bone marrow cells was examined. RESULTS: LPA1 was highly expressed in the synovium of patients with rheumatoid arthritis (RA) compared with that of patients with osteoarthritis. LPA1 -deficient mice did not develop arthritis following immunization with type II collagen (CII). LPA1 antagonist also ameliorated murine CIA. Abrogation of LPA1 was associated with reductions in cell infiltration, bone destruction in the joints, and interleukin-17 production from CII-stimulated splenocytes. Infiltration of transferred CD11b+ macrophages from LPA1 -deficient mice into the synovium was suppressed compared with infiltration of macrophages from wild-type mice. LPA1 antagonist inhibited the infiltration of macrophages from wild-type mice. Differentiation into Th17, but not Th1 or Th2, and osteoclast formation were also suppressed under conditions of LPA1 deficiency or LPA1 inhibition in vitro. CONCLUSION: Collectively, these results indicate that LPA/LPA1 signaling contributes to the development of arthritis via cellular infiltration, Th17 differentiation, and osteoclastogenesis. Thus, LPA1 may be a promising target molecule for RA therapy.
24401632 [Epidemiology of rheumatoid arthritis in middle-aged and elderly population in Luohe City, 2013 Nov 5 OBJECTIVE: To explore the local prevalence of rheumatoid arthritis (RA) among the middle-aged and elderly population. METHODS: A total of 8610 residents were recruited for a two-stage cluster sampling survey through a questionnaire of RA according to 2010 ACR/EULAR classification criteria. Physical examinations and blood tests were performed. RESULTS: The responding rate was 96.10%. Joint score 0, 1, 2, 3, 5 was detected in 13.62%, 7.57%, 2.79%, 1.87% and 0.23% of subjects. The prevalence of joint score 0, 1, 2, 3, 5 was 13.62%, 7.57%, 2.79%, 1.87% and 0.23%. The rate was 17.48% and 14.27% for elevated levels of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), 6.62%, 1.96% and 5.48%, 1.55% for low titer and high titer rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) positive antibody. And 63 RA cases were confirmed. The crude prevalence was 0.76% and 0.71% for standardized prevalence. Compared to males, females had a higher prevalence of RA (1.02% vs 0.39%, P < 0.01). In the population, the awareness rate was 74.60%, cure rate 71.43% and control rate 18.57% respectively. CONCLUSION: The local prevalence of RA in elderly females is higher than that in males. And the treatment and awareness rates are also low.
23451024 Optimising use of electronic health records to describe the presentation of rheumatoid art 2013 BACKGROUND: Research using electronic health records (EHRs) relies heavily on coded clinical data. Due to variation in coding practices, it can be difficult to aggregate the codes for a condition in order to define cases. This paper describes a methodology to develop 'indicator markers' found in patients with early rheumatoid arthritis (RA); these are a broader range of codes which may allow a probabilistic case definition to use in cases where no diagnostic code is yet recorded. METHODS: We examined EHRs of 5,843 patients in the General Practice Research Database, aged ≥ 30 y, with a first coded diagnosis of RA between 2005 and 2008. Lists of indicator markers for RA were developed initially by panels of clinicians drawing up code-lists and then modified based on scrutiny of available data. The prevalence of indicator markers, and their temporal relationship to RA codes, was examined in patients from 3 y before to 14 d after recorded RA diagnosis. FINDINGS: Indicator markers were common throughout EHRs of RA patients, with 83.5% having 2 or more markers. 34% of patients received a disease-specific prescription before RA was coded; 42% had a referral to rheumatology, and 63% had a test for rheumatoid factor. 65% had at least one joint symptom or sign recorded and in 44% this was at least 6-months before recorded RA diagnosis. CONCLUSION: Indicator markers of RA may be valuable for case definition in cases which do not yet have a diagnostic code. The clinical diagnosis of RA is likely to occur some months before it is coded, shown by markers frequently occurring ≥ 6 months before recorded diagnosis. It is difficult to differentiate delay in diagnosis from delay in recording. Information concealed in free text may be required for the accurate identification of patients and to assess the quality of care in general practice.
