Showing papers by "Shigeki Momohara published in 2008"
TL;DR: It is known that synovial tissue andsynovial fluid from RA patients contain increased concentrations of several chemokines, such as monocyte chemoattractant protein‐4 (MCP‐4)/CCL13, pulmonary and activation‐regulated chemokine (PARC)/ CCL18, monokine induced by interferon‐γ (Mig)/CXCL9, stromal cell‐derived factor 1 (SDF‐1)/C
Abstract: Rheumatoid arthritis (RA) is a chronic symmetric polyarticular joint disease that primarily affects the small joints of the hands and feet. The inflammatory process is characterized by infiltration of inflammatory cells into the joints, leading to proliferation of synoviocytes and destruction of cartilage and bone. In RA synovial tissue, the infiltrating cells such as macrophages, T cells, B cells and dendritic cells play important role in the pathogenesis of RA. Migration of leukocytes into the synovium is a regulated multi-step process, involving interactions between leukocytes and endothelial cells, cellular adhesion molecules, as well as chemokines and chemokine receptors. Chemokines are small, chemoattractant cytokines which play key roles in the accumulation of inflammatory cells at the site of inflammation. It is known that synovial tissue and synovial fluid from RA patients contain increased concentrations of several chemokines, such as monocyte chemoattractant protein-4 (MCP-4)/CCL13, pulmonary and activation-regulated chemokine (PARC)/CCL18, monokine induced by interferon-gamma (Mig)/CXCL9, stromal cell-derived factor 1 (SDF-1)/CXCL12, monocyte chemotactic protein 1 (MCP-1)/CCL2, macrophage inflammatory protein 1alpha (MIP-1alpha)/CCL3, and Fractalkine/CXC3CL1. Therefore, chemokines and chemokine-receptors are considered to be important molecules in RA pathology.
241 citations
TL;DR: It is concluded that STAT4 is associated with rheumatoid arthritis and systemic lupus erythematosus in the Japanese, and is a common genetic risk factor for autoimmune diseases, with similar strength across major racial groups.
Abstract: Objective
STAT4 encodes a transcriptional factor that transmits signals induced by several key cytokines, and it might be a key molecule in the development of autoimmune diseases. Recently, a STAT4 haplotype was reported to be associated with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) in Caucasian populations. This was replicated in a Korean RA population. Interestingly, the degree of risk of RA susceptibility with the STAT4 haplotype was similar in the Caucasian and Korean populations. The present study was undertaken to investigate the effect of STAT4 on susceptibility to RA and SLE in the Japanese.
Methods
We performed an association study using 3 independent Japanese RA case–control populations (total 3,567 cases and 2,199 controls) and 3 independent Japanese SLE populations (total 591 cases). All samples were genotyped using the TaqMan fluorogenic 5′ nuclease assay for single-nucleotide polymorphism (SNP) rs7574865, which tags the susceptibility haplotype. The association of the SNP with disease susceptibility in each case–control study was calculated using Fisher's exact test, and the results were combined, using the Mantel-Haenszel method, to obtain combined odds ratios (ORs).
Results
We observed a significant association of the STAT4 polymorphism with susceptibility to both RA and SLE. The combined ORs for RA and SLE, respectively, were 1.27 (P = 8.4 × 10−9) and 1.61 (P = 2.1 × 10−11) for allele frequency distribution; these ORs were quite similar to those previously observed in the Caucasian population.
Conclusion
We conclude that STAT4 is associated with RA and SLE in the Japanese. Our results indicate that STAT4 is a common genetic risk factor for autoimmune diseases, with similar strength across major racial groups.
158 citations
TL;DR: TNF-alpha activates AhR expression in RA synovial tissue, and that cigarette smoking and exposure to TCDD enhances RA inflammatory processes, thus TCDd exposure, such as smoking exacerbates RA pathophysiology.
Abstract: Objective. Environmental factors are involved in RA pathogenesis and epidemiological studies have suggested that smoking is an environmental risk factor for RA. The 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is one of the major toxic components in cigarettes. To clarify the biological effects of smoking in RA, we investigated the role of TCDD in RA pathogenesis. Methods. Human synovial tissue was obtained from RA and OA patients and aryl hydrocarbon receptor (AhR) expression in these tissues was evaluated using immunohistochemistry and real-time PCR. Expression of various cytokines was measured by real-time PCR following stimulation of RA synoviocytes with different concentrations of TCDD. To study the role of AhR, we treated RA synoviocytes with � -naphthoflavone, a known AhR antagonist. To evaluate which signal transduction pathways were stimulated by the TCDD–AhR interaction, we used inhibitors of nuclear factor-� B (NF-� B) and extra-cellular stimulus-activated kinase (ERK). Results. Higher AhR mRNA and protein levels were observed in RA synovial tissue than in OA tissue. TCDD up-regulated the expression of IL-1� , IL-6 and IL-8 through binding to AhR, and this effect was transmitted via the NF-� B and ERK signalling cascades. AhR expression in synovial cells was up-regulated by TNF-� . Conclusion. TNF-� activates AhR expression in RA synovial tissue, and that cigarette smoking and exposure to TCDD enhances RA inflammatory processes. TCDD induces inflammatory cytokines via its association with AhR, resulting in stimulation of the NF-� B and ERK signalling cascades. Thus TCDD exposure, such as smoking exacerbates RA pathophysiology.
