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ID PMID Title PublicationDate abstract
22139828 Predictors of functional impairment and pain in erosive osteoarthritis of the interphalang 2012 May OBJECTIVE: To compare levels of pain and functional limitation in patients with erosive osteoarthritis (OA) of the interphalangeal finger joints with those in patients with nonerosive OA and patients with controlled inflammatory arthritis affecting the hands, and to explore predictors of functional impairment in erosive OA. METHODS: A cross-sectional study including 270 patients with OA of the hands who were referred to rheumatology clinics was performed. A group of patients with inflammatory arthritis (rheumatoid arthritis or psoriatic arthritis) with a low Disease Activity Score in 28 joints (<3.2; n = 79) was examined. Levels of functional impairment (measured by the Functional Index for Hand OA [FIHOA] and Australian/Canadian OA Hand Index [AUSCAN]) and pain were compared between the groups. Predictors of functional impairment in erosive OA were evaluated by generalized linear models. RESULTS: Of 270 patients with hand OA, 167 (61.9%) were classified as having erosive OA. Despite a higher percentage of patients taking analgesics (almost 60%), patients with erosive OA had worse functional outcome and pain scores than patients with controlled inflammatory arthritis or nonerosive OA. Pain scores remained significantly higher in patients with erosive OA after correction for potential confounders. FIHOA and AUSCAN function scores showed a trend toward more disability in patients with erosive OA. Female sex and the number of radiographic affected joints (consisting of joints in the erosive and remodeled radiographic phases) were the strongest predictors of functional impairment in erosive OA. Whether the carpometacarpal joints were affected did not influence functional status in patients with erosive OA. CONCLUSION: Our findings indicate that patients with erosive OA have more functional impairment and significantly more pain compared to patients with controlled inflammatory arthritis affecting the hands. This highlights the significant clinical burden of erosive OA and warrants the search for new treatment strategies.
22622790 IgG4 production against adalimumab during long term treatment of RA patients. 2012 Oct PURPOSE: A substantial part of rheumatoid arthritis (RA) patients is chronically treated with adalimumab. Some of these patients produce antibodies against adalimumab, which correlate with lower serum drug levels and reduced clinical response. Long term exposure to antigens may result in antigen specific IgG4 production as was demonstrated in studies on prolonged exposure to antigens such as different allergens, Factor VIII and IFN-β. Here, we investigate whether long term treatment of RA patients with the therapeutic monoclonal antibody adalimumab leads to the production of specific IgG4 antibodies. METHODS: We developed radio immunoassays to detect total IgG or IgG4 against adalimumab and applied these in a cohort of 271 consecutive RA patients during 3 years of adalimumab treatment. RESULTS: In 32 % of the 271 patients antibodies against adalimumab were detectable. IgG4 antibodies were detected in 29 % of the patients. The proportion IgG4 of total IgG against adalimumab varies widely between patients, and IgG4 was found to contribute significantly to the anti drug antibody (ADA) response in some patients. CONCLUSION: In the immune response against adalimumab in adalimumab-treated RA patients a considerable part of the ADA is IgG4. Although IgG4 is often considered to be harmless due to its lack of effector function, neutralization of adalimumab by IgG4 antibodies will lead to a reduced clinical response.
22170032 Is continuation of anti-tumor necrosis factor-α therapy a safe option for patients who ha 2012 Feb Continuation of anti-tumor necrosis factor-α (TNFα) therapy generally has not been recommended for patients who have developed nontuberculous mycobacterial (NTM) diseases; in daily practice, however, we often encounter patients with refractory rheumatoid arthritis (RA) who experience uncontrollable flares following withdrawal of anti-TNFα agents. Here, we report a case of pulmonary NTM disease caused by Mycobacterium intracellulare occurring in a patient with refractory RA undergoing etanercept therapy. Since there was the concern of an exacerbation of RA symptoms, etanercept was continued during anti-NTM therapy. The patient's pulmonary symptoms and radiological abnormalities were found to have markedly improved in a relatively short time period after beginning the anti-NTM therapy. Additionally, her RA symptoms were adequately controlled without the occurrence of any unexpected adverse events. The continuation of etanercept therapy may be a safe option during anti-NTM therapy if patients' underlying diseases would otherwise be difficult to control. Strictly supervised anti-NTM therapy and patients' informed consent are mandatory. We review the medical literature on NTM disease associated with anti-TNFα therapy for rheumatic diseases and discuss the safety of simultaneous use of anti-TNFα agents in patients during anti-NTM therapy.
