Showing papers by "Shigeki Momohara published in 2010"
TL;DR: The results suggest that CCR6 is critically involved in IL-17–driven autoimmunity in human diseases, and is associated with susceptibility to Graves' and Crohn's diseases.
Abstract: Rheumatoid arthritis is a common autoimmune disease with a complex genetic etiology. Here, through a genome-wide association study of rheumatoid arthritis, we identified a polymorphism in CCR6, the gene encoding chemokine (C-C motif) receptor 6 (a surface marker for Th17 cells) at 6q27, that was associated with rheumatoid arthritis susceptibility and was validated in two independent replication cohorts from Japan (rs3093024, a total of 7,069 individuals with rheumatoid arthritis (cases) and 20,727 controls, overall odds ratio = 1.19, P = 7.7 x 10(-19)). We identified a triallelic dinucleotide polymorphism of CCR6 (CCR6DNP) in strong linkage disequilibrium with rs3093024 that showed effects on gene transcription. The CCR6DNP genotype was correlated with the expression level of CCR6 and was associated with the presence of interleukin-17 (IL-17) in the sera of subjects with rheumatoid arthritis. Moreover, CCR6DNP was associated with susceptibility to Graves' and Crohn's diseases. These results suggest that CCR6 is critically involved in IL-17-driven autoimmunity in human diseases.
272 citations
TL;DR: The mortality of Japanese RA patients is comparable to that in previous reports from western countries, even though the causes of death were significantly different.
Abstract: Objectives: To investigate mortality, cause of death, and risk factors related to mortality in Japanese patients with rheumatoid arthritis (RA).Methods: The IORRA cohort is a large observational cohort established in 2000 at the Institute of Rheumatology, Tokyo Women's Medical University. Essentially, all RA patients were registered and clinical parameters were assessed biannually. For patients who failed to participate in subsequent surveys, simple queries were mailed to confirm survival. Standardized mortality ratios (SMRs) were calculated and mortality risk factors were analysed using a Cox proportional hazard model.Results: We analysed 7926 patients (81.9% females; mean age 56.3 ± 13.1 years; mean disease duration 8.5 ± 8.3 years) with RA who enrolled in IORRA from October 2000 to April 2007. During the observational period (35 443.0 person-years), 289 deaths were reported. Major causes of death included malignancies (24.2%), respiratory involvement (24.2%) including pneumonia (12.1%) and interstitial...
126 citations
TL;DR: It is suggested that the use of TNF blockers is a likely cause of SSI and DVT development in RA patients following major orthopaedic surgery.
Abstract: Objective TNF-alpha blockers reportedly increase the risk of complications in rheumatic patients following surgery. Whereas deep venous thrombosis (DVT) is a significant complication after orthopaedic surgery of the lower limbs, the risk for DVT in RA patients receiving TNF blockers remains unclear. The aim of this study was to identify complications that can be attributed to the use of TNF-alpha blocker therapy. Methods In a retrospective 1:1 pair-matched case-control study, 64 anti-TNF-treated RA surgeries (TNF group) and 64 surgeries treated with conventional DMARDs (DMARDS group) were evaluated for surgical site infection (SSI), DVT and recurrence of arthritis (flare-up). Multivariate logistic regression analysis was performed to test the association of SSI or DVT with the putative risk factors. Results Regression analysis identified the use of TNF blockers as a risk factor for SSI [P = 0.036; odds ratio (OR) = 21.80] and development of DVT (P = 0.03; OR = 2.83) after major orthopaedic surgery: 12.5% (8/64) of the patients in the TNF group had SSI, whereas 2% (1/64) of those in the DMARDs group had SSI. Fifty-one per cent (23/45) of the TNF group, but only 26% (12/45) of the DMARDs group was DVT positive. Flare-ups during the perioperative period were found in 17.2% (11/64) of all patients, and no delay in wound healing occurred in either group. Conclusions These data suggest that the use of TNF blockers is a likely cause of SSI and DVT development in RA patients following major orthopaedic surgery.
