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Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
12111401 Involvement of apoptotic cell death in autoimmune diseases. 2002 Mar A low rate of as well as a high rate of apoptotic cell death is involved in the development of various human autoimmune diseases. In rheumatoid arthritis (RA), impaired apoptosis of rheumatoid synovial cells appears to induce hyperplasia of the synovial tissues, whereas the acceleration of apoptotic cell death of osteoblasts may contribute to periarticular bone loss in patients with RA. Humoral factors including cytokines and growth factors present in the rheumatoid synovial tissues modulate the expression of apoptosis-related molecules in the cells, which inhibits or stimulates the apoptotic process of synovial cells and osteoblasts. In addition, investigations of animal arthritis models suggest that an enforced induction of apoptotic cell death of synovial cells ameliorates synovial tissue hyperplasia. The increase of salivary gland cell apoptosis and the resistance of apoptotic cell death in salivary infiltrating mononuclear cells have been observed in patients with Sjögren's syndrome (SS). Immunohistochemical studies indicate that X chromosome linked inhibitor of apoptosis protein in salivary gland cells as well as Bcl-2/Bcl-xL in salivary infiltrating mononuclear cells may be critical anti-apoptogenic molecules in each cell type. Human T-lymphotropic virus type I (HTL V-I) is one of the pathogenic organisms for RA and SS, and we demonstrated that HTL V-I tax stimulates NF-kappa B nuclear translocation, inhibiting apoptotic cell death of human host cells, which may accelerate the autoimmune process. The association between the apoptosis of thyrocytes and the process of autoimmune thyroid diseases has also been examined, and our data suggest that Fas-mediated apoptosis of human thyrocytes is modulated by thyroid-stimulating antibodies, thyroid stimulation blocking antibodies, and cytokines. These data indicate that the correction of apoptotic cell death in each cell type will become a new therapeutic strategy for treatment of human autoimmune diseases.
12935785 Evaluation of differentially expressed genes by a combination of cDNA array and RAP-PCR us 2003 Sep Evaluation of genes regulated differentially is essential for the development of therapeutic approaches in multifactorial diseases. To characterize gene expression profiles in multifactorial inflammatory and malignant diseases such as rheumatoid arthritis (RA) or colon adenoma (CA), RNA arbitrarily primed PCR (RAP-PCR) combined with cDNA array hybridization were performed and evaluated using an array-specific software.RNA of synovial fibroblasts from patients with RA and osteoarthritis (OA), and laser microdissected normal and colon adenoma tissue was used. RAP-PCR reactions were hybridized to cDNA array membranes. Arrays were analyzed by phosphor imaging, and the AtlasImage 2.0 software with different normalization settings. The AtlasImage 2.0 software was a useful tool to evaluate differentially expressed genes. However, software settings were needed to be optimized for every experimental approach and should be used without changes for all experiments. To compare RA vs. OA synovial fibroblasts and normal vs. CA expression patterns, global normalization using the sum method is recommended.
12223314 Use of complement inhibitors in tissue injury. 2002 Sep A great deal of information has accumulated implicating the complement system in several human disease processes. Although some of this information is circumstantial, protein inhibitors of the complement system have been developed and applied successfully to experimental disease models in animals. Two inhibitors, soluble complement receptor 1 (sCR1) and anti-C5 monoclonal antibody, are now being investigated in a variety of clinical conditions such as systemic lupus erythematosus and rheumatoid arthritis (RA), diseases for which current therapy has changed little and remains unsatisfactory. Preliminary successes in Phase II clinical trials of RA have provided optimism that complement inhibition might prove useful in these diseases and become part of standard medical therapy.
12847677 Association of the -2849 interleukin-10 promoter polymorphism with autoantibody production 2003 Jul OBJECTIVE: To analyze the -2849 A/G interleukin-10 (IL-10) promoter polymorphism, which is associated with high (AG/GG) and low (AA) IL-10 production, in a cohort of rheumatoid arthritis (RA) patients and controls in order to gain a better understanding of its role in the incidence and progression of RA. METHODS: Allele frequencies of the promoter polymorphism -2849 A/G and carriage rates were compared in 283 RA patients, 413 patients with other rheumatic diseases, and 1,220 healthy controls. The rate of joint damage and baseline levels of IgG and IgM rheumatoid factors and anti-citrullinated peptide antibodies were measured and were correlated with the IL-10 gene polymorphism. Furthermore, the correlation between the invasiveness of fibroblast-like synoviocytes (FLS) and the -2849 IL-10 genotype was tested. RESULTS: The IL-10 genotype was not associated with the incidence of RA, but instead, correlated with disease progression, as determined by the extent of joint destruction. A higher rate of joint destruction was observed in patients with the genotype associated with high IL-10 production. Since FLS are thought to be involved in joint destruction, we analyzed IL-10 genotypes in conjunction with FLS invasiveness. Although adenoviral gene transfer of IL-10 to FLS inhibited their invasiveness, no differences were observed in vitro in the FLS from RA patients who were -2849 non-G carriers compared with those who were G carriers. Instead, patients with the -2849 AG/GG genotype, which is associated with high IL-10 production, had higher autoantibody titers at baseline. CONCLUSION: The -2849 IL-10 promoter polymorphism is associated with autoantibody production and subsequent joint damage in RA.