127 citations
Journal Article•
TL;DR: The data suggested that the SAA-RAGE-stimulated NF-kappaB signaling pathway has an important role in the pathogenesis of RA.
Abstract: OBJECTIVE: Rheumatoid arthritis (RA) is a chronic, symmetric polyarticular joint disease and serum amyloid A (SAA) is an acute-phase protein that is upregulated during the course of RA. We investigated the role of SAA in the pathogenesis of RA. METHODS: Fibroblast-like synovial cells (FLS) were established from RA joints. SAA-stimulated expression of cytokines from FLS was evaluated by ELISA. Nuclear factor-kappaB (NF-kappaB) activation by SAA was evaluated by luciferase assay. NF-kappaB activation and IkappaBalpha degradation were evaluated by Western blotting and nuclear localization of p65 subunit of NF-kappaB in FLS. Expression of receptor for advanced glycation end-products (RAGE) in synovial tissue was evaluated by immunohistochemical study. Effects of preincubation of soluble RAGE on NF-kappaB activation by SAA was evaluated by Western blotting of IkappaBalpha. RESULTS: SAA stimulated the transcriptional activation by NF-kappaB in a dose-dependent manner and induced expression of the proinflammatory cytokines interleukin 6 (IL-6) and IL-8. Higher expression of RAGE in synovial tissue from patients with RA was noted. SAA induced IkappaBalpha degradation, with the peak effect around 30 minutes. Preincubation of SAA with soluble recombinant RAGE protein prevented SAA-induced IkappaBalpha degradation. SAA stimulation promoted nuclear translocation of NF-kappaB, whereas preincubation of SAA with RAGE inhibited nuclear translocation. CONCLUSION: Our data suggested that the SAA-RAGE-stimulated NF-kappaB signaling pathway has an important role in the pathogenesis of RA.
60 citations
TL;DR: Environmental factors, including infectious agents, smoking, sex hormones, pregnancy etc, have been extensively studied previously and understanding of how these factors contribute to the development of RA may lead to the better understanding of pathogenesis.
Abstract: Rheumatoid arthritis (RA) is a systemic, chronic inflammatory disease that affects 0.5-1% of the population. RA causes progressive joint destruction that leads to the restriction of activities of daily living and deterioration of quality of life. Although the pathogenesis of RA has not yet been fully elucidated, it is considered to be a complex, multifarious disease that is influenced by both genetic and environmental factors. Genetic influences that contribute to RA susceptibility have been demonstrated both in studies of twins and families, as well as in genome-wide linkage scans, and it is estimated that genetic factors are responsible for 50-60% of the risk of developing RA. Thus, environmental factors may explain the remaining risk of developing RA. A large variety of environmental factors such as infectious agents, smoking, sex hormones, pregnancy etc. have been extensively studied previously. Understanding of how these factors contribute to the development of RA may lead to the better understanding of pathogenesis of RA.
45 citations
TL;DR: The aim of the present study was to determine whether this FcγRIIIA V/F polymorphism is associated with treatment outcome of infliximab (the first TNF-α inhibitor approved in Japan) in Japanese patients with RA.
Abstract: The prediction of treatment outcome of patients with rheumatoid arthritis (RA) may avoid wasting time and cost of treatment, and allow better targeting of aggressive treatment. Recently, an amino acid-changing polymorphism in the gene encoding the Fcγ IIIA receptor (FcγRIIIA), valine (V)/phenylalanine (F) (rs396991), was found to be associated with increased likelihood of response to tumour necrosis factor (TNF)-α inhibitors in the treatment of RA.1 The aim of the present study was to determine whether this FcγRIIIA V/F polymorphism is associated with treatment outcome of infliximab (the first TNF-α inhibitor approved in Japan) in Japanese patients with RA.
The study was approved by the Tokyo Women’s Medical University Genome Ethics Committee. The …
25 citations
TL;DR: It is concluded that MMP-3 functional polymorphism is associated with serum M MP-3 titre, but is not a direct predictor for outcome measures in Japanese RA patients.