21385358 The tumour-associated glycoprotein podoplanin is expressed in fibroblast-like synoviocytes 2011 Mar 7 INTRODUCTION: Activated fibroblast-like synoviocytes (FLSs) in rheumatoid arthritis (RA) share many characteristics with tumour cells and are key mediators of synovial tissue transformation and joint destruction. The glycoprotein podoplanin is upregulated in the invasive front of several human cancers and has been associated with epithelial-mesenchymal transition, increased cell migration and tissue invasion. The aim of this study was to investigate whether podoplanin is expressed in areas of synovial transformation in RA and especially in promigratory RA-FLS. METHODS: Podoplanin expression in human synovial tissue from 18 RA patients and nine osteoarthritis (OA) patients was assessed by immunohistochemistry and confirmed by Western blot analysis. The expression was related to markers of synoviocytes and myofibroblasts detected by using confocal immunofluoresence microscopy. Expression of podoplanin, with or without the addition of proinflammatory cytokines and growth factors, in primary human FLS was evaluated by using flow cytometry. RESULTS: Podoplanin was highly expressed in cadherin-11-positive cells throughout the synovial lining layer in RA. The expression was most pronounced in areas with lining layer hyperplasia and high matrix metalloproteinase 9 expression, where it coincided with upregulation of α-smooth muscle actin (α-sma). The synovium in OA was predominantly podoplanin-negative. Podoplanin was expressed in 50% of cultured primary FLSs, and the expression was increased by interleukin 1β, tumour necrosis factor α and transforming growth factor β receptor 1. CONCLUSIONS: Here we show that podoplanin is highly expressed in FLSs of the invading synovial tissue in RA. The concomitant upregulation of α-sma and podoplanin in a subpopulation of FLSs indicates a myofibroblast phenotype. Proinflammatory mediators increased the podoplanin expression in cultured RA-FLS. We conclude that podoplanin might be involved in the synovial tissue transformation and increased migratory potential of activated FLSs in RA.
22460414 Mechanisms of muscle wasting in sarcopenia. 2012 Mar Approximately 66% of the patients with rheumatoid arthritis (RA) have significant loss of cell mass (rheumatoid cachexia), mainly of skeletal muscle (rheumatoid sarcopenia). Sarcopenia is defined as muscle wasting associated with functional impairment. Patients with RA possess significant reduction in muscle strength, caused by muscle protein wasting, and loss of functionality. Various conditions leading to muscle wasting involve different pathways of intracellular signaling that trigger: (i) programmed cell death (apoptosis); (ii) increased protein degradation through autophagy, calcium-dependent proteases (calpains and caspases), and proteasome system; (iii) decreased satellite cell activation, responsible for muscle regeneration. This article aimed at reviewing these general mechanisms of sarcopenia and their involvement in RA. Greater knowledge of these mechanisms may lead to the development of innovative therapies to this important comorbidity.
21467710 Adalimumab-induced interstitial pneumonia with an improvement of pre-existing rheumatoid a 2011 A 78-year-old man with an 18-year history of rheumatoid arthritis (RA) was treated with tumor necrosis factor (TNF)-α inhibitor adalimumab. Chest computed tomography showed a previously detected consolidation. The patient's arthritic symptoms substantially decreased with the initiation of adalimumab, with a simultaneous improvement of the lung lesion. However, additional interstitial pneumonia was found a month after starting adalimumab. This course suggested that adalimumab might be effective against RA-associated lung disease, but may also have caused drug-induced interstitial pneumonia. This is the first report indicating that TNF-α inhibitor shows simultaneously conflicting actions in a patient with RA-related lung disease.
