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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20399680 | Modulation of the response of rheumatoid arthritis synovial fibroblasts to proinflammatory | 2010 Jul | Although physical therapy has been shown to be an effective method for treatment of rheumatoid arthritis, a thorough investigation on the impact of mechanical signals upon the complex cytokine network associated with pathogenesis has not yet been conducted. In the current study, our research group investigated the effect of mechanical stimulation on primary and immortalized rheumatoid arthritis synovial fibroblasts (RASFs) through analysis of secreted proteins using multiplex immunoassay. Equibiaxial tensile strain was applied to 2D cultures grown on collagen-coated, flexible silicone membranes at a magnitude of 10% and a frequency of 0.5Hz using the Flexcell System. After 24h, supernatant was removed and assayed for the following cytokines: IL-1beta, IL-6, IL-8, VEGF, FGF-2, GM-CSF, MCP-1, RANTES, TNF-alpha. The results were compared to unstimulated control groups. Mechanical stimulation alone only impacted secretion of IL-8 by primary RASFs. However, in the presence of proinflammatory mediators (TNF-alpha or IL-17), application of cyclic tensile strain increased secretion of a number of proteins by both primary and immortalized RASFs, although the responses were not analogous. In contrast, MCP-1 secretion was decreased when mechanical stimulation was applied in combination with IL-17 to primary cultures. In general, the study suggests that cyclic tensile strain can be used to modulate the effects of proinflammatory stimulants on RASFs; however, given the highly variable results, more research will be necessary to identify the pathways that are implicated in mechanotransduction. | |
19279016 | Cardiovascular risk factors and not disease activity, severity or therapy associate with r | 2010 Mar | OBJECTIVES: The present study aimed to evaluate the prevalence and associations of renal dysfunction in patients with rheumatoid arthritis (RA). It specifically addressed the hypotheses that renal dysfunction in these patients may associate with the presence of insulin resistance, dyslipidaemia, uric acid levels and/or current levels of systemic inflammation. METHODS: Renal function was assessed by estimated glomerular filtration rate (GFR) using the modification of diet in renal disease equation in 400 consecutive RA patients for this cross-sectional, single-centre study. Risk factors for renal dysfunction were recorded/measured in all participants. Correlations between GFR and other variables were analysed by Pearson or Spearman test as appropriate. Linear regression was used to test the independence of the associations between GFR and other variables. RESULTS: In this RA patient cohort, 67.75% of patients had a reduced GFR of less than 90 ml/minute per 1.73 m(2) and 12.75% had a GFR of less than 60 ml/minute per 1.73 m(2). Multivariable analysis revealed significant associations between GFR and age (beta = -0.370, p<0.001), female sex (beta = -0.181, p=0.002), total cholesterol (beta = -0.112, p=0.022), serum uric acid (SUA) (beta = -0.425, p<0.001) and the presence of extra-articular disease, apart from sicca and/or nodules (beta = -0.084, p=0.040). CONCLUSIONS: Renal dysfunction in RA is quite common and associates with classic cardiovascular risk factors such as advanced age and dyslipidaemia, levels of SUA and the presence of extra-articular disease. Renal dysfunction was not related to other RA-related factors including disease activity and duration, disability and past or present use of nephrotoxic medications. | |
19191187 | Combination treatment with leflunomide and methotrexate for patients with active rheumatoi | 2009 Jan | OBJECTIVE: To determine the efficacy and safety of the combination of leflunomide and methotrexate for the treatment of patients with active rheumatoid arthritis (RA) in an open, non-comparative, multicentre trial. METHODS: Seventy-four patients with active RA were enrolled to receive concomitantly leflunomide (no loading dose, 10 mg/day) and methotrexate (starting at 7.5 mg/week and titrating up to 15 mg/week) for 20 weeks. The primary end-point was a 20% improvement in the American College of Rheumatology (ACR) criteria at 20 weeks. Safety measures included evaluation of adverse events at each visit and laboratory data, including haematology and liver function tests. Intention-to-treat analyses were conducted. RESULTS: Sixty-five patients completed 20 weeks of treatment, and 71.6% were responders based on the ACR20 