122 citations
TL;DR: TNFAIP3, similar to STAT4 and IRF5, may be a common genetic risk factor for SLE and RA that is shared between the Caucasian and Japanese populations.
Abstract: Objective
Genome-wide association (GWA) studies in systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) in Caucasian populations have independently identified risk variants in and near the tumor necrosis factor α (TNFα)–induced protein 3 gene (TNFAIP3), which is crucial for the regulation of TNF-mediated signaling and Toll-like receptor signaling. The aim of this study was to assess the role of TNFAIP3 in the development of SLE and RA in Japanese subjects.
Methods
We selected 2 single-nucleotide polymorphisms (SNPs) from previous GWA studies. Rs2230926 is a nonsynonymous SNP in TNFAIP3 and is associated with SLE, while rs10499194 is an intergenic SNP associated with RA. We then performed 2 independent sets of SLE case–control comparisons (717 patients and 1,362 control subjects) and 3 sets of RA case–control comparisons (3,446 patients and 2,344 control subjects) using Japanese subjects. We genotyped SNPs using TaqMan assays.
Results
We observed a significant association between rs2230926 and an increased risk of SLE and RA in the Japanese population (for SLE, odds ratio [OR] 1.92, 95% confidence interval [95% CI] 1.53–2.41, P = 1.9 × 10−8; for RA, OR 1.35, 95% CI 1.18–1.56, P = 2.6 × 10−5). The intergenic SNP rs10499194 was also associated with SLE and RA, while the risk allele for RA in Caucasians was protective against the diseases in our population.
Conclusion
We demonstrated a significant association between the nonsynonymous variant in TNFAIP3 and the risk for SLE and RA in the Japanese population. TNFAIP3, similar to STAT4 and IRF5, may be a common genetic risk factor for SLE and RA that is shared between the Caucasian and Japanese populations.
85 citations
TL;DR: Several studies from different countries show that the rate of orthopaedic surgery has decreased for patients with rheumatoid arthritis in recent years, and these changes may reflect trends in disease severity, management and health outcomes in each country.
Abstract: Several studies from different countries show that the rate of orthopaedic surgery has decreased for patients with rheumatoid arthritis (RA) in recent years. In Sweden, there was a decrease in RA-related lower limb surgical procedures between 1987 and 2001,1 and in RA-related upper limb surgery between 1998 and 2004.2 Denmark has reported a decrease in the incidence of total hip arthroplasties due to RA,3 and the number of total joint replacement (TJR) operations and synovectomies decreased in the Norwegian population from 1994 to 2004.4 Japan has also reported the declining use of synovectomy surgery for patients with RA.5 These changes may reflect trends in disease severity, management and health outcomes in each country. Meanwhile, Sokka et al reported that the rate of TJR …
65 citations
TL;DR: The incidence of and risk factors for IP in RA patients were determined in a large observational cohort of RA patients in Japan and identified male gender, increased Japanese version of the Health Assessment Questionnaire (J-HAQ) score, decreased pain visual analog scale (VAS), and elevated erythrocyte sedimentation rate as significant risk Factors for MTX-IP, while the only risk factor for RA-IP was male gender.
Abstract: Interstitial lung disease (ILD) is a frequently encountered and sometimes life-threatening complication among patients with rheumatoid arthritis (RA). In this study, we aim to clarify the incidence of and risk factors for ILD using a large observational cohort of RA patients. We analyzed the database from a large observational cohort of Japanese RA patients, the Institute of Rheumatology, Rheumatoid Arthritis (IORRA) cohort. We defined as interstitial pneumonia (IP) computed tomography (CT) pattern of nonspecific interstitial pneumonia or diffuse alveolar damage. Newly developed IP was identified from patient reports over 2.5 years (April 2004 to October 2006) and was confirmed by extensive medical record, chest X-ray radiograph, and CT. The raw and age/gender-adjusted incidence of IP were reported. IP risk factors were analyzed using a nested case-control design was employed using conditional logistic regression analysis with a stepwise method. Thirty-seven patients among 5,699 RA patients were diagnosed with newly developed IP, including 18 cases with methotrexate-induced pneumonitis (MTX-IP) and 15 cases with IP associated with RA (RA-IP). The age-adjusted incidence of MTX-IP among total patients, males, and females was 3.775, 6.667, and 1.013 per 1,000 cases, respectively, and of RA-IP among total patients, males, and females was 1.056, 1.452, and 0.677 per 1,000 cases, respectively. Conditional logistic regression analysis after stepwise variable selection identified male gender, increased Japanese version of the Health Assessment Questionnaire (J-HAQ) score, decreased pain visual analog scale (VAS), and elevated erythrocyte sedimentation rate as significant risk factors for MTX-IP, while the only risk factor for RA-IP was male gender. The incidence of and risk factors for IP in RA patients were determined in a large observational cohort of RA patients in Japan.