15319232 Silica exposure is associated with increased risk of developing rheumatoid arthritis: resu 2005 Apr OBJECTIVE: To study the association between silica exposure and rheumatoid arthritis and how it is modified by cigarette smoking. METHODS: Data were analysed from 276 male cases and 276 male controls aged 18 to 70 years, included in a Swedish population based study between May 1996 and June 2001. A case was defined as a person recently diagnosed with rheumatoid arthritis according to the ACR criteria. Controls were selected from the study base as a stratified random sample accounting for age, sex, and residency. Men with a self reported history of work with rock drilling, stone crushing, or exposure to stone dust in general were defined as silica exposed. Rheumatoid factor (RF) status among cases was recorded. RESULTS: Silica exposed men had increased risk of rheumatoid arthritis, with an odds ratio (OR), adjusted for age, residential area, and smoking, of 2.2 (95% confidence interval, 1.2 to 3.9) among men aged 18 to 70 years, and 2.7 (1.2 to 5.8) among those aged 50 to 70 years. Men who had worked with rock drilling or stone crushing (regarded as highly exposed) had a slightly greater increase in risk of rheumatoid arthritis than silica exposed men in general, with an OR of 3.0 (1.2 to 7.6). The joint effects of silica exposure and smoking were compatible with synergy between these two exposures in the development of rheumatoid arthritis but this was not conclusive. CONCLUSIONS: Silica exposure is associated with increased risk of developing rheumatoid arthritis. This association is not explained by smoking habits.
15020336 Evaluation of anti-citrullinated filaggrin antibodies as hallmarks for the diagnosis of rh 2004 Apr BACKGROUND: Anti-filaggrin antibodies (AFA) are among the most specific antibodies for rheumatoid arthritis, so procedures for their detection should be included in early biological diagnoses. AFA can be detected by indirect immunofluorescence (anti-keratin antibodies, AKA) or by new enzyme immunoassays (EIA). Their comparative performance needs to be established. OBJECTIVE: To compare these technical procedures to optimise the serological diagnosis of rheumatoid arthritis. METHODS: Results obtained using AKA and EIA were compared in 271 sera from 140 patients with rheumatoid arthritis at various stages, 98 patients with other autoimmune diseases, and 33 healthy subjects. EIA were successively undertaken with citrullinated linear filaggrin peptide (home made EIA) or cyclic citrullinated peptide (CCP2, commercial kits). Rheumatoid factor (RF) was assessed by EIA in all patients. RESULTS: Anti-CCP2 kits showed the best sensitivity and specificity (65% and 96%, respectively). Among the 140 patients with rheumatoid arthritis, those with very recent disease (less than six months' duration, n = 21) were studied as a separate group. In this group, the sensitivity of anti-CCP2 kits decreased to approximately 50%. Nevertheless this assay remained the most accurate when compared with AKA or home made EIA using linear filaggrin peptides. The combination of anti-CCP2 and RF only slightly increased the sensitivity of the diagnosis of very early rheumatoid arthritis. CONCLUSIONS: Kits using citrullinated cyclic peptides (CCP2) were more suitable than either AKA or EIA using linear filaggrin peptides for the diagnosis of early rheumatoid disease.
11824968 Expression and localization of vascular endothelial growth factor-C in rheumatoid arthriti 2002 Jan OBJECTIVE: Vascular endothelial growth factor-C (VEGF-C), a member of the VEGF family, induces lymphangiogenesis through VEGF receptor-3 (VEGFR-3/Flt-4). We examined the expression and localization of VEGF-C to clarify its role in synovial tissues in rheumatoid arthritis (RA). METHODS: Reverse transcription-polymerase chain reaction (RT-PCR), Western blot analysis, immunohistochemical staining, and in situ hybridization for VEGF-C were performed on synovial tissue specimens obtained from 10 patients with RA and 4 with osteoarthritis (OA). VEGFR-3 expression was determined using Western blot analysis. RESULTS: RT-PCR analysis showed that VEGF-C mRNA was expressed in all RA and OA synovial tissues. Based on Western blot analysis, the mature form of VEGF-C was found in RA synovial tissues, but not in OA synovial tissues, and VEGFR-3 was detected in RA and OA synovial tissues. Immunohistochemical staining showed that the VEGF-C protein was localized in many synovial lining cells, endothelial cells, and stromal cells in RA synovial tissues. In OA synovial tissues, the VEGF-C protein was localized in synovial lining cells and endothelial cells. A large number of synovial lining cells and stromal cells surrounding microvessels in RA synovial tissues expressed VEGF-C mRNA, as determined by in situ hybridization. CONCLUSION: Mature VEGF-C and VEGFR-3 expression may contribute to lymphangiogenesis in RA.
