Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 12510350 | [Predictive factors of prognosis in rheumatoid arthritis]. | 2002 Dec | Rheumatoid arthritis leads the patients to severe physical disability and the mortality is significantly worse than general population. To predict the prognosis at first visit in hospital is difficult but there are several factors influence on the prognosis; disease activity and it's duration, high titer of rheumatoid factor, male and vasculitis. The most important factor is disease activity and it's duration. Recent advance of the treatment of RA improve the prognosis of either disability or mortality. Adverse effects of drugs for RA may threaten the life but their use leads statistically significant improvement of mortality. | |
| 15643570 | Magnetic resonance imaging of the synovium in rheumatoid arthritis. | 2004 Dec | Early diagnosis, followed by early initiation and optimal adjustments of aggressive therapies, are acknowledged as essential to optimize long-term clinical and radiological outcome in rheumatoid arthritis (RA). This requires sensitive methods for detection and monitoring of the primary feature of RA--the synovitis. In comparison with conventional methods, magnetic resonance imaging (MRI) offers assessment of the rheumatoid synovium with improved sensitivity to early pathology and to change. Various aspects such as volume, vascularity, and edema can be assessed by different metrological approaches. MRI findings are of prognostic value to the long-term radiological outcome. This article reviews current knowledge on MRI for assessment of the synovium in RA, focusing on the validity of MRI measures of synovitis. Future perspectives and suggested research priorities are described. The rationale is provided for MRI becoming the new gold standard for assessment of RA joints and for MRI assessments of synovitis being reliable and valid measures of rheumatoid disease activity. | |
| 12117683 | An eight year prospective study of outcome prediction by antiperinuclear factor and antike | 2002 Aug | OBJECTIVES: Antikeratin antibodies (AKA) and antiperinuclear factor (APF) are specific antibodies found very early in rheumatoid arthritis (RA). The objective of this eight year follow up study was to assess the value of early AKA and APF assays in predicting functional disability and cartilage damage. METHOD: In 2000, 64 patients tested for AKA and APF (antifilaggrin antibodies) between 1990 and 1993 during evaluation of early symmetric oligoarthritis or polyarthritis (suspected RA) were invited to participate in this non-concurrent cohort study. The Health Assessment Questionnaire (HAQ) score, disease activity score (DAS), and Larsen radiographic score were the primary evaluation criteria. RESULTS: Twenty nine patients were re-evaluated. Clinical and laboratory data obtained in 1993 were similar in this group and in the 35 other patients. Twenty five patients had received a diagnosis of RA. Nine (31%) were rheumatoid factor (RF) positive, nine (31%) were AKA positive, and six (21%) were APF positive during the first year of the disease. APF was correlated with the Larsen score (p=0.011) and DAS (p=0.035) evaluated after a mean disease duration of 8.55 years. All APF positive patients had erosive disease. AKA was correlated with the DAS (p=0.035). CONCLUSION: The presence of AKA or APF early in the course of RA was associated with the DAS or Larsen score eight years later. The number of patients was small, but the findings confirmed those of studies with shorter follow ups. Antifilaggrin antibodies should be included in the initial investigation of patients with RA and, when positive, should alert to a high risk of poor outcomes. | |
| 14990818 | Rheumatoid arthritis: epidural enhancement as an underestimated cause of subaxial cervical | 2004 Apr | PURPOSE: To assess the frequency and site of subaxial spinal canal stenosis due to enhancing tissue in patients with rheumatoid arthritis. MATERIALS AND METHODS: Data from 33 consecutive patients with rheumatoid arthritis were evaluated; these patients had undergone 1.5-T magnetic resonance imaging following gadolinium chelate administration, in combination with a frequency selective fat-suppression technique. Stenosis and enhancement were scored for each of six cervical spinal levels and were compared with results in a control population consisting of 16 patients with degenerative disease. Enhancement was scored as superficial or deep on the anterior and posterior sides