22024200 Bone mineral density by digital X-ray radiogrammetry is strongly decreased and associated 2011 Oct 24 BACKGROUND: The aims were to explore bone mineral density (BMD) by digital X-ray radiogrammetry (DXR) in postmenopausal women with long-lasting rheumatoid arthritis (RA) in relation to dual x-ray absorptiometry (DXA)-BMD, joint destruction by conventional radiographs and disease related variables in a cross-sectional study. METHODS: Seventy-five postmenopausal women with RA were examined by DXA measuring DXA-BMD of the forearm, total hip and lumbar spine, by scoring joint destruction on plain radiographs by the method of Larsen and by DXR-BMD in metacarpals two to four. The DXR-BMD results of the RA women were compared with an age and sex-matched reference database. A function of DXR-BMD in relation to age and disease duration was created. Associations were investigated by bivariate and multiple linear regression analyses. RESULTS: DXR-BMD was strongly decreased in RA patients compared to the reference database (p < 0.001). Calculations showed that DXR-BMD was not markedly influenced the first years after diagnosis of RA, but between approximately 5-10 years of disease there was a steep decline in DXR-BMD which subsequently levelled off. In multiple regression analyses disease duration, CRP and DXR-BMD were independent variables associated with Larsen score (R2= 0.64). Larsen score and BMD forearm were independent determinants of DXR-BMD (R2 = 0.79). CONCLUSIONS: DXR-BMD was strongly reduced and associated with both Larsen score and DXA-BMD forearm in these postmenopausal women with RA implying that DXR-BMD is a technique that reflects both the erosive process and bone loss adjacent to affected joints.
22382341 Efficacy and safety of CE-224,535, an antagonist of P2X7 receptor, in treatment of patient 2012 Apr OBJECTIVE: To evaluate efficacy and safety of CE-224,535, a selective P2X(7) receptor antagonist, versus placebo, in patients with active rheumatoid arthritis (RA) and inadequate response to methotrexate (MTX). METHODS: In our phase IIA study (ClinicalTrials.gov no. NCT00628095; A6341009), patients aged ≥ 18 years with active RA were randomized to receive either CE-224,535 (500 mg bid) or placebo for 12 weeks; all patients continued a stable background dose of ≥ 7.5 mg MTX. RESULTS: The American College of Rheumatology 20% (ACR20) response rate (primary efficacy endpoint) was not significantly different from placebo for CE-224,535 (34.0% vs 36.2%; p = 0.591) at Week 12, or at any timepoint over the 12-week treatment period. There was no significant difference at Week 12 for the ACR20 response rate following subgroup analyses by age, sex, baseline disease activity, baseline duration of disease, geographic region, or concomitant use of steroids. ACR50/ACR70 response rates and change from baseline in Disease Activity Score 28-joint C-reactive protein (DAS28-3-CRP) and Health Assessment Questionnaire-Disability Index for CE-224,535 were not significant at Week 12 versus placebo. Treatment-emergent adverse events (AE) were reported by 62.3% (CE-224,535) and 55.3% (placebo) of patients; the most common AE were nausea (11.3%, CE-224,535; 4.3%, placebo) and diarrhea (7.5%, CE-224,535; 4.3%, placebo). The proportion of patients discontinuing due to an AE was 9.4% (CE-224,535) and 6.4% (placebo); no deaths were reported. Serious AE occurred in 3.8% (CE-224,535) and 2.1% (placebo) of patients; none was considered treatment-related. CONCLUSION: CE-224,535 was not efficacious, compared with placebo, for the treatment of RA in patients with an inadequate response to MTX. CE-224,535 demonstrated an acceptable safety and tolerability profile.
22207481 Radiological features and therapeutic responses of pulmonary nontuberculous mycobacterial 2012 Sep OBJECTIVE: This study was performed to evaluate the radiological features of and therapeutic responses to pulmonary disease caused by nontuberculous mycobacteria (NTM) in the setting of biological therapy for rheumatoid arthritis (RA). METHODS: We conducted a retrospective chart review of 13 patients from multiple centers who had developed pulmonary NTM disease during biological therapy for RA, including infliximab, etanercept, adalimumab, and tocilizumab. RESULTS: Most cases were asymptomatic or resulted in only common-cold-like symptoms. Abnormalities in computed tomography (CT) imaging were protean and frequently overlapped. The most predominant pattern was nodular/bronchiectatic disease (six cases), followed by alveolar infiltrate (three cases), cavitary disease (two cases), and pulmonary nodules (two cases). In most cases, pulmonary NTM disease had spread from a preexisting lesion; in particular, bronchial/bronchiolar abnormalities. In three cases, one or more nodular lesions with or without calcification were a focus of disease. Following the discontinuation of biological agents, most patients responded to anti-NTM therapy. Two patients showed no exacerbation in the absence of any anti-NTM therapy. In one patient, restarting tocilizumab therapy while continuing to receive adequate anti-NTM therapy produced a favorable outcome. In two other patients with a previous history of pulmonary NTM disease, introducing biological therapy led to recurrence, but anti-NTM therapy was effective in these patients. CONCLUSION: CT abnormalities of pulmonary NTM disease in RA patients receiving biological therapy were variable, but were not unique to this clinical setting. NTM disease can spread from preexisting structural abnormalities, even if they are minute. Contrary to our expectations, the therapeutic outcomes of pulmonary NTM disease were favorable in these patients.
