Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
ID | PMID | Title | PublicationDate | abstract |
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22684398 | Analysis of perioperative clinical features and complications after orthopaedic surgery in | 2013 May | OBJECTIVE: To evaluate perioperative changes in rheumatoid arthritis (RA) patients treated with tocilizumab. METHODS: We collected RA cases with tocilizumab and orthopaedic surgery from 1999 to 2010. Incidences of postoperative infections, delayed wound healing, and RA symptom flare-ups were extracted from the data for comparison with patients without these postoperative events. We also evaluated the changes in C-reactive protein (CRP) and body temperature in patients without postoperative complications with normal CRP before surgery, i.e., patients without postoperative events in whom the tocilizumab level was maintained, for each duration to discontinuation before surgery. RESULTS: A total of 161 cases (n = 122) were collected. The patients had mean age of 56.9 years, and mean disease duration of 12.8 years at operation. Joint replacement surgery was performed in 89 cases. Three patients had postoperative infections (two superficial and one organ/space surgical-site infection), 20 had delayed wound healing, and 36 had RA symptom flare-ups. Delayed wound healing occurred most commonly in patients who underwent spinal surgery (P = 0.0061, versus patients without delayed wound healing). CRP levels were high when tocilizumab was restarted in patients with RA symptom flare-ups (P = 0.0010, versus patients without RA symptom flare-ups). Increased postoperative CRP was observed in patients without postoperative events when the duration from final tocilizumab infusion to surgery was long. The changes in body temperature showed a similar trend to CRP. CONCLUSIONS: Although it has been demonstrated that infection rates in patients treated with tocilizumab are by no means high, incidence of delayed wound healing was significantly higher in cases with surgical interventions such as foot and spinal surgeries. Many patients treated with tocilizumab remained in a normal range of CRP even during the perioperative period. For prevention of perioperative complications, observation of postoperative conditions and surgical wounds, and subjective symptoms of patients are considered important. | |
22457743 | Validation study of existing gene expression signatures for anti-TNF treatment in patients | 2012 | So far, there are no means of identifying rheumatoid arthritis (RA) patients who will fail to respond to tumour necrosis factor blocking agents (anti-TNF), prior to treatment. We set out to validate eight previously reported gene expression signatures predicting therapy outcome. Genome-wide expression profiling using Affymetrix GeneChip Exon 1.0 ST arrays was performed on RNA isolated from whole blood of 42 RA patients starting treatment with infliximab or adalimumab. Clinical response according to EULAR criteria was determined at week 14 of therapy. Genes that have been reported to be associated with anti-TNF treatment were extracted from our dataset. K-means partition clustering was performed to assess the predictive value of the gene-sets. We performed a hypothesis-driven analysis of the dataset using eight existing gene sets predictive of anti-TNF treatment outcome. The set that performed best reached a sensitivity of 71% and a specificity of 61%, for classifying the patients in the current study. We successfully validated one of eight previously reported predictive expression profile. This replicated expression signature is a good starting point for developing a prediction model for anti-TNF treatment outcome that can be used in a daily clinical setting. Our results confirm that gene expression profiling prior to treatment is a useful tool to predict anti-TNF (non) response. | |