from the cervical spinal cord. Differences between patient groups were tested by using the chi(2) test for trend and the Fisher exact test. RESULTS: No significant difference was found in the frequency or severity of subaxial stenosis between rheumatoid arthritis and degenerative disease. Deep epidural enhancement was observed more often with rheumatoid arthritis than with degenerative disease both anterior (25 of 33 patients vs seven of 16 patients, respectively; P <.001) and posterior (24 of 33 patients vs two of 16 patients, respectively; P =.001) to the spinal cord. Enhancing stenosing tissue in rheumatoid arthritis frequently occurred anterior and posterior at the same time and at the same level, with segmental cufflike extension of enhancing tissue around the dural sac. Stenosing tissue enhanced more frequently with rheumatoid arthritis than with degenerative disease (22 of 33 vs four of 16 patients, respectively; P =.008). CONCLUSION: In patients with rheumatoid arthritis, subaxial stenosis is frequently caused by enhancing epidural tissue. This enhancing tissue presumably represents pannus. | |
| 15005259 | An abrupt onset of seropositive polyarthritis with prominent distal tenosynovitis concomit | 2004 Feb | A 64-year-old Japanese woman with a two-week history of polyarthralgia and persistent cough was diagnosed as seropositive polyarthritis and fulfilled the criteria of early rheumatoid arthritis (RA). In addition, inflammatory pitting edema of the distal extremities was apparent, suggestive of the remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome. A number of investigations including hand MRI, bone scintigraphy and HLA typing supported a diagnosis of RS3PE syndrome rather than RA. Chest computed tomography revealed concomitant evidence of bronchiolitis obliterans organizing pneumonia (BOOP). Treatment with 30 mg of prednisolone daily immediately ameliorated the polyarthritis and the BOOP. Seropositive polyarthritis with distal pitting edema may be categorized as both RA and the RS3PE syndrome. | |
| 12510348 | [Novel autoantibodies and their target antigens in rheumatoid arthritis]. | 2002 Dec | Recently identified autoantibodies in rheumatoid arthritis are targeting autoantigen molecules, such as calpastatin, a novel form of soluble gp130, and follistatin-related protein, that appear to play a role in protecting effects in joint inflammation. These autoantibodies inhibit the function of target molecules and may be involved in the pathogenic mechanisms by upregulating inflammation and joint destruction. Another autoantibody targets filaggrin, a citullurinated protein distributed in keratinated epithelia. Although the pathogenic effect of anti-filaggrin antibody is not elucidated, this autoantibody has a potentiality of a new diagnostic marker of RA because of its high sensitivity and specificity. | |
| 12410460 | [Recurrence of Baker's cysts with regard to operation procedure and intraarticular patholo | 2002 Oct | During the period from January 1990 to December 1998 65 patients were operated upon for a Baker's cyst. 41 patients (43 operations) were subjected to a clinical and sonographical follow-up examination and interrogation. In 11 cases, the cysts were merely removed, while an open synovectomy was carried out four times (rheumatics) in addition to the removal of the cysts, and arthroscopy with exstirpation was performed in 28 cases. The total recurrence rate was 14 % (6/43). Any significant differences between the groups were not found (p = 0.291). The overall complication rate was 18.6 %. In case of recurrence, the clinical results were significantly worse (p = 0.036). Apart from technical aspects of operation, the not quantifiable correlation between grade of chondromalacia and the formation of effusions following joint degeneration has to be discussed as a cause for recurrences. If both interventions are carried out in one course, there is no increased operative risk. Especially in cases with intraarticular pathological symptoms arthroscopy should precede each cyst exstirpation. With regard to the frequency of recurrence, the patients' expectation should be preoperatively objectified. | |