21885510 Damage and progression on radiographs in individual joints: data from pivotal randomized c 2011 Sep OBJECTIVE: Radiographic progression is usually assessed by Sharp-based methods (van der Heijde-modified Sharp score and the Genant-modified Sharp score). The aim of this study was to evaluate, in a range of randomized controlled trials (RCT), the presence of erosions and joint space narrowing (JSN) in all individual joints, as well as progression in these joints, and to determine if any redundancy exists due to infrequently involved joints. METHODS: Four databases of rheumatoid arthritis RCT that were all scored according to van der Heijde's modification of the Sharp score were included in a descriptive analysis. RESULTS: Irrespective of different readers, different patient populations, and different disease durations per trial, similar patterns emerged. Both erosions and JSN occurred in all sites. Erosions occurred most frequently in the feet, preferentially in 5th metatarsophalangeal joint (MTP-5). JSN occurred most frequently in the wrist. Change from baseline in erosions and JSN followed the pattern of involvement at baseline, so that MTP-5, and to a lesser extent MTP-3 and MTP-4, preferentially showed progression in erosive damage. Joints in the wrist showed highest tendency to worsen over time with respect to JSN. CONCLUSION: These data indicate that both erosions and JSN must be assessed for damage, and that a more abbreviated joint count cannot be used for radiographic scoring.
23196313 Assessment of use of complementary alternative medicine and its impact on quality of life 2011 Feb PURPOSE: Complementary and alternative medicine (CAM) has witnessed an increase in use in recent times in rheumatological conditions and is expected to have impact on the quality of life (QOL). We had planned to conduct this study to investigate the extent of use of CAM and its effect on QOL of patients at a tertiary care center. MATERIALS AND METHODS: Ethics committee approval was obtained. Sixty patients suffering from osteoarthritis (OA) and rheumatoid arthritis (RA) were enrolled as per the selection criteria, after obtaining their informed consent. Each patient was interviewed for CAM use/non-use, and Western Ontario and McMaster Universities (WOMAC) (modified) index for QOL was recorded by the study personnel. STATISTICAL ANALYSIS: The normality was checked by using Kolmogorov-Smirnov test. Descriptive statistics was performed and Mann-Whitney U-test was used to compare the QOL of CAM users and non-users. RESULTS: Of the 60 patients enrolled with OA (10) and RA (50), 58% (35/60) used CAM. Ayurveda and massage therapy were the commonest [80% (28/35)], followed by yoga asana [34% (12/35)] and homoeopathy [20% (7/35)]. It was observed that combinations of therapies were used too. Nearly half [49% (17/35)] of the CAM users were on self-prescribed medication and 71% (25/35) of them did not inform the physician of CAM use. The QOL of CAM users (WOMAC score: 56.31 ± 6.82) was better than that of CAM non-users (WOMAC score: 60.16 ± 4.02) (P value 0.01). CONCLUSION: Patients with RA frequently used CAM and QOL improvised with CAM use. We observed that self-administration of CAM was common and this was not informed to the treating physician.