criteria. After 20 weeks, the mean changes were -16.3 for tender joint count, -12.0 for swollen joint count, -44.0 for physician global assessment, -34.3 for patient global assessment, -22.7 for erythrocyte sedimentation rate, and -0.65 for the Health Assessment Questionnaire score. Adverse events occurred in 40.5% of the patients, and were considered serious in four patients who discontinued therapy. Abnormal liver function was noted for 16 patients (21.6%). Two of these patients were withdrawn from the study; after discontinuing the medication, their liver function recovered fully. CONCLUSION: THE combination of leflunomide and methotrexate was effective and well tolerated in the treatment of active RA patients. This combination may be a useful option as an initial treatment for active RA before starting biological agents. | |
19448378 | Extra-articular manifestations of rheumatoid arthritis: a hospital-based study. | 2009 May | BACKGROUND AND OBJECTIVE: The frequency of extra-articular manifestations in rheumatoid arthritis (ExRA) differs from one country to another, so we investigated ExRA frequency in a well-defined hospital patient population with rheumatoid arthritis (RA) in Saudi Arabia. We also examined possible predictors of the development ExRA. METHODS: A retrospective analysis was conducted of all patients diagnosed with RA at a university hospital during a 4-year period. Cases were classified according to the 1987 American College of Rheumatology criteria for RA, and the frequency of ExRA was recorded. RESULTS: Of 140 patients who fulfilled the criteria for the diagnosis of RA, 98 (70%) developed ExRA features. Anemia occurred in 61%, thrombocytosis in 16%, pulmonary involvement in 10%, and renal amyloidosis, vasculitis and Felty syndrome were present in 6%, 2% and 1%, respectively. The mortality rate was high (16%) in patients with ExRA. The predictors for mortality were lung involvement, age over 50 years and kidney amyloidosis. CONCLUSION: ExRA were present in a substantial proportion of our patients, which lead to a worse disease outcome. Anemia, thrombocytosis and respiratory system involvement were the commonest. Early recognition and treatment are important to decrease mortality. | |
19597732 | Are anti-citrulline autoantibodies better serum markers for rheumatoid arthritis than rheu | 2010 Apr | The aim of the study is to evaluate the prevalence of anti-citrulline antibodies (anti-CCP) versus rheumatoid factor (RF) in a cohort of Thai patients with rheumatoid arthritis (RA), a variety of rheumatic diseases other than RA and healthy controls. The association between anti-CCP and RA disease activity was also examined. Serum from 125 RA patients, 60 from other rheumatic diseases (non-RA) and 60 from healthy controls were tested for IgM RF and second generation anti-CCP. The association between anti-CCP, RF, the Disease Activity Score (DAS 28) and other relevant laboratory tests (CBC, ESR and CRP) were assessed. The sensitivity and specificity of anti-CCP antibody were 58.7 and 100% when compared with 63.5 and 98.3% for RF. These differences were not statistically significant. The anti-CCP outperformed RF in terms of the positive-predictive values (100 vs. 97.6%); however, the negative-predictive values were 72.4% for RF and 69.6% for anti-CCP. The sensitivity when either anti-CCP or RF was positive increased to 71.2%. Nine out of 45 RF-negative patients had a positive anti-CCP test. Anti-CCP was significantly correlated with parameters of inflammation, but not with DAS 28. In conclusion, although anti-CCP is better than RF in distinguishing RA from other rheumatic diseases, its cost, which is 3.3 times higher than the RF test precludes it from replacing RF as a serum marker for Thai patients with RA. The treatment decisions cannot be based on the test alone, as it has no correlation with DAS 28. Its usefulness is in patients with suspected RA who have had a negative RF test. | |