| 11792878 | Rheumatoid Arthritis Severity Scale: a brief, physician-completed scale not confounded by | 2002 Jan | OBJECTIVE: The purpose of this study was to develop a brief measure of severity for rheumatoid arthritis (RA) that would not be seriously confounded by psychological functioning. The Rheumatoid Arthritis Severity Scale (RASS), designed for use by physicians on their own patients, consists of three visual analogue scales: Disease Activity, Functional Impairment and Physical Damage. METHODS: Ninety-four RA outpatients completed the Health Assessment Questionnaire (HAQ) Disability, Pain Severity, Health State subscales and the Symptom Checklist-90-Revised (SCL-90-R) Anxiety, Depression and Somatization subscales. Rheumatologists completed the RASS on their own patients. RESULTS: Results suggest that the RASS is internally consistent (alpha=0.85) and valid. RASS Disease Activity, Functional Impairment, Physical Damage correlated with HAQ Disability (r=0.40, 0.68, 0.61; P<0.01), Pain (r=0.37, 0.34, 0.34; P<0.01) and Health State (r=-0.27, -0.36, -0.27; P<0.01). RASS Physical Damage uniquely predicted longer illness duration (years with RA). In contrast to the HAQ, RASS subscales shared less variance with anxiety, somatization and depression scores. CONCLUSIONS: Preliminary data suggest that the RASS may be a quick, reliable, valid physician-completed RA severity scale that compares favourably with the longer, patient-completed HAQ. | |
| 11839562 | The co-expression of activating and inhibitory leukocyte immunoglobulin-like receptors in | 2002 Feb | Rheumatoid arthritis (RA) is a chronic inflammatory synovitis, with destruction of juxtaarticular cartilage and bone, likely mediated by lipid mediators, cytokines, and proteases released from inflammatory leukocytes. The mechanisms regulating leukocyte activation in rheumatoid synovium are not fully elucidated. A new family of cell surface proteins termed leukocyte immunoglobulin-like receptors (LIRs) has been shown in vitro to modulate cellular responses through immunoreceptor tyrosine-based inhibitory motifs or through association with the Fc receptor gamma chain that contains immunoreceptor tyrosine-based activation motifs. We studied the expression of inhibitory and activating LIRs in the synovium of six RA patients, three osteoarthritis patients, and three controls by immunohistochemistry. The synovium from patients with early RA showed extensive expression of the inhibitory LIR-2 and the activating LIR-7 on macrophages and neutrophils. Some mast cells and endothelial cells expressed LIR-7. There was limited expression of LIRs in synovium from two patients with long-standing RA, patients with osteoarthritis, and controls. LIR-2 recognizes MHC class I molecules. We therefore suggest that LIRs may regulate the activation of infiltrating leukocytes in synovial tissue and are a potential therapeutic target. | |
| 12196207 | B-lymphocyte depletion therapy in rheumatoid arthritis and other autoimmune disorders. | 2002 Aug | B-lymphocyte depletion therapy is being explored in a wide range of autoimmune disorders. In many, there is early evidence for efficacy, and immunosuppression has not been a major problem. The mechanism of action is unclear, but appears to be consistent with the lowering of autoantibody levels, where relevant antibodies are quantifiable. An interesting finding is the persistence of clinical improvement for periods of 1 year or more after B-lymphocyte return, which supports the concept that stochastic generation of rare pathogenic B-lymphocyte subsets may be a rate-limiting step in pathogenesis. | |
| 12794818 | The efficacy and safety of leflunomide in patients with active rheumatoid arthritis: a fiv | 2003 Jun | OBJECTIVE: To investigate the efficacy and safety of leflunomide beyond 2 years in a multinational, open-label extension of 2 phase III double-blind studies. METHODS: Patients with rheumatoid arthritis (RA) who received leflunomide (100 mg/day for 3 days, 10 mg/day or 20 mg/day thereafter) in the 2 phase III studies and who completed 2 years of treatment were offered inclusion in the open-label extension phase and were maintained on the same dosage of leflunomide. The American College of Rheumatology revised criteria for 20% improvement (ACR20), ACR50, and ACR70 response rates, the Stanford Health Assessment Questionnaire (HAQ) scores, and C-reactive protein (CRP) levels were assessed. Safety measures included monitoring of adverse events and laboratory values. RESULTS: A total of 214 patients (mean age 57 years) were treated with leflunomide for >2 years; 74.8% of the patients were female. The mean disease duration was 4.1 years (range 0.1-26.6 years), and in 44% of patients, RA was first diagnosed within 2 years of entry into the phase III studies. The mean duration of leflunomide treatment was 4.6 