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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19811293 | Apoptosis-related changes in plasma membrane glycoconjugates of peripheral blood lymphocyt | 2009 May | Control of apoptosis (apo) is very important for diagnosis, prognosis and treatment of rheumatoid arthritis (RA). Recently, we found that an appearance of specific cell surface GC is attributable to apo and developed lectin-induced agglutination test for apo evaluation. The aim of current study was to estimate changes in surface GC expression in peripheral blood lymphocytes (PBL) of normal healthy donors (NHD) and patients with RA, measured by cell agglutination with the galactose-specific VAA lectin and by lectin-cytochemical analysis. In parallel, these changes in apo incidence were evaluated by the detection of cells with sub-G1 DNA content. The data revealed an increased level of apo in lymphocytes of RA patients (n = 29), and increased cell surface GC expression in lymphocytes of NHD (n = 18). A correlation (R = 0.708) was observed between these two indicators. Specific changes in cell surface GC can be effectively used for the detection of apo cells in RA and other autoimmune disorders. | |
20500344 | The sources of disease-related information for Estonia's rheumatoid arthritis patients: a | 2010 May | OBJECTIVE: To describe rheumatoid arthritis patients' perceptions of being informed and of the value of the information obtained. BACKGROUND: About the accessibility of the disease-specific information to the patients, a prerequisite for any kind of the patient empowerment, can be considered as a priority area for investigation. DESIGN: Six focus groups (involving 27 patients) were conducted. For analysing the data, thematic analysis was applied. RESULTS: The participants referred to the media and the Internet, in-patient units, physicians at out-patient consultations, patients organisations, fellow patients and their own experience as the sources of disease-related information. The information delivered by the physicians was valued highest; satisfaction with the information received from the in-patient units was expressed. The knowledge acquired through the experience was mentioned as being important for coping with the disease. The media was an easily accessible information channel, although the information from this source was less trusted. The access to the Internet was seen as being limited for certain patients groups. The availability of physician-delivered information was described as unsatisfactory due to the organisation of information transmittal in out-patient settings. CONCLUSIONS: The results indicated the current balance of information sources as being incongruous with the provision of systematic and reliable disease-related information. The available information may also be qualitatively incomplete. RELEVANCE TO CLINICAL PRACTICE: Recognition of the weak and strong points of the structure of information provision is valuable when considering the development of educational opportunities for rheumatoid arthritis patients. | |
19657663 | [Anti-inflammatory and analgesic electrotherapy. Evidence in rheumatology?]. | 2009 Sep | The objective of this article is an assessment of the evidence on antiinflammatory and analgesic current in rheumatology. Three trials on the effects of TENS (transcutaneous electrical nerve stimulation) with RA-patients (rheumatoid arthritis) showed good analgesic effect, while one study on EMS (electrical muscle stimulation) demonstrated a benefit in muscle strength and function. No anti-inflammatory effect could be verified. The overall validity is limited due to the small number of studies and the methodical quality of the analyzed trials. | |
19540364 | Peptidylarginine deiminase 4 and citrullination in health and disease. | 2010 Jan | Deimination is catalyzed by a family of calcium binding enzymes, called peptidylarginine deiminases (PADs). Among these, the PAD4 isoform has been more extensively studied for its role in some autoimmune diseases. PAD4 is localized in the cytoplasm of monocytes, T and B cells, neutrophils, eosinophils and NK cells and can move to the nucleus upon cell activation. PAD4 plays a physiological role in gene regulation via citrullination of histones. In rheumatoid arthritis (RA), PAD4 contributes to the generation of ACPA specific substrates and is itself a target of autoantibodies; alleles of the PADI4 gene confer susceptibility to RA in Asians but not in Caucasians. In multiple sclerosis, extensive deimination of brain proteins is observed in active lesions, but no role for the PADI4 gene in susceptibility to MS has been so far described. | |