21821865 Sustained disease remission and inhibition of radiographic progression in methotrexate-nai 2011 Nov OBJECTIVE: To assess the efficacy and safety of abatacept plus methotrexate versus methotrexate alone in early erosive rheumatoid arthritis (RA). METHODS: The AGREE was a 2-year phase IIIb multinational study in early (≤ 2 years) RA. During the double-blind period (year 1), patients were randomly assigned 1:1 to receive abatacept+methotrexate or methotrexate alone; all patients received open-label abatacept+methotrexate during year 2. Clinical outcomes assessed included 28-joint disease activity score (DAS28) defined remission, low disease activity score (LDAS), American College of Rheumatology (ACR) responses and physical function. Radiographic outcomes were assessed using the Genant-modified Sharp total score (TS). Safety was monitored throughout. RESULTS: Of the 459 patients completing year 1, 433 patients (94.3%) completed year 2. DAS28-defined remission, LDAS, ACR and physical function were sustained through year 2 in the original abatacept+methotrexate group, with 55.2% in remission at 2 years. Upon introduction of abatacept in the methotrexate-alone group, additional patients achieved DAS28-defined remission (44.5% vs 26.9%), LDAS (60.4% vs 43.2%) and improved ACR 70 (49.8% vs 31.7%) for year 2 versus year 1. Less radiographic progression was observed at 2 years in the original abatacept+methotrexate group than the methotrexate-alone group (change in TS 0.84 vs 1.75, p<0.001). No new safety issues were seen. Similar rates of serious adverse events, serious infections and autoimmune events were observed in years 1 and 2. CONCLUSIONS: The AGREE trial was the first to examine the impact of T-cell co-stimulation modulation with abatacept in patients with early erosive RA. Early treatment with abatacept+methotrexate resulted in greater sustainable clinical, functional and radiographic benefits than methotrexate alone, with acceptable safety and tolerability. TRIAL REGISTRATION: NCT00122382.
22975733 Therapeutic efficacy of tocilizumab in patients with rheumatoid arthritis refractory to an 2013 Jul OBJECTIVE: Tocilizumab (TCZ) is effective in patients with rheumatoid arthritis (RA) who are refractory to anti-tumor-necrosis-factor (anti-TNF) biologics. The Rheumatoid Arthritis Society Disease Activity Score in 28 Joints (DAS28) is used to evaluate the response to TCZ. However, DAS28 is inappropriate marker because TCZ normalizes C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) in the early stage of treatment. The aim of our study was to test the usefulness of magnetic resonance imaging (MRI)-based markers of response to TCZ treatment. METHODS: Nine patients with RA who were refractory to anti-TNF inhibitors (six to infliximab, one to etanercept, one to adalimumab, and one to both) were assessed. MRI images of both hands were obtained by low-field extremity MRI at baseline, 20, and 44 weeks of treatment, in addition to assessment with DAS28-ESR. The effect of TCZ on RA was examined by compact MRI score (cMRIS). RESULTS: All patients showed good or moderate response to TCZ treatment, as evaluated by significant reduction in DAS28-ESR at both 20 and 44 weeks (p < 0.001, each, relative to baseline). In contrast, MRI-based indexes (e.g., cMRIS, synovitis, edema, erosion scores) improved significantly at 44 weeks but not at 20 weeks. CONCLUSION: Differences in response to TCZ therapy were determined based on the method of evaluation, suggesting that MRI-based markers are potentially useful for evaluating RA response to TCZ therapy.
22377704 MTHFR C677T, MTHFR A1298C, and OPG A163G polymorphisms in Mexican patients with rheumatoid 2012 MTHFR polymorphisms C677T and A1298C are associated with reduced MTHFR enzyme activity and hyperhomocysteinemia, which has been associated with osteoporosis. The A163G polymorphism in osteoprotegerin (OPG) has been studied in osteoporosis with controversial results. The objective of the present study was to investigate the association(s) among MTHFR C677T, MTHFR A1298C, and OPG A163G polymorphisms in Mexican patients with rheumatoid arthritis and osteoporosis. The femoral neck and lumbar spine bone mineral densities (BMDs) were measured in 71 RA patients, and genotyping for the three polymorphisms was performed via restriction fragment length polymorphism analysis. Patients with osteoporosis/osteopenia exhibited statistically significant differences in the genotype frequencies of MTHFR C677T as well as an association with femoral neck BMD; TT homozygotes had lower BMDs than patients with the CT genotype, and both of these groups had lower BMDs than patients with the CC genotype. The associations of the MTHFR C677T polymorphism with osteoporosis/osteopenia and femoral neck BMD suggest that these polymorphisms confer a risk of developing osteoporosis in patients with rheumatoid arthritis, a risk that may be reduced with folate and B complex supplementation.