61 citations
TL;DR: The present study revealed that the incidence of DVT following TKA was significantly lower in RA patients than in those with OA, and may allow a prophylactic regimen for venous thromboembolism in patients with RA to be reconsidered.
48 citations
TL;DR: In this paper, the association of polymorphisms of TRAF1-C5, a newly identified rheumatoid arthritis (RA) risk locus in Caucasians, with susceptibility to RA and systemic lupus erythematosus (SLE) in Japanese populations was investigated.
Abstract: Objective: The primary aim of this study was to investigate the association of polymorphisms of TRAF1-C5 , a newly identified rheumatoid arthritis (RA) risk locus in Caucasians, with susceptibility to RA and systemic lupus erythematosus (SLE) in Japanese populations. Gene expression levels of TRAF1 and C5 to assess the functional significance of genotypes were also analysed. Methods: A multicentre association study consisting of 4 RA case-control series (4397 cases and 2857 controls) and 3 SLE case-control series (591 cases and 2199 shared controls) was conducted. Genotyping was performed using TaqMan genotyping assay for two single nucleotide polymorphisms (SNPs) that showed the best evidence of association in the previous Caucasian studies. Quantifications of TRAF1 and C5 expression were performed with TaqMan expression assay. Results: Significant differences in allele frequency for both SNPs were observed between RA and control subjects (combined odds ratio = 1.09), while no significant difference was detected between patients with SLE and controls. Interestingly, alleles rs3761847 A and rs10818488 G had increased the risk for RA in the present study, while they decreased the risk in the original studies. A significant difference was found between risk allele carriers and non-carriers of rs10818488 for the expression level of TRAF1 in phorbol myristate acetate-stimulated lymphoblastoid cell lines (p = 0.04). Conclusion: Association of TRAF1-C5 locus with RA susceptibility was detected in the Japanese populations with modest magnitude, while no significant association was observed for SLE. Significant positive effect of genotype on the expression of TRAF1 might support the genetic association between TRAF1 and RA.
42 citations
TL;DR: Geometric features intended to improve knee flexion, including greater antero-posterior stability, a more posterior tibial sulcus, and reshaped femoral condyles, do provide measurable and significant differences in deep-flexion knee kinematics.
29 citations
TL;DR: It is concluded that total knee arthroplasty, which is known to result in good clinical outcomes for damaged knees, has a secondary systemic effect on RA disease activity.