Abstract: Objective. A bi-allelic polymorphism on the promoter region, � 1612 ins/del A, was found to influence the production of MMP-3. Since MMP-3 plays a particularly pivotal role in joint destruction, the MMP-3 gene is thought to be an interesting target gene of disease severity in RA. We attempt to determine whether the MMP-3 promoter polymorphism is associated with serum titre of MMP-3, disease activity and severity in Japanese RA patients. Methods. DNA samples were obtained from 1504 RA patients as part of the Institute of Rheumatology Rheumatoid Arthritis observational cohort study. From the 2006 spring data, serum MMP-3 levels of 820 patients were available by enzyme immunoassay. Joint damage score at 5-yr disease duration could be measured using the Sharp/van der Heijde method in 162 patients. Genotyping of � 1612 ins/del A was performed using fluorescent-labelled fragment analysis. Differences in serum MMP-3 level and joint damage score among genotypes of � 1612 ins/del A polymorphism were analysed by linear regression analysis. Results. No significant differences were found among MMP-3 genotypes on patient characteristics including disease activity score (P ¼ 0.51) or health assessment questionnaire (P ¼ 0.99). A significant effect of risk allele on serum MMP-3 level was observed (P ¼ 0.038), while no significant effect was observed on radiographic joint damage (P ¼ 0.47). Conclusion. We conclude that MMP-3 functional polymorphism is associated with serum MMP-3 titre, but is not a direct predictor for outcome measures in Japanese RA patients.
23 citations
TL;DR: It is recommended that bursa excision be considered even in cases of iliopsoas bursitis associated with mild femoral neuropathy when destructive changes in the hip joint are also present, and a 63-year-old woman with a six-year history of rheumatoid arthritis is presented.
Abstract: We present the case of a 63-year-old woman with a six-year history of rheumatoid arthritis (RA) and a left iliopsoas bursitis. Radiography had detected destructive changes in her hip joint associated with her bursitis, and she had reported some paresthesia along the left anterior distal thigh. Her pain and numbness remained tolerable, and her disease activity was well controlled until she accidentally fell on the floor, which resulted in an unstable intertrochanteric fracture of left femur with displacement of the proximal portion. The fracture was successfully treated with open reduction and internal fixation, but after the surgery, her femoral nerve palsy worsened. She subsequently underwent bursa excision after the failure of conservative treatment. Accordingly, after bursa excision, the postoperative course was uneventful, and her neurological symptoms gradually disappeared. We would recommend that bursa excision be considered even in cases of iliopsoas bursitis associated with mild femoral neuropathy when destructive changes in the hip joint are also present.
17 citations
TL;DR: The relationships between serum concentrations of SAA and other markers of RA, such as erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and matrix metalloproteinase-3 (MMP-3), and disease activity of RA are investigated.
12 citations
TL;DR: The case of total knee arthroplasty (TKA) inducing treatment success with infliximab in a RA patient after an inflIXimab secondary response failure is encountered, suggesting it is possible that synovectomy can effectively be combined with inflixedimab treatment in RA patients with decreased inflixIMab efficacy or in primary nonresponders.
Abstract: Dear Editor, We have read with interest the article by Kanbe and Inoue [1] concerning the treatment of synovectomy combining with infliximab for rheumatoid arthritis (RA). We encountered the case of total knee arthroplasty (TKA) inducing treatment success with infliximab in a RA patient after an infliximab secondary response failure. The present case was a 45-year-old Japanese woman who was diagnosed with RA at 38 years of age. She was treated for 2 years with methotrexate (MTX) and prednisolone (PSL) after taking other disease-modifying antirheumatic drugs. However, the disease activity remained high in spite of those medications. The patient presented to our hospital, and infliximab (3 mg/kg) was added to PSL and MTX at weeks 0, 2, and 6, followed by administration every 8 weeks. She initially had a significant decrease in disease activity, fulfilling the moderate response criteria by the European League Against Rheumatism grading system. However, the effect gradually decreased, and in particular, the right knee joint was markedly swollen and tender. Therefore, the dose of MTX was increased to 17.5 mg with the same dose of infliximab (3 mg/kg) because increasing the dose of infliximab above 3 mg/kg is not approved by the Japanese Ministry of Health, Labor and Welfare. Nevertheless, she felt more pain in her right knee joint, and after almost 3 years on infliximab, she underwent TKA after the 21st infliximab infusion. Laboratory findings showed erythrocyte sedimentation rate (ESR) 89 mm/h, C-reactive protein (CRP) 5.75 mg/dl, and Disease Activity Score in 28 joints (DAS28) 4.33 just before the operation. These data were dramatically improved after surgery: ESR=13 mm/h, CRP=0.08 mg/dl, and DAS28=2.82 at 32 weeks post operation. Thereafter, infliximab was administered for 1 year at the same dose and interval without relapse of the high disease activity. Most swollen and tender joints became