19459564 | [Influence of balneophysical therapy on activity, functional capacity, and quality of life | 2009 Mar | INTRODUCTION: It has been well known that balneophysical therapy has a therapeutic effect on clinical and biological parameters of disease activity in the patients with rheumatoid arthritis (RA). OBJECTIVE: To determine the influence of balneophysical therapy on functional capacity, activity and quality of life of the patients with RA primarily treated with some of disease modifying antirheumatic drugs. METHODS: The study enrolled 73 patients with RA treated with some of disease modifying antirheumatic drugs (Methotrexate in 85% of patients). During hospitalization at the Clinical Rheumatologic Department of the Institute "Niska Banja", the patients were treated, beside the medicamentous therapy, by hydrotherapy (oligomineral, homeothermic, low radioactive water), mineral peloid therapy, electrotherapy and kinesiotherapy. Before and after balneotherapy, the patients filled in the Health Assessment Questionnaire (HAQ) and the Quality of Life Rheumatoid Arthritis (QOL-RA) scale. The Disease Activity Score (DAS) 28 was used to measure the disease activity before and after balneotherapy. A possible value of HAQ was from 0 to 3, and QOL-RA from 0 to 10. RESULTS: The mean value of the duration of balneophysical therapy was 14.7 +/- 4.8 days. We found significant improvement of functional capacity in the patients with RA. The average HAQ score before balneotherapy was 1.07 +/- 0.61, and 0.86 +/- 0.55 after balneotherapy, which was statistically significantly lower (p < 0.05). DAS 28 after balneotherapy was also statistically significantly lower than DAS 28 before balneotherapy: the mean value of DAS 28 before therapy was 6.30 +/- 0.81 and after therapy 5.48 +/- 0.75 (p < 0.001). The quality of life significantly improved after balneophysical therapy: the mean value of QOL-RA scale before therapy was 5.38 +/- 1.62 and after therapy 7.35 +/- 1.81 (p < 0.05). CONCLUSION: Balneophysical therapy, when properly dosed, is an effective, adjuvant therapy in the patients with RA of mild disease activity. Balneophysical therapy has a positive influence on disease activity, functional capacity and quality of life in the patients with rheumatoid arthritis. | |
20163026 | [Rheumatoid arthritis diagnosis based on the detection of a pulmonary rheumatoid nodule in | 2010 Jan | A 77-year-old man with Hansen's disease was referred to our hospital because of a small nodular lesion detected adjacent to the pleura in the right lower lobe (S10) on chest CT. He had lost all ten fingers due to Hansen's disease and was using a prosthetic limb after amputation of the right lower leg. Although the patient had an 11-year history of shoulder and back pain and was suspected of having interstitial pneumonia 6 years previously, no detailed examination had been conducted. Bronchoscopy did not yield a definitive diagnosis, and a lung biopsy was performed under thoracoscopic guidance. Histological examination of the resected nodule with colliquative necrosis revealed palisading granulomas with multinucleated giant cells and plasma cell infiltration with formation of lymphoid follicles. Since serum levels of both anti-MMP3 and anti CCP antibodies were elevated, rheumatoid arthritis (RA) with rheumatoid lung was diagnosed. Therefore, the nodule was considered a rheumatoid nodule. Since diagnosis of rheumatoid arthritis is difficult when lacking characteristic joint manifestations, it is important to include rheumatoid nodules as a differential diagnosis and to measure RA specific autoantibodies, to make a comprehensive diagnosis for non-specific necrotizing granulomas. | |
19346220 | Measure of function in rheumatoid arthritis: individualised or classical scales? | 2010 Jan | BACKGROUND: The Health Assessment Questionnaire Disability Index (HAQ-DI) is the most widely used measure of function in rheumatoid arthritis (RA). OBJECTIVE: To evaluate individualised forms of the HAQ-DI and thus enhance the incorporation of patients' views in outcome assessment. PATIENTS AND METHODS: HAQ-DI data were prospectively obtained from 370 outpatients with RA treated with leflunomide over a 6-month period. At baseline and final visits, patients had to rate the importance they attached to each activity addressed by the 20 HAQ-DI items, and to select the five activities they considered the most important. Different individualised scales were evaluated: scales preserving all domains, in which the score for each item is multiplied by or added to its importance; and scales involving, for each patient, only the five most important items. The psychometric