22447331 | Tacrolimus treatment increases bone formation in patients with rheumatoid arthritis. | 2013 Aug | Tacrolimus is a calcineurin inhibitor, and it is used for the treatment of rheumatoid arthritis (RA). It works by inhibiting nuclear factor of activated T cells and inducting immunosuppression. This study aims to evaluate the influence of tacrolimus on the bone metabolism of patients with RA. Twenty-eight RA patients in three centers received tacrolimus 3 mg once daily for 24 weeks. Blood samples for evaluating bone metabolism and cytokines were collected at Weeks 0 and 24. We measured the serum C-telopeptide of type I collagen (sCTx-I), osteocalcin and inflammatory cytokines. We analyzed the data using the Kruskal-Wallis test and Spearman's correlation. IL-2 and IL-6 were significantly decreased after the administration of tacrolimus (p = 0.027 and p = 0.024). There was no significant difference in the serum level of sCTx-I before and after treatment. The level of serum osteocalcin at Week 24 was significantly increased compared to the level at Week 0 (p = 0.002). The increase of osteocalcin was correlated with the reductions of IL-2 and IFN-γ (r = 0.405, p = 0.033 and r = 0.380, p = 0.046, respectively). Tacrolimus treatment increased bone formation markers in RA patients. This suggests that tacrolimus may play a role to inhibit bone erosion by increasing bone formation as well as improving the clinical symptoms of RA. | |
20838947 | An observational study of patient-rated outcome after atlantoaxial fusion in patients with | 2011 Mar | BACKGROUND: Fusion is used to address several types of abnormality of the atlantoaxial segment. Traditionally, outcome has been assessed by achieving solid bony union. Recently, however, patient-rated outcome instruments have been increasingly used, although these may be influenced by concomitant comorbidity. QUESTIONS/PURPOSES: We therefore asked whether patients with rheumatoid arthritis (RA), with its associated comorbidity, had worse self-rated outcomes after C1-2 fusion than patients with osteoarthritis (OA). PATIENTS AND METHODS: We retrospectively reviewed all 30 (23 OA and seven RA) prospectively followed patients in our local Spine Registry (part of the Spine Society of Europe Spine Tango Registry) who had undergone C1-2 fusion. Before surgery and 3 and 12Â months later, patients completed the multidimensional Core Outcome Measures Index (COMI) questionnaire. Global outcome and satisfaction with treatment were also assessed. RESULTS: We found no group differences for duration of operation, blood loss, or perioperative surgical or general complications. Compared with the OA group, the RA group showed a better baseline COMI score and less improvement in the COMI from preoperatively to 12Â months followup. However, the proportion of "good" global scores at 12Â months followup was similarly high in both groups (87% OA and 86% RA) as was satisfaction (96% for OA versus 86% for RA). CONCLUSIONS: Symptoms and impairment were less severe in the RA group at baseline and showed less improvement after surgery, but the proportion of "good global outcomes" was similar in both groups, and the great majority of patients in both groups were satisfied with their treatment. LEVEL OF EVIDENCE: Level III, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence. | |
21719420 | Multi-examiner reliability of automated radio frequency-based ultrasound measurements of c | 2011 Oct | OBJECTIVES: To assess the reliability of the automated radio frequency (RF)-based US measurement of carotid intima-media thickness (IMT) performed by rheumatologists and to evaluate the variability between this method and the conventional B-mode US measurement of carotid IMT in RA patients. METHODS: Twelve rheumatologists measured in two blinded rounds the IMT of both common carotid arteries (CCAs) of seven RA patients with an automated RF-based method. At each round, a cardiologist measured both CCA-IMTs of the patients using an automated B-mode method. Inter-observer reliability for RF-based IMT measurements was evaluated by the intra-class correlation coefficient (ICC). Intra-observer reliability for RF-based IMT measurements was assessed using the root mean square coefficient of variation (RMS-CV), Bland-Altman method and ICC. Agreement between the two US methods was evaluated by the Bland-Altman method, ICC and RMS-CV. RESULTS: Inter-observer ICCs for the RF-based CCA-IMT measurements were 0.85 (95% CI 0.69, 0.94) for the first round, and 0.77 (95% CI 0.55, 0.91) for the second round. RMS-CVs for the RF-based CCA-IMT measurements varied from 5.6 to 11.7%. The mean intra-observer ICC for the RF-based CCA-IMT measurements was 0.61 (95% CI 0.46, 0.71). In the Bland-Altman analysis for agreement between RF-based and B-mode CCA-IMT measurements, the mean difference varied from -0.6 to -19.7 μm. Inter-method ICCs varied from 0.57 to 0.83 for 11 rheumatologists. Inter-method RMS-CVs varied from 11.3 to 13.7%. CONCLUSIONS: Our results suggest that automated RF-based CCA-IMT measurement performed by rheumatologists can be a reliable method for assessing cardiovascular risk in RA patients. | |