Abstract: Though excellent clinical results have been reported for total knee arthroplasty (TKA) in rheumatoid arthritis (RA) patients, the medium-term effect of TKA on RA disease activity remains unknown. This analysis aimed to assess changes in disease activity after TKA in patients with established RA. We analyzed the systemic effects of TKA on RA disease activity 3 years after intervention. Routine clinical and laboratory assessments were recorded at baseline, less than less than 0.5 years after TKA, and 3 years after TKA. Of the registered RA patients, 130 TKA patients were followed for 3 years after surgery. RA disease activity was measured using the Disease Activity Score 28 (DAS28). Patients were divided into three groups by preoperative baseline DAS28: low (DAS28 ≤ 3.2, n = 8), moderate (DAS28 > 3.2 but ≤5.1, n = 68), and high (DAS28 > 5.1, n = 54) disease activity. The postoperative DAS28 (<0.5 years [DAS1] and 3 years [DAS3] after surgery) scores of each patient were compared to their baseline (DAS0) scores using the paired t-test. The mean DAS28 decreased from 4.85 (DAS0) to 4.14 (DAS1; P = 1.07E-12), and this decrease was sustained at 3 years (DAS3 = 3.97; P = 4.73E-15). Subanalysis results revealed a systemic effect of TKA on disease activity in patients with moderate or high disease activity (DAS0 = 4.33; DAS1 = 3.72 [P = 5.94E-06]; DAS3 = 3.81 [P = 7.89E-06]; and DAS0 = 5.79; DAS1 = 4.86 [P = 1.14E-08]; DAS3 = 4.37 [P = 1.03E-11], respectively). While no significant changes in medication were noted, the average dose of prednisolone tended to decrease over time. We conclude that TKA, which is known to result in good clinical outcomes for damaged knees, has a secondary systemic effect on RA disease activity. Combination therapy consisting of medical treatment and surgical intervention is thought to effectively improve the condition of RA patients who have destructive arthritis in the knee joint, with the effect lasting for at least 3 years.
25 citations
TL;DR: There was a strikingly strong association in SLE patients with nephritis and neuropsychiatric lupus, suggesting that this genetic marker could predict involvement of those severe complications.
Abstract: The objective of this study was to explore the association of single nucleotide polymorphisms (SNPs) of the CD244 gene with several clinical features of systemic lupus erythematosus (SLE). Two hundred and forty-three patients with SLE and 369 healthy controls were enrolled. Two SNPs (rs6682654 and rs3766379) in the CD244 gene were determined by allelic discrimination using a specific TaqMan probe. Only SNP rs3766379 was significantly associated with susceptibility to SLE [P = 0.009; odds ratio (OR) 1.28; 95% confidence interval (CI) 1.04–1.57]. The association was preferentially observed in subsets of SLE patients with nephritis and neuropsychiatric lupus. The frequency of the rs6682654 C allele was strongly associated with nephritis and neuropsychiatric lupus (P = 0.00065; OR 1.99; 95% CI 1.34–2.95, and P = 1.6 × 10−7; OR 3.47; 95% CI 2.12–5.70, respectively), as was the frequency of the rs3766379 T allele (P = 0.0014; OR 1.86; 95% CI 1.27–2.71, and P = 2.6 × 10−7; OR 3.15; 95% CI 2.00–4.96, respectively). In this study, an SNP of the CD244 gene was associated with susceptibility to SLE. There was a strikingly strong association in SLE patients with nephritis and neuropsychiatric lupus, suggesting that this genetic marker could predict involvement of those severe complications.
TL;DR: Outpatient costs for patients with RA increased year after year over the 4-year period under observation in Japan, and medical costs were higher with increasing RA disease activity and disability levels.
Abstract: Our objective was to describe outpatient medical care costs of patients with rheumatoid arthritis (RA) in the prebiologics period in Japan The outpatient costs of 6,771 RA patients (17,666 patient years) who were enrolled in an observational cohort study at the Institute of Rheumatology, Rheumatoid Arthritis (IORRA), in Tokyo, Japan, were calculated from the billing records dated from 2000 to 2004 Associations between outpatient costs and variables such as age, RA duration, RA disease activities, and disability levels were assessed The average outpatient cost gradually increased (+77% in 4 years) from 271,498 JPY per year in 2000 to 292,417 JPY per year in 2004 Medications accounted for approximately 50% of total outpatient costs, which increased 296% during the 4 years The outpatient costs increased in association with aging, longer RA duration, higher Disease Activity Score of 28 Joints (DAS28), and higher Japanese version of Health Assessment Questionnaire (J-HAQ) score Generalized linear regression analysis revealed that both DAS28 and J-HAQ scores were the most significant factors associated with outpatient costs (p < 0001) Outpatient costs for patients with RA increased year after year over the 4-year period under observation in Japan Medical costs were higher with increasing RA disease activity and disability levels
TL;DR: It is concluded that tophaceous gout needs to be included in the differential diagnosis of chronic extensor tenosynovitis of the hand.