years (range 2.8-5.8 years), and 32% of patients had received no previous treatment with disease-modifying antirheumatic drugs. ACR20, ACR50, and ACR70 response rates and HAQ scores at 1 year were maintained through year 4 or until the end point. No new types of adverse events were observed, and liver function was normal at baseline and at the end point in the majority of patients. CONCLUSION: The improvements in both functional ability and physician-based efficacy measures seen with leflunomide after 1 year were maintained for up to 5 years (maximum treatment duration 5.8 years), demonstrating that the early efficacy of leflunomide in patients with RA is sustained long-term, and that the long-term safety profile of leflunomide is no different from that observed in phase III trials. | |
| 12632415 | A poly(ADP-ribose) polymerase haplotype spanning the promoter region confers susceptibilit | 2003 Mar | OBJECTIVE: To investigate the association of the poly(ADP-ribose) polymerase 1 (PARP-1) gene promoter polymorphism with rheumatoid arthritis (RA) predisposition. METHODS: An association study with 213 Spanish RA patients and 242 healthy subjects was carried out to investigate the association of all known PARP-1 gene promoter polymorphisms, i.e., a CA microsatellite repeat, a poly(A)(n), and 3 single point mutations (C410T, C1362T, and G1672A), with disease susceptibility. Additionally, we analyzed the distribution of PARP-1 polymorphisms in 58 Spanish families with 1 or more affected members. RESULTS: Upon complete genotyping of the panel of 455 samples, strong linkage disequilibrium was observed among the 5 PARP-1 polymorphisms. Only 2 PARP-1 haplotypes were detected: haplotype A (410T-[A](10)-[CA](10-12)-1362C, which includes short PARP-1 CA alleles) and haplotype B (410C-[A](11)-[CA](13-20)-1362T, always paired with long PARP-1 CA variants). Regarding the G1672A variation, although linkage disequilibrium was detected, it did not seem to be part of the conserved haplotypes described. Haplotype B was statistically overrepresented in the RA patient group compared with the healthy subjects (odds ratio 1.42, 95% confidence interval 1.06-1.91, P = 0.019). In addition, a significant dose effect of PARP-1 haplotype carriage on disease predisposition was observed. Of note, within haplotype B, the PARP-1 CA 97-bp allele was found to be the RA-predisposing marker (odds ratio 2.17, 95% confidence interval 1.27-3.72, P = 0.003, corrected P < 0.05). CONCLUSION: Our results demonstrate the existence of 2 unique PARP-1 haplotypes in the Spanish population and provide the first evidence that PARP-1 haplotypes play a role in susceptibility to RA. | |
| 12951306 | A new tool for rheumatology: large-scale analysis of gene expression. | 2003 Aug | Large-scale analysis of gene expression with cDNA arrays is spreading over many biological fields, including rheumatology. In this report, we wish to explain the principle and main advantages of this tool in the context of our discipline. Until 1995, analysis of gene expression was conducted for a few genes at a time but DNA chips now allow one to monitor the expression of thousands of genes in a single experiment and analyze the transcriptome, i.e. the whole of the transcripts in a given cell or tissue. Whatever the platform used (macro- or microarrays, oligo-chips), this technology rests upon the hybridization of i) a set of cDNA clones tethered to a solid support (nylon or glass) as probes, and ii) labelled cDNAs that are reverse-transcribed from bulk mRNAs extracted from a cell or tissue sample as a target. The end result is information on the relative abundance of every mRNA between two or more samples. The transcriptome analysis has two main objectives in rheumatology: i) identifying a gene expression profile that is a hallmark of a pathology and using it for a diagnostic or prognostic purpose, and ii) gathering genes with similar changes of expression, which allows one to specify the identity of novel proteins involved in a well-known intracellular cascade of regulation or even to identify new cascades. | |