21593065 | Failures of the RM finger prosthesis joint replacement system. | 2011 Sep | In our unit a high failure rate of the RM finger prosthesis joint replacement system was noted, prompting a review of cases. A series of patients underwent implantation under the care of one surgeon and the results were monitored. Twenty-one devices were implanted of which 16 were inserted for rheumatoid disease. Patients were reviewed regularly and the implant performance was assessed critically along with survival of the implant to revision, infection or death of the patient. The mean follow-up was 32 months. Unacceptable failure rates at early and medium term stages were identified, with 15 of the implants revised by 2 years. Loosening was the commonest mode of failure. The authors do not recommend the use of this implant, especially in cases of rheumatoid arthritis. | |
21884589 | The association between systemic glucocorticoid therapy and the risk of infection in patie | 2011 Aug 31 | INTRODUCTION: Infection is a major cause of morbidity and mortality in patients with rheumatoid arthritis (RA). The objective of this study was to perform a systematic review and meta-analysis of the effect of glucocorticoid (GC) therapy on the risk of infection in patients with RA. METHODS: A systematic review was conducted by using MEDLINE, EMBASE, CINAHL, and the Cochrane Central Register of Controlled Trials database to January 2010 to identify studies among populations of patients with RA that reported a comparison of infection incidence between patients treated with GC therapy and patients not exposed to GC therapy. RESULTS: In total, 21 randomised controlled trials (RCTs) and 42 observational studies were included. In the RCTs, GC therapy was not associated with a risk of infection (relative risk (RR), 0.97 (95% CI, 0.69, 1.36)). Small numbers of events in the RCTs meant that a clinically important increased or decreased risk could not be ruled out. The observational studies generated a RR of 1.67 (1.49, 1.87), although significant heterogeneity was present. The increased risk (and heterogeneity) persisted when analyses were stratified by varying definitions of exposure, outcome, and adjustment for confounders. A positive dose-response effect was seen. CONCLUSIONS: Whereas observational studies suggested an increased risk of infection with GC therapy, RCTs suggested no increased risk. Inconsistent reporting of safety outcomes in the RCTs, as well as marked heterogeneity, probable residual confounding, and publication bias in the observational studies, limits the opportunity for a definitive conclusion. Clinicians should remain vigilant for infection in patients with RA treated with GC therapy. | |
22426579 | Limited end-user knowledge of methotrexate despite patient education: an assessment of rhe | 2012 Apr | BACKGROUND: Methotrexate (MTX) is a first-line disease-modifying agent and anchor drug for biologic therapy used in rheumatoid arthritis and other inflammatory rheumatic disorders. Adverse effects are a common cause of drug discontinuation and include preventable serious incidents that may result in patient harm or death. OBJECTIVES: The objective of this study was to audit adherence by health professionals to national and international guidelines for patient education and risk reduction in patients prescribed MTX for inflammatory rheumatic diseases. METHODS: A combination of interviews, case record reviews, and self-administered patient knowledge questionnaires with individual patient feedback was used. The setting was the rheumatology outpatient department of a district general hospital. RESULTS: Fifty-one patients participated in the audit. The mean age was 58.6 (SD, 13.1) years and median duration of disease was 3.7 years (interquartile range, 1.7-7.6 years). Nurse-led patient education was documented at baseline for 94.1% of participants. Despite this, only 11.8% of participants recognized the potentially lethal drug-drug interaction with trimethoprim/Septrin (co-trimoxazole), and less than 60.8% recognized possible major adverse effects related to MTX. Although lifestyle implications relating to alcohol consumption and pregnancy/breast-feeding were recognized by the majority, only 52.9% of males were aware of recommendations in relation to conception. Univariable and multivariable analyses identified male sex, not speaking English as a first language, and a longer duration of therapy as predictors of lower levels of patient knowledge. CONCLUSIONS: Despite consistent baseline patient education, end-user knowledge and awareness pertinent to MTX safety are limited. Good-quality written information in the most appropriate language, patient feedback on educational programs, follow-up testing of patient knowledge, and targeted reeducation are recommended to address individual deficiencies in core knowledge. | |