properties of these scales were compared with those of the HAQ-DI. RESULTS: For each HAQ-DI item, severity and importance scores were weakly correlated. Scores for all individualised scales were highly correlated with the HAQ-DI score (r(s)>0.75). All scales had a good internal consistency (Cronbach's alpha 0.87-0.88). Compared with the HAQ-DI, individualised scales did not have better sensitivity to change (standardised response mean 0.64-0.69 vs 0.74). CONCLUSION: Individualised scales have similar properties to the HAQ-DI. However, individualised questionnaires measuring importance gave complementary information to the measure of disability. Individualisation is probably not needed for group assessment in all randomised controlled trials but, the use of individualised questionnaires may be clinically relevant for individual patients with RA. | |
20032229 | Prediction of functional impairment and remission in rheumatoid arthritis patients by bioc | 2010 Mar | OBJECTIVE: To develop a model to predict RA outcome based on biochemical variables and single nucleotide polymorphisms (SNPs). METHODS: We collected baseline data from RA patients. SNP genotyping was performed using an oligonucleotide microarray. Remission and severe disability were investigated as outcomes of the study. Logistic regression models and receiver operating characteristic (ROC) curves were used to determine sensitivity (S), specificity (Sp) and likelihood ratio (LR). RESULTS: Six hundred and thirty-two patients (375 in the study and 257 in the validation) were included. Twenty-two out of 152, and 19 out of 208 patients had an HAQ > 2. The model obtained to predict disability included levels of the anti-cyclic citrullinated peptide (anti-CCP) antibodies, ESR and SNP rs2070874 in the IL-4 gene. Homozygous and heterozygous carriers of the IL-4 33T allele had a decreased risk of severe disability. The discriminative power had an area under the curve (AUC) of 0.792 (95% CI 0.694, 0.889), with S 41%, Sp 95% and LR +7.6. Twenty-one out of 268 and 17 out of 211 patients were in remission in the study and validation cohorts, respectively. The model included absence of anti-CCP antibodies and the SNP rs2476601 on the PTPN22 gene. Homozygous and heterozygous carriers of the PTPN22 1858T allele had a decreased probability of remission. The discriminative power had an AUC of 0.842 (95% CI 0.756, 0.928), with S 76%, Sp 86% and LR + 5.4. Predictive ability was confirmed on the validation cohort. CONCLUSIONS: We have developed two models based on laboratory variables that are associated with relevant outcomes for RA patients at disease onset. | |
19524474 | Diagnostic and prognostic usefulness of antibodies to citrullinated peptides. | 2009 Jul | The diagnosis of rheumatoid arthritis (RA) must be made early, because prompt initiation of treatments tailored to disease activity is crucial to improve structural and functional outcomes. Anti-citrullinated peptide antibodies (ACPAs) are well-established diagnostic markers for RA and should be included in the classification criteria. Here, we describe the main tests for detecting ACPAs and we underline the diagnostic and prognostic usefulness of ACPAs in patients with RA. The presence of ACPAs predicts poorer functional and structural outcomes, and ACPA titers respond to some of the medications used in RA. Therefore, ACPA titers should be determined at regular intervals throughout follow-up. | |
19877106 | Functional and work outcomes improve in patients with rheumatoid arthritis who receive tar | 2009 Nov 15 | OBJECTIVE: Work disability is a serious consequence of rheumatoid arthritis (RA). We conducted a 6-month, prospective randomized controlled trial comparing assessments of function, work, coping, and disease activity in employed patients with RA receiving occupational therapy intervention versus usual care. METHODS: Employed patients with RA with increased perceived work disability risk were identified by the RA Work Instability Scale (WIS; score >or=10). Patients were stratified into medium- (score >or=10 and <17) and high-risk (>or=17) groups, then randomized into occupational therapy or usual care groups. Assessments were conducted at baseline and 6 months. The primary outcome was the Canadian Occupational Performance Measure (COPM), a standardized patient self-report of function. Other outcomes included the disability index (DI) of the Health Assessment Questionnaire (HAQ); Disease Activity Score in 28 joints (DAS28); RA WIS; EuroQol Index; visual analog scales (VAS) for pain, work satisfaction, and work performance; and days missed/month. Independent sample t-tests and Mann-Whitney U tests were used. RESULTS: We