19884278 | The anti-mutated citrullinated vimentin response classifies patients with rheumatoid arthr | 2009 Dec | OBJECTIVE: Autoantibodies against citrullinated peptide antigens (ACPA) are routinely determined to diagnose rheumatoid arthritis (RA) and are predictive of a more severe course of the disease. We here set out to address an involvement of ACPA in the pathogenesis of RA and investigated the recognition pattern of antibodies against 2 citrullinated antigens in more detail. METHODS: The sera of 77 patients fulfilling the American College of Rheumatology criteria for RA were analyzed for subclass titers of anti-mutated citrullinated vimentin (MCV) and anticyclic citrullinated peptide (CCP) antibodies by combining subclass specific detection antibodies with commercially available CCP and MCV ELISA plates. Cross-reactivities between anti-MCV and anti-CCP antibodies were detected using a sequential ELISA system. RESULTS: IgG1, IgG3, and IgG4 titers among anti-MCV and anti-CCP antibodies correlated significantly. Cross-reactivity of MCV-specific antibodies against CCP could be detected in 8 of 16 patients' sera; however, cross-binding of MCV-specific IgG4 was weaker compared to total IgG. CONCLUSION: The inherent capacity of IgG4 to exchange F(ab) arms provides insight into the anti-MCV antibody diversity and suggests a classification of ACPA positive patients into broad and narrow responders. | |
20855251 | [Detection and its clinical value of CCR5 and CCR7 in dendritic cells from patients with a | 2010 Sep | OBJECTIVE: To detect the expressions of CCR5 and CCR7 on dendritic cells (DCs) in patients with rheumatoid arthritis (RA) in different phases of disease activity, and explore the relationship between the disease activity and the expression of chemokine receptors. METHODS: Twenty-eight patients with low, moderate and high disease activity and 10 normal control subjects were enrolled in this study. Peripheral blood was obtained from the subjects and the DCs were isolated. The expression of CCR5 and CCR7 on DCs were detected by flow cytometry, and the serum levels of rheumatoid factor (RF), C-reactive protein (CRP) and anti-CCP antibody (ACPA) were assessed. The correlation of the expressions of CCR5 and CCR7 to serum RF, CRP, and ACPA levels of the RA patients were analyzed. RESULTS: Compared to the normal control group, RA patients showed enhanced expressions of CCR5 and CCR7 on the DCs. A linear correlation was noted between CCR5 and CCR7 expressions on the DCs and the serum levels of RF and CRP, but not ACPA, in the RA patients. CONCLUSION: The expressions of CCR5 and CCR7 on the DCs may correlate to the disease activity of RA, and may serve as valuable indices in monitoring the disease activity and the efficacy of the treatment. | |
19969190 | Proliferative extensor tenosynovitis of the wrist in the absence of rheumatoid arthritis. | 2009 Dec | PURPOSE: Proliferative tenosynovitis in the fourth extensor compartment is common in patients with rheumatoid arthritis. It may also occur in the absence of rheumatoid arthritis; the purpose of this study is to describe this clinical condition in a series of patients, to report the results of surgical intervention, and to compare histological findings to those typically seen in rheumatoid tenosynovitis. METHODS: This study presents a retrospective case series of 11 patients who do not have rheumatoid arthritis, who had proliferative tenosynovitis of the fourth extensor compartment treated surgically. Relevant features of the clinical presentation, physical examination, radiographic findings, and results of attempts at conservative treatment are described. Surgical pathology specimens were reviewed by a single pathologist to define common histological features and to compare the histology to that which is classically seen in rheumatoid tenosynovitis. RESULTS: All patients presented with a painful wrist mass over the fourth extensor compartment. Characteristic in physical examination was severe limitation of active wrist extension with the fingers extended, with improvement when the fingers were flexed into a fist. After tenosynovectomy, wrist extension and grip strength improved. Examination of the surgical pathology specimens revealed a spectrum of pathological findings generally consistent with traumatic tenosynovitis, but a few specimens had rheumatoid-like features. CONCLUSIONS: A review of this case series of patients with tenosynovitis but without rheumatoid arthritis demonstrates a distinct clinical condition of exuberant proliferative extensor tenosynovitis blocking proximal tendon excursion, thereby causing pain and limited active wrist extension, as well as a less distinct histological condition with a constellation of findings generally resembling traumatic tenosynovitis. In this group of patients, surgical tenosynovectomy generally yields excellent results. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV. | |