22709525 | RANKL synthesized by articular chondrocytes contributes to juxta-articular bone loss in ch | 2012 Jun 18 | INTRODUCTION: The receptor activator nuclear factor-kappaB ligand (RANKL) diffuses from articular cartilage to subchondral bone. However, the role of chondrocyte-synthesized RANKL in rheumatoid arthritis-associated juxta-articular bone loss has not yet been explored. This study aimed to determine whether RANKL produced by chondrocytes induces osteoclastogenesis and juxta-articular bone loss associated with chronic arthritis. METHODS: Chronic antigen-induced arthritis (AIA) was induced in New Zealand (NZ) rabbits. Osteoarthritis (OA) and control groups were simultaneously studied. Dual X-ray absorptiometry of subchondral knee bone was performed before sacrifice. Histological analysis and protein expression of RANKL and osteoprotegerin (OPG) were evaluated in joint tissues. Co-cultures of human OA articular chondrocytes with peripheral blood mononuclear cells (PBMCs) from healthy donors were stimulated with macrophage-colony stimulating factor (M-CSF) and prostaglandin E2 (PGE2), then further stained with tartrate-resistant acid phosphatase. RESULTS: Subchondral bone loss was confirmed in AIA rabbits when compared with controls. The expression of RANKL, OPG and RANKL/OPG ratio in cartilage were increased in AIA compared to control animals, although this pattern was not seen in synovium. Furthermore, RANKL expression and RANKL/OPG ratio were inversely related to subchondral bone mineral density. RANKL expression was observed throughout all cartilage zones of rabbits and was specially increased in the calcified cartilage of AIA animals. Co-cultures demonstrated that PGE2-stimulated human chondrocytes, which produce RANKL, also induce osteoclasts differentiation from PBMCs. CONCLUSIONS: Chondrocyte-synthesized RANKL may contribute to the development of juxta-articular osteoporosis associated with chronic arthritis, by enhancing osteoclastogenesis. These results point out a new mechanism of bone loss in patients with rheumatoid arthritis. | |
22646866 | Effect of very early treatment in rheumatoid arthritis on bone oedema and synovitis, using | 2012 Oct | OBJECTIVE: To evaluate the magnetic resonance imaging (MRI) findings of hand involvement before and 1 year after treatment in patients with early rheumatoid arthritis (RA). METHOD: MRI of the dominant hand was performed in 22 patients fulfilling the new criteria for early RA. The patients were divided into three groups. Nine had very early RA (VERA; disease duration < 3 months), seven had early RA (ERA; disease duration < 6 months), and six had established RA (ESTRA; disease duration > 12 months). The MRI protocol consisted of fat-suppressed T2, and plain and contrast-enhanced T1-weighted sequences. Assessment of bone marrow oedema, synovitis, and bone erosions was performed by the OMERACT RA MRI scoring system. Patients were treated with methotrexate (MTX) 0.2 mg/kg/body weight/week and prednisone 7.5 mg/day. Clinical assessment was evaluated using the Disease Activity Score for 28 joint indices (DAS28). RESULTS: After treatment, a significant decrease was observed: (a) in DAS28 of VERA (6.2 ± 0.9 vs. 2.4 ± 1.2), ERA (5.3 ± 0.8 vs. 2.8 ± 1.0), and ESTRA patients (5.7 ± 8.0 vs. 2.7 ± 0.7; p < 0.05); (b) in bone oedema (16.77 ± 13.78 vs. 5.88 ± 6.31) and synovitis (12.44 ± 6.44 vs. 2.88 ± 3.25) of VERA patients; and (c) in synovitis (7.57 ± 6.32 vs. 1.42 ± 1.81) of ERA patients (p < 0.05). No significant difference was found in erosions in any group. CONCLUSION: Bone marrow oedema and synovitis decrease significantly when RA is diagnosed and treated early. MRI is useful in the early detection of these changes. MTX treatment resulted in a significant decrease in DAS28 score and significant improvement in bone oedema and synovitis. | |