25311255 Analysis of associations between polymorphisms within genes coding for tumour necrosis fac 2015 Mar INTRODUCTION: Despite the fact that therapy with TNF-α inhibitors constitutes a breakthrough in rheumatoid arthritis management, no improvement is still achieved in approximately 30% of cases. The aim of the study was to evaluate whether single nucleotide polymorphisms (SNPs) within the TNF-α and TNF receptor encoding genes affect the efficacy of therapy with TNF-α inhibitors in patients with RA. METHODS: Five SNPs within the TNF-α and TNF receptor encoding genes (TNFA: G-308A, G-238A, C-857T; TNFR1A G36A; TNFR1B T676G) were determined in 280 RA patients who had been treated with TNF-α inhibitors for at least 6 months or they stop therapy because of adverse events. The association between the relative change in DAS28 and SNP genotypes was tested by linear regression. RESULTS: At week 24, low disease activity or remission was achieved by 45% of the patients. After 6 months remission of the disease or low disease activity were more frequently observed among patients homozygous for the TNFR1A 36A allele than among those who were GG homozygotes (52% vs. 34%, P=0.04). At week 24 DAS28 was significantly lower in the subgroup of patients homozygous for the TNFA-857T variant compared to the C allele carriers (P=0.045). The other polymorphisms were not found to be significantly associated with EULAR response at week 12 and 24 of the anti-TNF treatment. CONCLUSIONS: Homozygosity for the TNFR1A 36A allele and the TNFA-875T variant could act as a genetic factor associated with better response to anti-TNF treatment.
22915617 Association of joint space narrowing with impairment of physical function and work ability 2013 Jul OBJECTIVES: Tumour necrosis factor inhibition plus methotrexate is believed to inhibit radiographic progression independent of inflammation. This analysis assessed whether these protective effects are exerted on bone (joint erosion; JE) and/or cartilage (joint space narrowing; JSN), and what the independent effects of JE/JSN progression are on longer-term patient-reported outcomes. METHODS: PREMIER was a 2-year, randomised, controlled trial of adalimumab plus methotrexate (ADA+MTX) versus the monotherapies. The impact of treatment on the relationships between time-averaged disease activity (TA-DAS28(CRP)) and changes in JE/JSN and associations of JE/JSN with the disability index of the health assessment questionnaire (HAQ-DI) at baseline and weeks 52 and 104 were assessed through non-parametric approaches of analysis of variance and quantile regression. JE/JSN association with employment status was evaluated at baseline and weeks 52 and 104 through logistic regression. RESULTS: Increasing tertiles of TA-DAS28(CRP) were associated with JE and JSN progression in the monotherapy groups, a phenomenon largely absent in ADA+MTX-treated patients. Although JSN was not associated with HAQ-DI at baseline, it was at 52 and 104 weeks. In contrast, JE was not associated with HAQ-DI at any time point examined. Odds of being employed at baseline, 52 weeks and 104 weeks were significantly associated with lower JSN, but not JE, scores. CONCLUSIONS: ADA+MTX inhibited both JE and JSN progression independently of disease activity. JSN played a more prominent role in patient-reported outcomes than JE. Preventing the onset or worsening of JSN probably represents a critical aspect of effective disease management of early rheumatoid arthritis patients.
24824742 A formyl peptide receptor agonist suppresses inflammation and bone damage in arthritis. 2014 Sep BACKGROUND AND PURPOSE: Annexin A1 (AnxA1) is an endogenous anti-inflammatory protein and agonist of the formyl peptide receptor 2 (FPR2). However, the potential for therapeutic FPR ligands to modify immune-mediated disease has been little explored. We investigated the effects of a synthetic FPR agonist on joint disease in the K/BxN model of rheumatoid arthritis (RA) and RA fibroblast-like synoviocytes (FLS). EXPERIMENTAL APPROACH: Arthritis was induced by injection of K/BxN serum at day 0 and 2 in wild-type (WT) or AnxA1(-/-) mice and clinical and histopathological manifestations measured 8-11 days later. WT mice were given the FPR agonist compound 43 (Cpd43) (6 or 30 mg·kg(-1) i.p.) for 4 days. Effects of AnxA1 and Cpd43 on RANKL-induced osteoclastogenesis were assessed in RAW 264.7 cells and human RA FLS and macrophages. KEY RESULTS: Treatment with Cpd43 before or after the onset of arthritis reduced clinical disease severity and attenuated synovial TNF-α and osteoclast-associated gene expression. Deletion of AnxA1 in mice exacerbated arthritis severity in the K/BxN model. In vitro, Cpd43 suppressed osteoclastogenesis and NFAT activity elicited by RANKL, and inhibited IL-6 secretion by mouse macrophages. In human RA joint-derived FLS and monocyte-derived macrophages, Cpd43 treatment inhibited IL-6 release, while blocking FPR2 or silencing AnxA1 increased this release. CONCLUSIONS AND IMPLICATIONS: The FPR agonist Cpd43 reduced osteoclastogenesis and inflammation in a mouse model of RA and exhibited anti-inflammatory effects in relevant human cells. These data suggest that FPR ligands may represent novel therapeutic agents capable of ameliorating inflammation and bone damage in RA.