asymptomatic. The blockade of tumor necrosis factor (TNF) has had a significant impact on the therapy for RA after the impressive clinical and radiological benefits observed in clinical trials. Despite the success of these therapies, a significant proportion of patients treated with infliximab fail to respond [2]. In particular, Buch et al. reported that about half of patients treated with infliximab demonstrate secondary nonresponse in the first year [3]. To overcome these response failures, several studies have sought to address the value of dose escalation of infliximab. Both the ATTRACT [2] and ASPIRE [4] studies suggest that additional efficacy can be gained from higher dosage, increased frequency of infusions [5], or switching to other TNF-alpha antagonists [6, 7]. Otherwise, the inflamed synovium in RA produces many cytokines and chemokines, which promote joint cartilage destruction, and it was thought likely that surgically removing the synovium and lavaging the joint would reduce the total amount of cytokines and chemokines. Therefore, it is possible that synovectomy can effectively be combined with infliximab treatment in RA patients with decreased infliximab efficacy or in primary nonresponders [1]. In TKA, excision of the synovial tissue is usually performed, and the pathological articular cartilage is replaced with the components. The right knee joint in this case was the primary inflamed joint after failing to respond Clin Rheumatol (2008) 27:549–550 DOI 10.1007/s10067-008-0858-4
9 citations
TL;DR: Assessment of the risk factors for wrist surgery in a cohort of rheumatoid arthritis patients recruited and followed prospectively for 6 years provided important insights into the course of the disease and its impact on patients, as well as the potential consequences for health care resource utilization planning.
Abstract: To assess the risk factors for wrist surgery in a cohort of rheumatoid arthritis (RA) patients recruited and followed prospectively for 6 years. A linked registry study was performed using information from a large observational cohort of RA patients followed at the Institute of Rheumatology, Tokyo Women’s Medical University. Baseline routine clinical and laboratory assessments were recorded. The data were analyzed using the multivariate Cox regression model that included variables such as gender, age, disease duration, a visual analog scale (VAS) generated by physicians, a patient-reported VAS for pain (VAS-pain), a VAS for general health, disability level using the Japanese version of the Health Assessment Questionnaire (J-HAQ), erythrocyte sedimentation rate, and serum levels of C-reactive protein and rheumatoid factor as potential risk factors. Of the 5,497 patients registered at baseline, 122 (2.22%) had surgery on one or both wrist joints. Multivariate Cox regression analysis of the variables revealed positive coefficients for J-HAQ and VAS-pain and that advanced age and long RA duration were associated with a reduced risk of wrist surgery. The hazard ratios were: 1.515 for J-HAQ, 1.126 for VAS-pain, 0.985 for age, and 0.964 for RA duration. Advanced age and long RA duration were associated with a decreased risk of wrist surgery, while J-HAQ and VAS-pain were associated with an increased risk. The identification of the risk factors for wrist surgery provides important insights into the course of the disease and its impact on patients, as well as the potential consequences for health care resource utilization planning.
TL;DR: The results indicate that TD is basically maintained during the course of CR-TKA in RA, but may be slightly affected by factors other than the PCL itself.
Abstract: Controversy persists concerning around posterior cruciate ligament (PCL) retention in total knee arthroplasty (TKA) for patients with rheumatoid arthritis (RA). This study investigated factors affecting anteroposterior (AP) instability following cruciate-retaining (CR)-TKA. In a consecutive series of 70 knees from 52 RA patients, total displacement (TD) was measured using a KT-2000 arthrometer before and after CR-TKA under anesthesia, and changes in TD were defined as ΔTD. TD was also measured under anesthesia in 65 knees from 48 RA patients at a mean of 7.5 years after CR-TKA. Mean postoperative TD was 9.4±0.95 mm, representing an increase of about 1.5–1.8 mm compared to preoperative TD, and possibly reflecting resection of the anterior cruciate ligament. Correlation analysis revealed significant negative correlations between ΔTD and both preoperative flexion angle ( r =−0.67, p r =−0.63, p r =0.61, p
Journal Article•
TL;DR: To the Editor: The authors read with interest the article by Baraliakos, et al concerning no increase in incidence of infusion reactions after infliximab readministration in patients with ankylosing spondylitis with interest.
Abstract: To the Editor:
We read with interest the article by Baraliakos, et al concerning no increase in incidence of infusion reactions after infliximab readministration in patients with ankylosing spondylitis1. In some rheumatoid arthritis (RA) cases, this treatment has to be discontinued due to infusion reactions2. Overall, the incidence of infusion reaction to infliximab is about 5% of cases in Crohn’s disease (CD)3,4, and as recently reported, when combined with glucocorticoid therapy, from 4.6% to 8.6% in RA5. Further, delayed infusion reactions in CD were reported in 25% of patients who received infliximab again after a 2–4 year interval without…