21185876 | Serum salusin-alpha level in rheumatoid arthritis. | 2011 Feb 25 | Rheumatoid arthritis (RA), a chronic inflammatory disease, leads to early and accelerated atherosclerosis; however, its pathogenesis is not yet fully documented. Salusin-α and β are novel bioactive peptides. Salusin-α suppresses macrophage foam cell formation, while salusin-β stimulates. Moreover, decreased serum salusin-α level has been reported previously in patients with coronary artery disease. The aims of the study were to assess serum salusin-α level and its association with predictors of atherosclerosis in a cohort of patients with RA. The study included 56 RA patients, 37 Behcet's disease (BD) patients, and 29 healthy controls (HC). TNF-α, IL-6 and salusin-α levels, homeostasis model assessment (HOMA-IR) index and common carotid intima-media thickness (IMT) were determined. In the RA and BD groups, salusin-α levels (p<0.001 and p<0.01, respectively) and IMTs (p<0.001 for both) were higher compared to the HC group. However, the level of salusin-α was not directly associated with the IMT in all the groups. Serum salusin-α levels are increased in RA and BD, although they have increased IMT. Salusin-α has been reported to have anti-atherogenic effects in previous studies. However, it seems that salusin-α does not directly affect the atherogenesis in RA and BD. Further studies are needed to understand the regulation of salusin-α and determination of its relations with the predictors of atherosclerosis in RA and BD. | |
21889242 | Dynamic impression insole in rheumatoid foot with metatarsal pain. | 2012 Feb | BACKGROUND: Custom molded insoles with metatarsal supports are used to redistribute excessive loading under the metatarsal heads in patients with metatarsalgia. However, these pressure reductions are usually insufficient for the rheumatoid foot with painful deformed metatarsal heads. We developed an effective insole made by sequential foam padding under successive walking impression. METHODS: Seventeen consecutive rheumatoid arthritic outpatients with metatarsal pain participated in this repeated measures study of 7-mm flat Ethylene Vinyl Acetate, custom molded and dynamic impression insoles. Peak plantar pressure, pressure-time integral, contact area and mean force were measured by a Pedar-X mobile system. Pain levels were assessed using a Visual Analog Scale (0-10). FINDINGS: Compared to the Ethylene Vinyl Acetate control, the metatarsal head peak pressure and pressure-time integral were significantly reduced in dynamic impression insoles by 46.3% (P<0.001) and 48.9% (P<0.001), respectively. Compared to the custom molded insole, the dynamic impression insole significantly reduced 18.3% of peak pressure (P<0.001) and 20.1% of pressure-time integral (P<0.001) by increasing 8.1% of contact area (P=0.005) at the metatarsal heads, but there were no significant differences in all variables at the heel. After using the dynamic impression insole, the mean pain score was significantly reduced from 7.6 to 1.1 (P<0.001), and six participants experienced total pain-relief in walking. INTERPRETATION: Dynamic impression insoles effectively relieve metatarsal pain because of a larger weight-bearing area. Forefoot shape during walking should be taken into consideration in orthotic designs for maximum pressure reduction. Consequently, we recommend using materials with memory properties to dynamically accommodate painful metatarsal heads. | |
21236658 | Intra-articular corticosteroid injections: a critical literature review with up-to-date fi | 2011 Jun | Intra-articular corticosteroid injections are frequently used in the management of both osteoarthritis and rheumatoid arthritis, with most evidence and articles confined to the knee joint. There are few articles that deal with intra-articular corticosteroid injections in the foot and ankle. The aim of this critical literature review is to find the most up-to-date material on intra-articular corticosteroid injections for the foot and ankle. This article will review: effects of corticosteroids; pharmacology of injectable corticosteroids; mechanism of action; indications and contraindications; agents and the dosages; adverse effects; and injection techniques. All Foreign and English language journals were searched. Please refer to Section 2 for search criteria. | |