recruited 32 employed patients with RA. At baseline the groups were well matched. At 6 months the improvement in the occupational therapy group was significantly greater than that in the usual care group for all functional outcomes (COPM performance P < 0.001, COPM satisfaction P < 0.001, HAQ DI P = 0.02) and most work outcomes (RA WIS [P = 0.04], VAS work satisfaction [P < 0.001], VAS work performance [P = 0.01]). Additionally, Arthritis Helplessness Index (P = 0.02), Arthritis Impact Measurement Scales II pain subscale (P = 0.03), VAS pain (P = 0.007), EuroQol Index (P = 0.02), EuroQol global (P = 0.02), and DAS28 (P = 0.03) scores significantly improved. CONCLUSION: Targeted, comprehensive occupational therapy intervention improves functional and work-related outcomes in employed RA patients at risk of work disability. | |
19449475 | [Diagnosis and therapeutical management offered to rheumatoid arthritis patients in Brazil | 2009 Jan | OBJECTIVES: The aim of this study was to evaluate in relation to diagnosis and treatment for Rheumatoid Arthritis (RA) patients Brazilian population, and compare the management offered to patients who are followed up in the public and private sectors. MATERIAL AND METHODS: An electronic questionnaire was sent to 650 rheumatologists, members of the Brazilian Rheumatology Society (SBR) and who were attending adult RA patients in the public and/or private sector, who had a contact e-mail address available in the SBR register and agreed to take part in the survey. RESULTS: The rheumatologists estimated that 51.7% of the patients had had their disease diagnosed and of these, 56.1% were undergoing treatment. It was also estimated that 53.9% of the RA patients that was under treatment were being followed up by rheumatologists. The mean time interval estimated by the rheumatologists, between the appearance of the first symptoms of RA and the diagnosis made by a doctor, was greater among the patients who sought attendance in public services (1.8 years). There was no difference in clinical and radiographic assessment measures between the two types of service, with the exception of the application of HAQ, which was used more in public services. The principal drug association reported in both types of services was methotrexate and chloroquine. The rate of usage of associations between biological agents and methotrexate ranged from 6 to 8%. The main treatment-related difficulties were: access to the health system (public services) and cost of medication (private services). CONCLUSION: Approximately 50% of RA patients are being diagnosed and half of these are under treatment. There was no great difference in attendance within the public and private systems for these patients, whereas the main difficulty for the public system was access to attendance, for the private system it was the cost of the medication. | |
20859223 | Abatacept therapy for rheumatoid arthritis in the setting of hepatitis C infection. | 2010 Oct | Chronic hepatitis C in the setting of rheumatoid arthritis may be an obstacle to optimal management because of potential hepatotoxicity and adverse effects from immune suppression in these patients with a chronic infection. There are no reports in the literature discussing the use of abatacept, a T-cell costimulatory blocker, in patients with chronic hepatitis C. This article is the first report to describe the use of abatacept in 2 patients with rheumatoid arthritis and concomitant hepatitis C with favorable outcome. | |
18957489 | Test-retest reliability of disease activity core set measures and indices in rheumatoid ar | 2009 Jun | AIM: To examine the test-retest reliability of the rheumatoid arthritis (RA) core disease activity measures and derived composite indices. METHODS: A total of 28 stable patients with RA had 2 complete assessments within 1 week, which included the 7 RA core disease activity measures and derived disease activity indices (28-joint Disease Activity Score (DAS28), Simplified Disease Activity Index (SDAI), Clinical Disease Activity Index (CDAI), RA Disease Activity Index (RADAI) and Routine Assessment of Patient Index Data (RAPID3)). The intraclass correlations (ICC), the smallest detectable difference (SDD) and minimal detectable change as percentage of the maximum score (MDC%) were estimated as measures of test-retest reliability. RESULTS: Correlations for the disease activity indices were high. SDDs (MDC%) to detect a true improvement or deterioration with 95% confidence were: DAS28 1.32 (14.4%), SDAI 8.26 (9.6%), CDAI 8.05 (10.6%), RAPID3 1.48 (14.8%) and RADAI 1.49 (14.9%). Thus, SDDs were rather high, and the MDC% values were of a similar magnitude of 10% to 15% for all seven core data set measures. CONCLUSIONS: SDDs of the DAS28, SDAI and CDAI were close to limits to detect important improvement. Clinicians should be aware of measurement error. Nonetheless, RA core data set measures and indices obtained from a health professional, laboratory and patient self-report had similar reliability. | |