| 15120170 | Multispectral analysis of bone lesions in the hands of patients with rheumatoid arthritis. | 2004 May | Quantitative measures of rheumatoid arthritis (RA) disease progression can provide valuable tools for evaluation of new treatments during clinical trials. In this study, a novel multispectral (MS) MRI analysis method is presented to quantify changes in bone lesion volume (DeltaBLV) in the hands of RA patients. Image registration and MS analysis were employed to identify MS tissue class transitions between two serial MRI exams. DeltaBLV was determined from MS class transitions between two time points. The following three classifiers were investigated: (a) multivariate Gaussian (MVG), (b) k-nearest neighbor (k-NN), and (c) K-means (KM). Unlike supervised classifiers (MVG, k-NN), KM, an unsupervised classifier, does not require labeled training data, resulting in potentially greater clinical utility. All MS estimates of DeltaBLV were linearly correlated (r(p)) with manual estimates. KM and k-NN estimates also exhibited a significant rank-order correlation (r(s)) with manual estimates. For KM, r(p) = 0.94 p < 0.0001, r(s) = 0.76 p = 0.002; for k-NN, r(p) = 0.86 p = 0.0001, r(s) = 0.69 p = 0.009; and for MVG, r(p) = 0.84 p = 0.0003, r(s) = 0.49 p = 0.09. Temporal classification rates were as follows: for KM, 90.1%; for MVG, 89.5%; and for k-NN, 86.7%. KM matched the performance of k-NN, offering strong potential for use in multicenter clinical trials. This study demonstrates that MS tissue class transitions provide a quantitative measure of DeltaBLV. | |
| 12022345 | Treatment with the angiogenesis inhibitor endostatin: a novel therapy in rheumatoid arthri | 2002 May | OBJECTIVE: An endostatin that inhibits angiogenesis dependent tumor growth is being tested as an antitumor agent. The neoangiogenesis condition of cancer is essentially identical to that of rheumatoid arthritis (RA). Thus antiangiogenic treatment has potential for treatment of RA. We investigated the effects of human recombinant endostatin on human RA synovial tissue by use of a novel model of RA, in which human RA tissue is grafted into SCID mice (SCID-HuRAg). METHODS: Ten or 50 mg/kg of human recombinant endostatin was administered by percutaneous direct intrasynovial injection in each of 7 SCID-HuRAg mice. We examined the volume of the grafted tissue mass and the histological changes 7 days after endostatin administration. Six control mice received phosphate buffered saline in the same manner. RESULTS: The grafted synovial volume of SCID-HuRAg mice was significantly decreased by endostatin administration. The number of inflammatory cells (macrophages and lymphocytes) was also significantly reduced in a dose dependent manner. The number of vessels that were counted by von Willebrand factor VIII and type IV collagen positive cells was decreased, although apoptotic cells were increased in RA synovia. CONCLUSION: The results suggest that antiangiogenesis treatment using endostatin represents a potential new therapeutic strategy for RA. | |
| 14967082 | Cricoarytenoiditis in rheumatoid arthritis: radiologic and clinical study. | 2003 Dec | The cricoarytenoid (CA) joint involvement in rheumatoid arthritis (RA) is not uncommon. In this study, clinical assessment, laryngeal endoscopy, and high-resolution computed tomography (HRCT) were used in 15 patients with RA to evaluate the diagnostic criteria of CA joint involvement. Symptoms owing to CA joint involvement were present in 66.6% of the patients. The frequency of involvement was 13.3% on laryngeal endoscopy but 80.0% with HRCT assessment. The most common HRCT findings were CA prominence (46.6%), density and volume changes (46.6%), and CA subluxation (39.9%). In some of the patients, soft tissue swelling (20%) near the CA joint and narrowing in the piriform sinus (33.3%) were also observed. Radiologic abnormalities related to CA joint involvement generally precede clinical symptomatology. Therefore, HRCT evaluation may be a useful method in the assessment of CA joint involvement in RA patients to exclude possible causes of laryngeal signs and symptoms. | |
| 15656036 | Myelodysplasia and acute myeloid leukaemia in a case of rheumatoid arthritis with secondar | 2004 May | Immunosuppressive therapy related secondary haematologic malignancy is well reported. A 52 years lady with established rheumatoid arthritis developed reactive amyloidosis. This was initially treated with colchicine and cyclophosphamide and later with chlorambucil. Ten months after stopping chlorambucil she developed pancytopenia and vitamin B12 deficient megaloblastic anaemia. The pancytopenia was refractory to vitamin B12 supplements and a repeat bone marrow confirmed myelodysplasia (FABI RAEB-T). Within three weeks of this diagnosis she evolved into acute myeloid leukaemia and expired due to refractory thrombocytopenia and uncontrolled bleeding. This case stresses the need for long term follow up of RA patients treated with alkylating agents. | |