19285366 | [Cutaneous leishmaniasis in rheumatoid arthritis]. | 2009 Jul | INTRODUCTION: Cutaneous leishmaniasis is a protozoal infection. Its prevalence is increasing, especially in immunocompromised subjects. CASE REPORTS: We report four patients with rheumatoid arthritis, treated with methotrexate and prednisone who developed cutaneous leishmaniasis. Clinical outcome was favorable after institution of antimony therapy in three cases despite the continuation of methotrexate and prednisone. One patient failed to respond to therapy. DISCUSSION: The frequency of cutaneous leishmaniasis is increasing especially in immunocompromised subjects. In our patients, rheumatoid arthritis, corticosteroid therapy and methotrexate were predisposing factors of cutaneous leishmaniasis. | |
20229610 | Daytime patterning of fatigue and its associations with the previous night's discomfort an | 2010 Jun | OBJECTIVES: Fatigue is a prominent symptom in many rheumatic diseases and has a substantial impact on many outcomes. In previous research, fatigue has been linked with poor sleep and discomfort, including joint pain and sicca symptoms. The aim of the present study was to investigate prospectively the daily variations in fatigue and the roles of discomfort and adequacy of sleep the previous night in that fatigue for people with primary Sjögren's syndrome (pSS) or rheumatoid arthritis (RA). METHODS: Thirty-nine women with pSS or RA reported their discomfort and fatigue for 35 days using the Profile of Fatigue and Discomfort. Sleep was monitored with wrist actigraphy, and the quantity and quality of the night's sleep was reported in a diary each morning. RESULTS: The pattern of fatigue did not differ significantly between women with pSS and women with RA. For participants with either condition, both somatic and mental fatigue increased steadily throughout the day. Multi-level regressions indicated that evenings of worse discomfort were followed by poorer reported quantity/quality of sleep and worse sleep efficiency (percentage of time asleep when in bed). In addition, a night of worse discomfort and poor sleep was followed by more severe fatigue compared with the individual's average. CONCLUSIONS: Fatigue management for people with rheumatic disease could include strategies for coping with discomfort at night and difficulties in sleeping. Further research into ameliorating fatigue should include assessments of persistent discomfort or periods of insomnia and identify disease-specific needs that require targeted intervention. | |
20614397 | The prothrombotic state in rheumatoid arthritis: an additive risk factor for adverse cardi | 2010 Jun | Rheumatoid arthritis (RA) has been recognized to increase cardiovascular morbidity and mortality independent of established risk factors. The chronic inflammatory state, a hallmark of RA, is considered an autonomous risk factor, whereas components of innate and adaptive immunity are believed to contribute to the onset of acute cardiovascular events. Several studies have suggested that RA confers a prothrombotic state featured by abnormalities in coagulation and fibrinolytic systems together with an altered state of platelet reactivity. It is conceivable that these findings may be partly instrumental for the observed increased risk for adverse cardiovascular events in RA. Therapeutic strategies aimed at attenuating the inflammatory disease activity and intervening at the point of cross-talk between mediators of inflammation and thrombogenesis may help reduce cardiovascular disease burden in patients with RA. | |
20422194 | Risk factors for development and progression of atlantoaxial subluxation in Korean patient | 2011 Oct | We sought to evaluate the frequency of cervical spine (C-spine) involvement, and associated risk factors for this disorder and its progression in Korean patients with rheumatoid arthritis (RA). From 1995 to 2008, we recruited patients with RA attending the rheumatology clinic of a single tertiary care hospital, and evaluated 1,120 of the patients who had neck pain for C-spine involvement. A diagnosis of C-spine involvement was made in 28.6% of patients evaluated, and within this group, anterior atlantoaxial subluxation (AAS) and subaxial subluxation were found in 89.7 and 15%, respectively. Of the 1,120 patients, 570 patients were followed for more than 3 years. Comparing the clinical characteristics of 193 patients with C-spine involvement and 377 patients without C-spine involvement, we found the associations with female gender, RA diagnosis at or before age 45, erosive changes in hand or foot radiographs, C-reactive protein levels and erythrocyte sedimentation rates at the time of first visit, and combination disease-modifying anti-rheumatic drug (DMARD) therapy. We found using logistic regression analysis that significant predictors of C-spine involvement included erosion in hand or foot radiographs (OR = 2.22, p = 0.001) and RA diagnosis at or before age 45 (OR = 2.26, p < 0.001). Among 137 patients followed for more than 3 years, for whom at least two consecutive X-rays were available, we observed radiographic progression in 60.4%. Patients with and without radiologic evidence for cervical progression did not differ significantly in clinical characteristics. In conclusion, Korean patients with RA frequently show radiographic evidence for progressive involvement of the cervical spine. Significant risk factors for C-spine involvement may be associated with erosive peripheral joint disease and RA diagnosis at an early age. | |