19578646 | The effect of 677C>T and 1298A>C MTHFR polymorphisms on sulfasalazine treatment outcome in | 2009 Jul | Despite the availability of several new agents for the treatment of rheumatoid arthritis (RA), sulfasalazine remains the mainstay because of both cost and experience with its use. Methylenetetrahydrofolate reductase (MTHFR) is involved in folate metabolism and several polymorphisms have been described in the MTHFR gene. Of these, the 677C>T and 1298A>C polymorphisms have been associated with altered enzyme activity. To examine the association between 677C>T and 1298A>C MTHFR polymorphisms and sulfasalazine efficacy for the treatment of RA, a total of 117 RA patients treated with sulfasalazine (1 g daily; duration of treatment 17 +/- 5 months) were analyzed. The 677C>T and 1298 A>C polymorphisms were detected using a PCR-RFLP method. RA was diagnosed according to the criteria of the American College of Rheumatology (ACR). The remission of RA symptoms was evaluated according to the ACR 20% response criteria. Allele and genotype frequencies were compared by the two-sided Fisher exact test. The frequency of remission was 47.2% and 44.6% in carriers of 677T and 1298C alleles, compared to 40.7% and 42.0% in carriers of 677C and 1298A alleles, respectively. These differences were statistically non-significant. When the multivariate analysis was additionally adjusted for patients' age, gender and RA duration, the association of the MTHFR 677T allele with increased frequency of remission was statistically significant. Although RA remission rate in carriers of the MTHFR 677T and 1298C alleles was more frequently observed, it does not seem that 677C>T and 1298A>C MTHFR polymorphisms have a major influence on treatment outcome in RA patients treated with sulfasalazine. | |
19521743 | Diffuse chronic leptomeningitis with seropositive rheumatoid arthritis: report of a case s | 2009 | A case of biopsy-confirmed chronic leptomeningitis complicating rheumatoid arthritis in a 53-year old female is reported. Her symptoms included weight loss, severe depression, and pyrexia. Magnetic resonance imaging was useful in diagnosis. Intravenous methylprednisolone was prescribed (1 g/day for 3 days), followed by prednisolone (initial dose of 30 mg daily), and this treatment was effective. Her IgG-index, serum levels of soluble interleukin-2 receptor and ferritin, and cerebrospinal level of interleukin-6 paralleled her clinical course. | |
20838835 | The continuous measurement of anti-CCP-antibodies does not help to evaluate the disease ac | 2010 Dec | Anti-cyclic citrullinated peptide antibody (CCP-AB) are used for diagnosis of rheumatoid arthritis (RA). It is still unknown if the extent of CCP-AB levels is useful to assess the disease activity or the individual follow-up as an individual activity parameter. We investigated 40 patients with a known RA who were positive for CCP-AB. Correlation between disease activity (DAS 28) and the amount of levels of CCP-AB in all patients over time as well as the individual follow-up were analysed. A weak correlation between CCP-AB and DAS 28 [r = 0.19; p = 0.001] was found. The individual correlation between CCP-AB titre and DAS 28 ranged between r = -1 and r = 1, so a strong positive and also a strong negative correlation was seen in single patients. In patients with erosive RA the correlation was significantly more positive than in patients with non-erosive RA. Because the correlation between CCP-AB levels and parameters of disease activity measured by DAS 28 is very low, we conclude for monitoring the disease activity to use simply and established parameters like morning stiffness, HAQ or ESR. The individual follow-up of the levels of CCP-AB is by the moment not useful for monitoring the disease activity. | |