| 12780697 | Release of endogenous anti-inflammatory complement regulators FHL-1 and factor H protects | 2003 Jun | Rheumatoid arthritis is a chronic inflammatory disease of unknown aetiology predominantly affecting cells and tissues of synovial joints. Here we show that the two important complement regulators FHL-1 and factor H play a protective anti-inflammatory role in rheumatoid arthritis. Expression analyses at the mRNA- and protein level show in vitro expression and secretion of both regulators by synovial fibroblasts derived from patients with rheumatoid arthritis. Similarly the two regulators are synthesized in vivo in diseased synovial tissue, and in particular synovial lining cells express high levels of FHL-1. The anti-inflammatory role of these regulators in rheumatoid arthritis is highlighted by their induction with IFN-gamma and dexamethasone, whilst the pro-inflammatory cytokine TNF-alpha had no effect. Transient transfection experiments with various FHL-1/factor H promoter-luciferase reporter constructs into cells of distinct origin show independent cell and tissue specific promoter regulated transcription of these two regulators. The inducible expression, specifically of FHL-1 has physiological consequences. By binding directly to surfaces the released proteins protect cells from inflammatory damage and complement-mediated cell lysis. This study shows a novel protective and anti-inflammatory role of the two important complement regulators FHL-1 and factor H in rheumatoid arthritis and suggests a disease controlling role of the two proteins. | |
| 15554366 | [Standardisation proposal for monitoring rheumatoid arthritis patients in Croatia]. | 2004 | Monitoring of outcome measures is carried out because of the assessment of medical care quality, also in scientific researches i.e. clinical trials. However, it is rarely carried out in daily clinical practice due to lack of time. Our goal was to choose the outcome measures set for monitoring disease activity in rheumatoid arthritis (RA) which encompasses validity, reliability and sensitivity and also primarily satisfies feasybility criteria in daily clinical practice. We have analyzed the following parametres in 83 unselected patients with RA diagnosis in our department: the mutual relation of single measures of the disease activity (Ritchie index, number of swollen joints, general health status assessment with VAS and SE), their relation to the DAS and HAQ and the relation between the DAS and HAQ. We have recently replaced the Ritchie index by 28DAS, and HAQ by mHAQ. The values of correlation between the single measures of the disease activity which we had found out by statistical processing justify their usage in assessment of the clinical status, however the non-existence of the correlations compared to HAQ points to unreliability when used in evaluation of the disease activity. Unlike the single measures, DAS has positive correlation compared to HAQ. Based on our experience in past two years and recommendations found in literature, we suggest introducing the outcome measures set for monitoring disease activity in rheumatoid arthritis in clinical care. That would be mHAQ as the long-term outcome in measuring the disease activity and parametres by which DAS28 (number of tender joints, number of swollen joints, general health status assessment by VAS, SE) can be calculated as short-term outcome. | |
| 15379777 | Adalimumab: efficacy and safety in psoriasis and rheumatoid arthritis. | 2004 | The next generation of targeted biologic therapies for psoriasis will either be directed against new protein targets or improve on the efficacy, safety, or convenience of medications available for an already validated area in the immune response. Adalimumab is a fully human monoclonal antibody directed against tumor necrosis factor-alpha, a central cytokine in the immune response in psoriasis that has already been shown to be an effective target for therapy. This medication is approved by the US Food and Drug Administration (USFDA) for the treatment of rheumatoid arthritis. Early phrase II studies with adalimumab have shown excellent efficacy for psoriasis with either weekly or every other week subcutaneous injection. Moreover, the safety and tolerability of adalimumab in large clinical studies of rheumatoid arthritis have shown good results. Thus, adalimumab shows significant promise for the therapy of psoriasis in the future. |