22209972 1858 C/T polymorphism of the protein tyrosine phosphatase nonreceptor 22 gene and rheumato 2011 Nov BACKGROUND AND AIMS: A single nucleotide polymorphism (SNP) of the protein tyrosine phosphatase nonreceptor gene (PTPN22) confers susceptibility to rheumatoid arthritis (RA) and certain other classical autoimmune diseases. The association between PTPN22 1858C/T polymorphism and the risk of RA is still controversial and ambiguous; therefore, we performed this meta-analysis to confirm some relationships. METHODS: We conducted a search in the PubMed database without a language limitation, covering all papers published until June 20, 2011. Overall, 19 case-control studies with 11,727 cases and 12,640 controls were retrieved based on the search criteria for RA susceptibility related to the 1858C/T polymorphism. Odds ratios (OR) and 95% confidence intervals (CI) were used to assess the strength of this association. Publication bias was assessed with Eggers test. RESULTS: We found that PTPN22 1858C/T polymorphism could increase RA risk in overall genetic models in Europeans (T-allele vs. C-allele, OR = 1.54, 95% CI = 1.47-1.62, P(heterogeneity) = 0.143; TT vs. CC, OR = 2.86, 95% CI = 2.29-3.57, P(heterogeneity) = 0.302; TC vs. CC, OR = 1.45, 95% CI = 1.38-1.53, P(heterogeneity) = 0.273; TT + TC vs. CC, OR = 1.49, 95% CI = 1.42-1.56, P(heterogeneity) = 0.208; TT vs. TC + CC, OR = 2.52, 95% CI = 1.95-3.25, P(heterogeneity) = 0.296). Furthermore, significant relationships were detected among PTPN22 1858C/T polymorphism and RF(+) or RF(-) RA risk. No obvious evidence of publication bias was detected in the overall analysis. CONCLUSIONS: Our study indicated that PTPN22 1858T allele was significantly associated with increased RA risk.
22930199 Pulmonary inflammation in mice with collagen-induced arthritis is conditioned by complete 2012 Dec Following immunization with collagen II (CII) in complete Freund's adjuvant (CFA), DBA/1 mice develop arthritis of major joints. This collagen-induced arthritis (CIA) is used as a model for rheumatoid arthritis (RA) in man. Inflammatory changes in lung tissue commonly occur in RA. However, evidence for pulmonary inflammation in CIA is scarce and ambiguous. Here, we demonstrate pulmonary inflammation accompanying CIA in wild-type DBA/1 mice. In IFN-γ receptor-deficient (IFN-γR KO) mice, inflammation was more frequent and more severe. Injection of CFA only (without CII) proved to be as efficient in eliciting pulmonary inflammation as immunization with CFA + CII, though being less effective in causing arthritis. Significant correlation in severity between joint and pulmonary involvement could not be demonstrated. Macroscopic, microscopic, and functional characteristics of pulmonary inflammation in the mice resembled those seen in human RA. Increased inflammation in IFN-γR KO mice was accompanied by augmented expression of various cytokines and chemokines, as measured by RT-PCR on affected tissue. Treatment with a TNF-α inhibitor ameliorated lung pathology. We conclude that CIA in DBA/1 mice is accompanied by pulmonary inflammation. Although both disease processes are kept in check by endogenous IFN-γ, lack of strict parallelism indicates that overlap in their pathogeneses is partial.
21438869 Expression of CD64 on polymorphonuclear neutrophils in patients with familial Mediterranea 2011 Jun Familial Mediterranean fever (FMF) is an autoinflammatory disease characterized by recurrent episodes of fever and serosal or synovial inflammation. We examined the utility of CD64 (FcγRI) expression in polymorphonuclear neutrophils (PMNs) as clinical and biological parameters in patients with FMF. We studied 12 Japanese FMF patients (mean age; 22·8 ± 15·5 years, male/female: 2/10), along with rheumatoid arthritis patients (RA, n = 38 male/female: 6/32, mean age; 52·2 ± 15·3 years), systemic lupus erythematosus (SLE, n = 15 male/female: 0/15, mean age; 38·5 ± 15·9 years) and 12 healthy subjects (male/female: 3/9, mean age; 37·9 ± 17·2 years). CD64 expression on PMNs was determined using flow cytometry. The quantitative expression of CD64 in patients with FMF (2439·6 ± 2215·8 molecules per PMN) was significantly higher than in healthy subjects (547·8 ± 229·5, P = 0·003) or in patients with RA (606·5 ± 228·2, P < 0·0001) and SLE (681·3 ± 281·1, P = 0·004). The increased CD64 expression on PMNs isolated from untreated FMF patients was down-regulated by colchicine treatment. NACHT-LRR-PYD-containing protein 3 (NLRP3) activation using MurNAc-L-Ala-D-isoGln (MDP) resulted in increased CD64 expression on PMNs from healthy subjects. Our results suggest that quantitative measurement of CD64 expression on PMNs can be a valuable tool to discriminate between FMF and autoimmune diseases.