23508130 Treatment strategies for early rheumatoid arthritis. 2013 May PURPOSE OF REVIEW: Rheumatoid arthritis (RA) is a potentially destructive disease with profound impact on patients' function and quality of life. Newer therapeutic agents have revolutionized outcomes but have not resulted in best outcomes for all patients. In this article, we will review recent progress in the development of strategies to enhance outcomes in patients with early RA (ERA). RECENT FINDINGS: Over the past 10 years, investigators have increasingly focused on additional means for improving long-term prognosis of patients with RA by examining the effect of different strategies to reach clinical targets reflecting optimal levels of disease control. In particular, it has become apparent that patients with ERA have the best chance to reach optimal outcomes, thus normalizing function, and halting radiographic damage. Studies show that strategies including treating to a target, computerizing targets, and combining clinical and biological or imaging targets for patients are enabling more patients to achieve remission, sustained remission, and even drug-free remission. SUMMARY: Overall, the bar has been set higher in clinical research with the expectation that therapeutic approaches for all patients should be implemented to achieve high-level targeted outcomes. Studies evaluating the feasibility of implementing these in practice are needed to achieve this goal for all patients with ERA.
23129430 High frequency of inflammatory back pain and other features of spondyloarthritis in patien 2013 May The aim of this study was to investigate the frequency of patients with rheumatoid arthritis (RA) who have inflammatory back pain (IBP) and meet the existing classification criteria for ankylosing spondylitis (AS) and spondyloarthritis (SpA). We included 167 patients fulfilling the ACR 1987 revised criteria for RA. After obtaining a medical history and performing a physical examination, standard pelvic X-rays for examination of the sacroiliac joints (SIJ) were ordered in all patients. A computed tomography (CT) or magnetic resonance imaging (MRI) of SIJ was performed in patients with suspected radiographic sacroiliitis and MRI of SIJ in those who have IBP but no radiographic sacroiliitis. IBP was defined according to both Calin and experts' criteria. The modified New York (mNY) criteria were used to classify AS, both ESSG and Amor criteria for SpA and ASAS classification criteria for axial SpA. There were 135 female and 32 male patients with a mean age of 54.8 years. The mean disease duration was 9.8 years. RF was positive in 128 patients (79.2 %) and anti-CCP in 120 patients (81.1 %). Twenty-eight patients with RA (16.8 %) had IBP (Calin criteria), and four (2.4 %) had radiographic sacroiliitis of bilateral grade 3. Three patients (1.8 %) fulfilled the mNY criteria for AS, 31 (18.6 %) ESSG and 26 (15.6 %) Amor criteria for SpA. Nine patients (five with MRI sacroiliitis) (5.3 %) were classified as having axial SpA according to new ASAS classification criteria. This study suggests that the prevalence of SpA features in patients with RA may be much higher than expected.
24936783 Toll-like receptors expressed by synovial fibroblasts perpetuate Th1 and th17 cell respons 2014 Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by synovial fibroblast hyperplasia and bone and cartilage erosion. Synovial fibroblast- and T cell-mediated inflammation plays crucial roles in the pathogenesis of RA. However how this inflammation is initiated, propagated, and maintained remains controversial. Here, we systemically examined the contribution of toll-like receptors (TLRs) to the inflammatory mediator production as well as Th1 and Th17 cell hyperactivity in RA. Our results show that rheumatoid arthritis synovial fibroblasts (RASF) express a series of TLRs, including TLR2, TLR3, TLR4, and TLR9, with the predominant expression of TLR3. Moreover, the expression levels of these TLRs were higher than those in osteoarthritis synovial fibroblasts (OASF). Ligation of TLR3, as well as TLR2 and TLR4, resulted in vigorous production of inflammatory cytokines, matrix metalloproteinases (MMPs), and vascular endothelial growth factor (VEGF) in RASF, with activation of the NF-κB, MAPK, and IRF3 pathways. More important, activation of these TLRs expressed by RASF exacerbated inflammatory Th1 and Th17 cell expansion both in cell-cell contact-dependent and inflammatory cytokine-dependent manners, which induced more IFN-γ and IL-17 accumulation. Targeting TLRs may modulate the inflammation in RA and provide new therapeutic strategies for overcoming this persistent disease.