20398016 | Endomorphins in rheumatoid arthritis, osteoarthritis, and experimental arthritis. | 2010 Apr | The opioid tetrapeptides endomorphins (EM)-1 and EM-2 are widely expressed in central nervous system and immune tissues of rats and humans. Their analgesic properties are well characterized but they also have anti-inflammatory properties. EM-1 significantly attenuated the onset of hindpaw inflammation in adjuvant-induced arthritis in rats. Immunohistochemical staining demonstrated the presence of EMs in T cells, macrophages, and fibroblasts in synovial tissues from patients with osteo- or rheumatoid arthritis (RA). In an ex vivo superfusion system, EM-1 potently inhibited the release of proinflammatory cytokines interleukin (IL)-6 and IL-8 from synovial tissues from patients with osteo- or RA. These results demonstrate that EMs are endogenously synthesized within human immune cells and have the potential to act as potent therapeutic agents in the treatment of chronic inflammatory disease. We discuss the clinical potential for EM analogues chemically modified to resist proteolytic degradation and identify modified protease-resistant analogues with enhanced bioactivity. | |
20827448 | Pain and mobility improvement and MDA plasma levels in degenerative osteoarthritis, low ba | 2010 | Infrared (IR)-A irradiation can be useful in back and musculoskeletal pain therapy. In this study joint and vertebral column pain and mobility were measured during two weeks of IR-A irradiation treatment of patients suffering from degenerative osteoarthritis of hip and knee, low back pain, or rheumatoid arthritis. Additionally, before and after IR-A treatment MDA serum levels were measured to check if MDA variations accompany changes in pain intensity and mobility. Two-hundred and seven patients were divided into verum groups getting IR-irradiation, placebo groups getting visible, but not IR irradiation, and groups getting no irradiation. In osteoarthritis significant pain reduction according to Visual Analogue Scale and mobility improvements occurred in the verum group. Even though beneficial mean value changes occurred in the placebo group, the improvements in the placebo and No Irradiation groups were without statistical significance. In low back pain, pain and mobility improvements (by 35-40%) in the verum group were found, too. A delayed (2nd week) mobility improvement in rheumatoid arthritis was seen. However, pain relief was seen immediately. In patients suffering from low back pain or rheumatoid arthritis, the pain and mobility improvements were accompanied by significant changes of MDA serum levels. However, MDA appears not a sensitive biofactor for changes of the pain intensity in degenerative osteoarthritis. Nevertheless, unaffected or lowered MDA levels during intensive IR-A therapy argue against previous reports on free radical formation upon infrared. In conclusion, rapid beneficial effects of IR-A towards musculoskeletal pain and joint mobility loss were demonstrated. | |
20158894 | Enhanced late-outgrowth circulating endothelial progenitor cell levels in rheumatoid arthr | 2010 | INTRODUCTION: Angiogenesis and vasculogenesis are critical in rheumatoid arthritis (RA) as they could be a key issue for chronic synovitis. Contradictory results have been published regarding circulating endothelial progenitor cells (EPCs) in RA. We herein investigated late outgrowth EPC sub-population using recent recommendations in patients with RA and healthy controls. METHODS: EPCs, defined as Lin-/7AAD-/CD34+/CD133+/VEGFR-2+ cells, were quantified by flow cytometry in peripheral blood mononuclear cells (PBMCs) from 59 RA patients (mean age: 54 +/- 15 years, disease duration: 16 +/- 11 years) and 36 controls (mean age: 53 +/- 19 years) free of cardiovascular events and of cardiovascular risk factors. Concomitantly, late outgrowth endothelial cell colonies derived from culture of PBMCs were analyzed by colony-forming units (CFUs). RESULTS: RA patients displayed higher circulating EPC counts than controls (median 112 [27 to 