21762042 | Oestrogen receptor polymorphisms in female patients with rheumatoid arthritis. | 2011 | OBJECTIVES: Rheumatoid arthritis (RA) is a complex autoimmune disease with a strong genetic contribution in its pathogenesis. There is compelling evidence that autoimmunity is under genetic control and that oestrogens and their receptors (ESRs) can play a role in the high prevalence of RA in females. METHODS: A total of 318 female patients with RA and 250 controls were examined. Common single nucleotide polymorphisms (SNPs) in the ESR1 (rs9340799:A>G, rs2234693:T>C) and ESR2 (rs4986938:G>A, rs1256049:G>A) genes encoding oestrogen receptors, previously associated with altered receptor expression, were selected for the purpose of this study. RESULTS: There were no significant differences in the distributions of studied genotypes and alleles between RA patients and a control group. The age at disease diagnosis was lower in carriers of the ESR1 rs9340799 A allele compared with GG homozygotes as well as in patients with ESR1 rs2234693 TT and CT genotypes compared with CC homozygotes. There was no significant association of the genotypes with rheumatoid factor (RF), erosive disease, extra-articular manifestations, or anti-cyclic citrullinated peptide (anti-CCP) antibodies. CONCLUSIONS: The results of the study suggest that polymorphisms in the ESR1 gene may be associated with the age of onset of RA. | |
22515293 | FoxP3 mRNA splice forms in synovial CD4+ T cells in rheumatoid arthritis and psoriatic art | 2012 May | Our aim was to elucidate the relative amount of the different splice forms of FoxP3 mRNA in CD4+ T cells in peripheral blood (PB) compared to synovial fluid (SF) in RA and PsA patients. FoxP3 mRNA was measured using a quantitative real-time PCR method. CD4+ T cells were isolated from 17 paired samples of PB and SF from RA and PsA patients, and PB from 10 controls. FoxP3fl and FoxP3Δ2 mRNA was significantly increased (6.7 and 2.1-fold, respectively) in PB CD4+ T cells from RA patients compared to controls. FoxP3fl and Δ2 mRNA in SF CD4+ T cells was increased compared to controls in sero-negative RA and PsA, but not in sero-positive RA patients, who had a high FoxP3 expression in both PB and SF. The FoxP3Δ2Δ7 mRNA was barely detectable in patient samples, and not at all in healthy individuals. We provide evidence of an increased expression of FoxP3 splice forms in synovial CD4+ T cells from RA patients. A skewed, high expression profile of FoxP3, but not CTLA-4, in sero-negative RA and PsA, indicates that synovial CD4+ T cells may represent unique subsets of T cells which have been induced locally or selectively recruited to the joint. | |
23238605 | Urinary tract infections in patients with rheumatoid arthritis. | 2013 Mar | Co-morbidity from rheumatoid arthritis (RA) has recently focussed on outcomes of cardiovascular and pulmonary disease, but serious infections are an increasingly well-recognised complication of RA. Recent work has demonstrated how the incidence of pneumonia can be reduced in RA, but little attention has been paid to the incidence of urinary tract infection (UTI) in RA or to the associated co-morbidity. The aim of this study was to describe the incidence of UTI leading to hospitalisation in a large cohort of patients with RA and investigate which factors contributed to this. This study assessed all patients with RA hospitalised over a 12-month period with a discharge diagnosis including UTI. Patients were identified through a PAS records search in a single large centre. Historical case controls without RA matched for age and gender were identified from the literature. Clinical notes were manually examined by two observers. We recorded: age, gender, duration of RA, number of UTI, all RA therapy, co-morbidity, results of urine and blood cultures with antimicrobial sensitivities, readmission rates, treatment and outcome. We calculated the relative risk (RR) of developing UTI in patients with RA and the factors influencing this. From a population of 2,200 RA patients, the overall annual incidence of hospitalisation with UTI amongst RA patients was 2.09 %, as against 0.97 and 0.91 % for two control groups (RR = 2.16 and 2.29). Most patients (90 %) were female, and the group mean age was 76 years. The use of long-term oral steroids as sole therapy was associated with a RR of 6.8 for UTI (p = 0.002) while failure to take disease-modifying anti-rheumatic drugs (DMARDs) was associated with a similar RR of 6.7 (p = 0.001). Positive cultures for Escherichia coli were found in 51 % of RA patients. Relevant co-morbidities included permanent catheters, vaginal prolapse, cancer and diabetes. Recurrence of UTI within a year was common. RA was associated with a higher-than-expected incidence of UTI, particularly among older females. This was associated with the use of long-term oral steroids and the absence of DMARDs. Other factors included female gender, greater age and long disease duration. We recommend avoidance of long-term oral steroids but consideration of low-dose prophylactic antibiotics in those patients with recurrent UTI. | |