Abstract: A 54-year-old woman presented with painless subcutaneous masses on her right hand and spontaneous loss of extension of her ring finger. Surgical exploration of the wrist showed hypertrophic white-colored crystal deposits that both surrounded and invaded into the extensor tendons (intratendinous invasion). Histopathologic examination of the specimen demonstrated findings consistent with gouty tophi. We conclude that tophaceous gout needs to be included in the differential diagnosis of chronic extensor tenosynovitis of the hand.
TL;DR: It is found that TAC is suitable for RA patients who are unable to use biologic agents or to tolerate a high dose of MTX because of their complications or background factors.
Abstract: The objective of this study was to assess the usefulness of tacrolimus (TAC) for rheumatoid arthritis (RA) patients. The first 101 consecutive RA patients in whom TAC treatment was initiated were prospectively registered and their data analyzed. Clinical variables were extracted from the Institute of Rheumatology, Rheumatoid Arthritis (IORRA) database. The 101 patients included 85 females and 16 males. Average doses of TAC were 1.62 mg/day at entry and 2.13 mg/day at month 12. The average doses of concomitantly prescribed prednisolone (6.92 mg/day) and methotrexate (MTX; 8.59 mg/week) were higher than those in all RA patients in the IORRA cohort. At month 12, 57 patients remained on TAC therapy; 18 patients had discontinued TAC due to side effects, and 16 patients had discontinued due to inefficacy. Adverse reactions responsible for discontinuation included gastrointestinal symptoms, renal dysfunction, and infection. According to the European League Against Rheumatism (EULAR) response criteria, 56.5% of the patients who continued TAC at 12 months experienced “good” or “moderate” responses. Through the use of last observation carried forward (LOCF) methodology, the average Disease Activity Score (DAS) 28 significantly improved. We confirmed the usefulness of TAC for the treatment of RA and found that TAC is suitable for RA patients who are unable to use biologic agents or to tolerate a high dose of MTX because of their complications or background factors.
TL;DR: In this paper, a neglected spontaneous rupture of the Achilles tendon in 5 elderly rheumatoid arthritis patients with corticosteroids for a long time was reported, and they did not show any signs, such as click or impact on the rear foot at the moment of the rupture, and had few complaints or obvious symptoms around their ankles or the rear of the foot after the rupture.
Abstract: Spontaneous Achilles tendon rupture associated with rheumatoid arthritis (RA) is a very rare complication. In this report, we have experienced neglected spontaneous rupture of the Achilles tendon in 5 elderly RA patients, and report its clinical features and management. These patients had taken corticosteroids for a long time for RA control. Moreover, they did not show any signs, such as click or impact on the rear foot at the moment of the rupture, and had few complaints or obvious symptoms around their ankles or the rear of the foot after the rupture. This suggests that the lack of severe symptoms prevented the early diagnosis of the Achilles tendon rupture, and that this injury had been neglected during treatment for RA. Therefore, careful diagnosis of the Achilles tendon rupture is needed in elderly patients with RA, even if they have little or no history of trauma.
TL;DR: It is illustrated that when acing an isolated lytic bone lesion in a patient with a myeloproiferative syndrome, in addition to screen for a primary known eoplasm, localized MS transformation could be suspected, even n absence of evocative cell count signs of transformation into eukaemia.
01 Jan 2010
TL;DR: DAS28 were significantly greater in the Irish cohort than in the UK cohort and a higher number of Irish patients achieved a EULAR ‘‘good response’’ (52.3% vs 37.4%, p = 0.03).
Abstract: DAS28 were significantly greater in the Irish cohort (22.04 and 22.44 vs 21.48 and 21.68, respectively, p,0.001). A higher number of Irish patients achieved a EULAR ‘‘good response’’ (52.3% vs 37.4%, p = 0.03). 8