22262390 Posterior cruciate ligament-retaining total knee arthroplasty in patients with rheumatoid 2011 Nov 16 7We previously reported the minimum eight-year follow-up results of cruciate-retaining total knee arthroplasty in a consecutive series of seventy-two knees in patients with rheumatoid arthritis. In the present study, we evaluated the longer-term outcomes after twenty to twenty-five years of follow-up. Since the publication of our original study, ten knees have been revised: three because of periprosthetic fracture, three because of infection, two because of patellofemoral failure, and two because of posterior instability. The rate of implant survival at twenty years after surgery was 69% (95% confidence interval [CI], 56% to 79%) with revision for any reason as the end point, 81% (95% CI, 69% to 89%) with femoral or tibial component revision for any reason as the end point, and 93% (95% CI, 83% to 97%) with posterior instability as the end point. These long-term results demonstrate that posterior cruciate ligament insufficiency with instability was rarely the cause of failure following cruciate-retaining total knee arthroplasty in patients with rheumatoid arthritis.
22878601 Serum levels of matrix metalloproteinase (MMP) 9, a risk factor for acute coronary syndrom 2012 Matrix metalloproteinase 9 (MMP-9) is a risk factor for cardiovascular events. The serum MMP-9 levels were measured before and 2 weeks after treatment with infliximab (3 mg/kg) in 12 rheumatoid arthritis (RA) patients. The serum average MMP-9 level was 238.5 ng/ml before treatment with infliximab in RA patients (normal range: less than 43.8 ng/ml). Infliximab reduced the serum average MMP-9 level significantly (161.66 ng/ml, P = 0.0425). The serum MMP-9 level was high in the RA patients with active disease, and it was reduced by infliximab independently of the reduction in disease activity. Thus, infliximab may reduce the risk of cardiovascular events directly.
22416254 Role of p21-activated kinase 1 in regulating the migration and invasion of fibroblast-like 2012 Jul OBJECTIVE: To investigate the role of p21-activated kinase 1 (PAK1) in regulating migration, invasion and MMP expression in RA fibroblast-like synoviocytes (FLS). METHODS: RA FLS migration and invasion in vitro were measured by the Boyden chamber method. Invasion of RA FLS into cartilage was detected in the severe combined immunodeficiency (SCID) mouse co-implantation model of RA in vivo. PAK1 and MT1-MMP expression were examined by western blotting. ELISA was used to measure the production and activity of MMPs. RESULTS: Phosphorylated PAK1 (p-PAK1) protein expression was increased in ex vivo synovial membrane cells from RA patients. Stimulation with IL-1β or TNF-α up-regulated p-PAK1 expression. Inhibition of PAK1 by transfection with dominant negative PAK1 mutant (dnPAK1) reduced in vitro migration and invasion of RA FLS. In the SCID mouse model, RA FLS invasion into cartilage was attenuated by transfection with dnPAK1 in vivo. PAK1 regulated IL-1β-induced production and activity of MMP-13 and MT1-MMP. Inhibition of MMP-13 or MT1-MMP activity also reduced RA FLS invasion. Furthermore, dnPAK1 transfection inhibited c-Jun N-terminal kinase (JNK) activation, but did not affect the activities of extracellular signal-regulated kinases and p38. Inhibition of the JNK activity by chemical inhibitor significantly reduced the migration, invasion and production of MMP-13 and MT1-MMP. CONCLUSION: PAK1 plays an important role in regulating the migration, invasion and production and activity of MMPs in RA FLS, which is mediated by the JNK pathway. This suggests a novel strategy targeting PAK1 to prevent joint destruction of RA.