19901918 | Vascular effects of biologic agents in RA and spondyloarthropathies. | 2009 Dec | Endothelial dysfunction and accelerated atherosclerosis lead to increased cardiovascular morbidity and mortality in patients with rheumatoid arthritis and other inflammatory rheumatic diseases. Sustained inflammation is a major risk factor for cardiovascular disease. Apart from traditional vasculoprotective agents, biologic agents may also exert favorable effects on the vasculature. Indeed, agents that inhibit tumor necrosis factor (TNF) seem to transiently improve endothelial function. Data regarding the effects of biologic agents on atherosclerosis and arterial stiffness are inconsistent. The effects of the various TNF blockers on dyslipidemia might differ: long-term infliximab therapy could be pro-atherogenic, whereas some studies suggest that etanercept and adalimumab may exert beneficial effects on the lipid profile. TNF blockers have been shown to decrease the incidence of cardiovascular events in patients with rheumatoid arthritis. Preliminary data suggest that rituximab also improves endothelial function and dyslipidemia. Further studies are needed to determine the net effects of biologic agents on the vasculature. | |
19902562 | Purine biosynthetic pathway genes and methotrexate response in rheumatoid arthritis patien | 2009 Oct | OBJECTIVE: Inter-individual variations to methotrexate (MTX) response among rheumatoid arthritis (RA) patients have been attributed to clinical heterogeneity and genetic variations influencing MTX pharmacology. In this study, we analyzed the association of polymorphisms in ATIC, AMPD1, ADA, and ADORA2A from the purine biosynthetic pathway with MTX response in RA patients from north India. We also assessed the cumulative contribution of these polymorphisms together with those from the receptor-metabolizer-transporter and folate pathway genes that we have previously investigated. METHODS: RA patients recruited using the American College of Rheumatology criteria were grouped into good (n = 213) and poor (n = 68) responders to MTX, based on Disease Activity Score 28-3. Individual single nucleotide polymorphism association was tested using (chi)2 test, and cumulative contribution of all the single-nucleotide polymorphisms and cumulative contribution of all the SNPs and clinico-demographic factors were assessed using linear and logistic regression. RESULTS: G allele of ADA rs244076 [P = 0.02, odds ratio (95% confidence interval): OR (95% CI) = 1.66 (1.01-2.75)]; and T allele of ADORA2A rs5751876 [P = 0.04, OR (95% CI) = 1.55 (1.01-2.37)] were associated with poor response, but did not stand Bonferroni correction. On regression analyses, FPGS rs1544105, TYMS rs2853539, DHFR rs7387, and ADA rs244076 were identified as putative predictors for MTX response. Carriers of the FPGS rs1544105 AA and AG genotypes [OR (95% CI) = 3.47 (1.19-10.12)] and TYMS rs2853539 AA genotype [OR (95% CI) = 2.76 (1.50-5.07)] were predictors of poor response in our patient population. CONCLUSION: Genes from all the three pathways seem to contribute to MTX response in the Indian population. However, these observations need to be replicated in an independent sample set. | |
20959025 | Histone deacetylases in RA: epigenetics and epiphenomena. | 2010 | Reduced synovial expression of histone deacetylases (HDACs) is proposed to contribute to pathology in rheumatoid arthritis (RA) by enhancing histone-dependent access of transcription factors to promoters of inflammatory genes. In the previous issue of Arthritis Research & Therapy, Kawabata and colleagues provided independent evidence that HDAC activity is increased in the synovium and fibroblast-like synoviocytes (FLSs) of patients with RA and is paralleled by increased HDAC1 expression and synovial tumor necrosis factor-alpha (TNFα) production. Remarkably, stimulation of RA FLSs with TNFα specifically increases HDAC activity and HDAC1 expression, suggesting that changes in synovial HDAC activity and expression may be secondary to local inflammatory status. | |
20049446 | Comparison of the second and third generation anti-cyclic citrullinated peptide antibody a | 2011 May | The anti-cyclic citrullinated peptide (CCP) antibody has become increasingly important in the diagnosis of rheumatoid arthritis (RA), especially for early diagnosis. The purpose of this study is to compare the diagnostic usefulness of the second and third generation anti-CCP antibody kits among Japanese patients with RA. Anti-CCP antibody titers were measured with the second generation (MESACUP CCP test, Medical and biological laboratories) and third generation (QUANTA Lite CCP3 IgG ELISA, Inova Diagnostics) kits using serum samples from 106 rheumatoid arthritis (RA) patients and 57 non-RA patients. Sensitivities and specificities were compared. The sensitivity and specificity of the second generation anti-CCP (anti-CCP2) kit were 88.7 and 89.5%, and those of the third generation anti-CCP (anti-CCP3) kit were 91.5 and 87.7%. Area under the receiver operating curve showed that anti-CCP2 and anti-CCP3 had similar diagnostic performances. Diagnostic performance of the anti-CCP3 assay was comparable with the anti-CCP2 assay in Japanese patients with RA. |