21390071 | Early gestational gene transfer of IL-10 by systemic administration of lentiviral vector c | 2011 Jul | Gene therapy has been applied to murine models of rheumatoid arthritis (RA) using a number of different strategies to downregulate inflammation in synovial joints. However, prolonged joint expression has been problematic. Our laboratory has found that early gestational intravascular injection of lentiviral vector leads to efficient transduction and sustained transgene expression in articular cartilage and synovium. In this study, we show that in utero gene transfer of IL-10 can prevent and decrease pathology in a murine model of RA. Following prenatal injection of lentiviral vector containing murine IL-10 gene, the cytokine was detectable in the serum, and the green fluorescent protein reporter gene was detectable in chondrocytes and synoviocytes of adult mice up to 21 weeks of age. Adult mice that had been treated prenatally were later immunized against type II collagen to induce an autoimmune arthritis. Compared with controls, prenatally treated mice demonstrated delayed onset of arthritis, decreased frequency of arthritis and markedly decreased severity of disease, by both clinical and histological criteria. This effect was directly related to levels of IL-10 expression, but no immunosuppressive effects of the therapy were observed. This study demonstrates proof of principle for the prenatal prevention and amelioration of RA by early gestational gene transfer of the anti-inflammatory cytokine, IL-10. | |
21937863 | Pyogenic granuloma in a finger of a rheumatoid arthritis patient. | 2011 Jan 21 | Pyogenic granuloma is benign soft tissue tumor which mainly occurs in gingiva, lips, tongue and finger. We report the patient of pyogenic granuloma in the distal phalanx of the index finger of the rheumatoid patient. The tumor enlarged rapidly and surgical excision was performed. Pathological examination showed lobular hyperplasia of capillary vessels and the expression of vascular endothelial growth factor at capillary vessels in inside of tumor. | |
22467937 | Tumor necrosis factor-α inhibitor use is not associated with lipid changes in rheumatoid | 2012 May | OBJECTIVE: To determine the association of use of tumor necrosis factor-α (TNF-α) inhibitors with differences in lipid levels in patients with rheumatoid arthritis (RA). METHODS: We studied 807 patients with incident RA to compare differences in lipid levels in TNF-α inhibitor users versus nonusers, with adjustment for relevant covariables. RESULTS: TNF-α inhibitor use was not associated with differences in levels of low-density lipoprotein (LDL), high-density lipoprotein (HDL), total cholesterol (TC), triglycerides, LDL:HDL, or TC:HDL compared to nonusers. CONCLUSION: Use of TNF-α inhibitor was not associated with differences in lipid levels in patients with RA. | |
21427577 | The value of blocking IL-6 outside of rheumatoid arthritis: current perspective. | 2011 May | PURPOSE OF REVIEW: Interleukin-6 (IL-6) is a multifunctional cytokine that regulates immune response and induces acute phase response. Despite the important physiological activities of IL-6, dysregulated overproduction of IL-6 is pathologically involved in various immune-mediated inflammatory diseases (IMIDs) including rheumatoid arthritis (RA). A series of clinical studies of tocilizumab, a humanized anti-IL-6 receptor (IL-6R) antibody, for patients with RA refractory to conventional therapy or anti-tumor necrosis factor therapy have demonstrated the clinical benefit of IL-6 blockade in RA. On the other hand, there is now accumulating evidence that tocilizumab is therapeutically effective for patients with a number of IMIDs other than RA. This review focuses on the perspective of IL-6 blockade therapy for such IL-6-related IMIDs outside of RA. RECENT FINDINGS: A considerable number of case reports and preclinical studies have shown the benefit of IL-6 blockade therapy in various IMIDs such as systemic lupus erythematosus, adult-onset Still disease, Takayasu arthritis, polyarteritis nodosa, systemic sclerosis, reactive arthritis, dermatomyositis, and polymyositis. SUMMARY: Blocking IL-6 with tocilizumab can be a therapeutic option for patients with various IMIDs in which overproduction of IL-6 plays a pathological role. Future clinical studies investigating the safety and efficacy will elucidate the clinical benefits of IL-6 blockade therapy for such diseases. |