588] vs. 60 [5 to 275]) per million Lin- mononuclear cells; P = 0.0007). The number of circulating EPCs positively correlated with disease activity reflected by DAS-28 score (r = 0.43; P = 0.0028) and lower counts were found in RA patients fulfilling remission criteria (P = 0.0069). Furthermore, late outgrowth CFU number was increased in RA patients compared to controls. In RA, there was no association between the number of EPCs and serum markers of inflammation or endothelial injury or synovitis. CONCLUSIONS: Our data, based on a well characterized definition of late outgrowth EPCs, demonstrate enhanced levels in RA and relationship with disease activity. This supports the contribution of vasculogenesis in the inflammatory articular process that occurs in RA by mobilization of EPCs. | |
20190503 | [Management of elderly-onset rheumatoid arthritis]. | 2010 | In addition to population-growth in the elderly, development of new therapeutic agents for rheumatoid arthritis (RA) contributes to an increase in the number of elderly patients with RA. It is also reported that the age of RA onset is going higher. Elderly-onset RA (EORA) is defined as RA developing after the age of 60 years. In RA patients, significant damage can be detected radiographically within the first 2 years after the initial presentation of symptoms; therefore, appropriate treatment should be administered at the earliest. Meanwhile, caution should be exercised in prescribing disease-modifying antirheumatic drugs (DMARDs) to elderly patients because the associated risk of adverse effects and toxicity is elevated in the elderly. However, excessive caution may prevent elderly patients from being implemented the ideal therapy. Compared to young patients with RA, patients with EORA are less frequently treated with biological agents or multiple DMARDs treatment and more frequently treated with prednisone. Some patients with EORA do not receive optimal treatment during the early stage of RA, when the disease is highly active and joint destruction rapidly progresses. EORA should be treated with appropriate DMARDs instead of corticosteroids in order to maintain the risk of infection minimal and the patients' physical function maximal. | |
20235210 | Predictors for remission in rheumatoid arthritis patients: A systematic review. | 2010 Aug | OBJECTIVE: To summarize the potential predictors of remission in patients with rheumatoid arthritis (RA). METHODS: We performed a systematic review of prognostic studies that identified the predictors of remission in RA patients. Studies were identified in Medline, EMBase, and the Cochrane Registry, and by hand search. We included only studies performing multivariate analysis. RESULTS: A total of 18 studies from 2,062 citations were included. The following variables were found to be the independent predictors of RA remission: male sex; young age; late-onset RA; short disease duration; nonsmoker; low baseline disease activity; mild functional impairment; low baseline radiographic damage; absence of rheumatoid factor and anti-citrullinated peptide; low serum level of acute-phase reactant, interleukin-2, and RANKL at baseline; MTHFR 677T alleles and 1298C alleles in the methotrexate (MTX)-treated patients; magnetization transfer ratio 2756A allele +/- either the SLC 19A180A allele or the TYMS 3R-del6 haplotype in the MTX plus sulfasalazine combination-treated patients; early treatment with nonbiologic disease-modifying antirheumatic drug (DMARD) combinations; the use of anti-tumor necrosis factor (anti-TNF); the concurrent use of DMARDs in anti-TNF-treated patients; and moderate or good response to treatments at the first 6 months. The magnitude of the association in the individual predictor was diverse among the studies depending on the patient characteristics, the study characteristics, and the variables used to adjust for in the models. CONCLUSION: A number of independent predictors of remission, i.e., baseline clinical and laboratory characteristics and genetic markers, were summarized. The predictive value of prognostic factors recently identified needs to be confirmed. | |
19944780 | The environment, geo-epidemiology, and autoimmune disease: Rheumatoid arthritis. | 2010 Mar | Rheumatoid arthritis (RA) is a chronic inflammatory joint disease characterized by a distinctive pattern of bone and joint destruction. RA patients have an increased risk of death. The incidence and prevalence of RA vary across populations, statistical methods, and disease definitions. In North America and Northern Europe, the incidence of RA is estimated at 20 to 50 cases per 100,000 population and the prevalence at 0.5% to 1.1%. Lower incidences and prevalences have been reported in Southern Europe, and few data are available for developing countries. Some studies showed declining incidences and prevalences after the 1960s. RA is a multifactorial disease that results from interactions between genetic and environmental factors. The main genetic factors are HLA-DRB1 and the tyrosine-phosphatase gene PTPN22. Among environmental factors implicated in the development of RA, smoking shows the strongest association with RA susceptibility and is also linked to worse outcomes. The aim of this review is to discuss the available data on the incidence and prevalence of RA, as well as the genetic and environmental risk factors associated with RA. | |
20031469 | Prevalence and significance of MEFV gene mutations in a cohort of patients with rheumatoid | 2010 Jan | OBJECTIVES: Pyrin/marenostrin, an inhibitory regulator of inflammation, is encoded by MEditerranean FeVer (MEFV) gene. Mutations of this gene are the cause of familial Mediterranean fever (FMF). A connection between MEFV gene mutations and rheumatic diseases has been suggested. The aim of this study was to explore the frequency and clinical significance of MEFV gene mutations in a cohort of Turkish patients with rheumatoid arthritis (RA). METHODS: The study included 103 patients with RA and 103 age-, sex- and origin-matched healthy controls (HC). In all participants, genomic DNA was isolated and genotyped using amplification refractory mutation system or restriction fragment length polymorphism for the eight MEFV gene mutations (E148Q, M694V, M694I, M680I, V726A, A744S, R761H, and P369S). In the RA group, disease activity was determined using the disease activity score-28 (DAS-28), and radiological damage was evaluated by the modified Larsen scoring method. RESULTS: Carrier rates of MEFV gene mutations were 26/103 (25.2%) and 24/103 (23.3%) in the RA and HC groups, respectively (p>0.05, OR: 0.9, 95% CI: 0.48-1.71). In the RA group, while deformed joint count was significantly higher in the mutation carrier group than those of the non-carrier group (p<0.05), the level of C-reactive protein, DAS-28 and modified-Larsen scores were slightly but not significantly higher in the carrier group. CONCLUSION: The results of this study suggest that MEFV gene mutations appear to be an aggravating factor for the severity of RA, and consequently, patients with RA might be screened for MEFV gene mutations in countries where FMF is frequent. Whether the searching of MEFV gene mutations in RA patients is cost-effective deserves further investigations. | |
19662401 | Extensor tendon rupture and three-dimensional computed tomography imaging of the rheumatoi | 2010 Apr | PURPOSE: Extensor tendon rupture on the dorsum of the wrist is commonly seen in patients with rheumatoid arthritis (RA). The diagnosis of tendon rupture is usually straightforward, but it is sometimes difficult in the hand with complex deformity. The purposes of this study were to investigate the reliability of three-dimensional computed tomography (3DCT) imaging of extensor tendons in the rheumatoid wrist and in the normal wrist and to clarify the validity of its clinical application to the diagnosis of tendon rupture in the rheumatoid wrist. METHODS: Preoperative 3DCT images of 48 wrists of 45 patients with RA and 3DCT images of 38 wrists of 38 healthy volunteers were reviewed retrospectively by six orthopaedic surgeons who were unaware of all other study data. Extensor tendon rupture was verified by operation on 20 rheumatoid wrists. RESULTS: Regarding interobserver and intra-observer reliabilities of 3DCT imaging of the extensor tendons, agreement with respect to tendon rupture in this study group was high, and Cohen's kappa (kappa) coefficient was variable, depending on the individual tendon. Positive predictive value (PPV) of tendon rupture in the extensor digiti minimi (EDM), extensor digitorum communis (EDC) V and IV and extensor pollicis longs (EPL) tendons was more than 60%, but those for the other extensor tendons were less than 50%. Negative predictive value (NPV) was more than 96% in all extensor tendons, in both rheumatoid and normal wrists. CONCLUSIONS: Extensor tendons in normal and rheumatoid wrists were well depicted by 3DCT imaging. In the rheumatoid wrists, extensors of the ring and little fingers and the thumb were depicted more accurately than those to the other fingers. 3DCT imaging was clinically applicable to wrists for which it was difficult to diagnose by physical examination a definite cause for the loss of extension of the fingers. |