14668927 Objectives and strategies for rheumatoid arthritis therapy: yesterday vs. today. 2003 The goals for the treatment of rheumatoid arthritis have changed from slowing the disease process only after a definitive diagnosis is made, to intervening early to minimize disease activity and achieve and maintain remission. To meet the new goals, both monotherapy and combination therapy must be administered not only early but aggressively, and aggressive therapy must be sustained. In addition, the efficacy of this treatment design can only be achieved if disease activity is monitored.
12814762 Cross-cultural adaptation and validation of an Arabic Health Assessment Questionnaire for 2003 Jun OBJECTIVE: To test the reliability and validity of a modified and translated version of the original Health Assessment Questionnaire (HAQ) on patients with rheumatoid arthritis (RA). METHOD: A cohort of 184 RA patients from different Arabic countries (Egypt, Saudi Arabia, Sudan, Syria, Bahrain, Kuwait and Morocco) were recruited and asked to participate in the study. Two questions had been changed to suit the Arabic culture and to tackle some aspects that are commoner to be performed in the Arabic culture. After modification, translation and retranslation of the questionnaire, it was administered to the selected patients and tested for internal consistency, reliability and construct validity by correlating the yield of the questionnaire with other disease activity parameters. The questionnaire was administered again after a 1-week interval for evaluation of the reliability of this test. The modified questions were tested for their loyalty to the principal component and comparing their correlation with that of the other unchanged items. RESULTS: Test-retest showed strong reliability with a high percentage of agreement and high values for Kappa. Internal consistency showed a high value for standardized alpha (Cronbach's): 0.979 that did not show any significant change if any of the 20 items had been eliminated. The modified questionnaire had shown a strong validity when correlating its results with other disease activity parameters. This correlation was the strongest with tender joint count (TJC), Ritchie articular index (RAI), morning stiffness (MS) and visual analogue scale (VAS) and the least (but still significant) with rheumatoid factor (RF). CONCLUSION: The Arabic HAQ is a reliable and valid instrument that can be self-administered to Arabic RA patients to evaluate their functional disability. Its measurement properties were comparable to versions in other languages.
15180892 Safety of rituximab in the treatment of B cell malignancies: implications for rheumatoid a 2003 The chimeric anti-CD20 monoclonal antibody rituximab has been used extensively in the treatment of B cell malignancies, and more recently it has emerged as a potential treatment for rheumatoid arthritis (RA), via selective B lymphocyte depletion. Experience in oncology shows that rituximab is well tolerated in a variety of settings, with mild-to-moderate infusion related reactions following the first infusion being the most common adverse event. Current data suggest that the safety profile of rituximab in patients with RA is similar to that in oncology, but that the adverse events are less frequent and less severe in patients with RA.
15020338 Dose escalation of infliximab in clinical practice: improvements seen may be explained by 2004 Apr OBJECTIVE: To determine whether increased infliximab doses result in better clinical outcome in rheumatic diseases. METHODS: Subjects were 124 patients with rheumatoid arthritis treated with biological agents at a single institute. Index cases were 44 patients whose infliximab doses had been increased. Controls were patients treated with infliximab without dose increase (n = 44), and patients treated with etanercept (n = 36). Disease activity score (DAS28), ACR28 swollen joint counts, and numerical ACR responses were compared before and after dose increases. For the controls, the point at which the DAS28 value showed any increase (despite infliximab/etanercept treatment) was used as the reference time point. Comparisons were made between three sets of outcomes: best outcome achieved before the dose increase (cases) or before the reference time point (controls); outcomes at this point; and best outcomes after this point. RESULTS: Following dose increase, disease activity showed modest but statistically significant improvements. The improvement achieved after dosage escalation was equal to, but not better than, the best values before dose escalation. While this finding could be interpreted as "recapturing" the previous response, similar improvements were seen in both control groups. Thus the same pattern of worsening and subsequent improvement was seen with or without the infliximab dose increase. CONCLUSIONS: Clinical improvement with increased infliximab dose, and the impression that a previous response can be "recaptured" with higher doses, cannot be taken at face value, as similar improvements occurred in two control groups. The use of infliximab at doses higher than 3 mg/kg needs to be evaluated further.
11989298 [Multivariate analysis of factors influencing the effect of radiosynovectomy]. 2002 Apr OBJECTIVE: In this prospective study, the time to remission after Radiosynovectomy (RSV) was analyzed and the influence of age, sex, underlying disease, type of joint, and duration of illness on the success rate of RSV was determined. METHODS: A total number of 57 patients with rheumatoid arthritis (n = 33) and arthrosis (n = 21) with a total number of 130 treated joints (36 knee, 66 small and 28 medium-size joints) were monitored using visual analogue scales (VAS) from one week before RSV up to four to six months after RSV. The patients had to answer 3 times daily for pain intensity of the treated joint. The time until remission was determined according to the Kaplan-Meier survivorship function. The influence of the prognosis parameters on outcome of RSV was determined by multivariate discriminant analysis. RESULTS: After six months, the probability of pain relief of more than 20% amounted to 78% and was significantly dependent on the age of the patient (p = 0.02) and the duration of illness (p = 0.05), however not on sex (p = 0.17), underlying disease (p = 0.23), and type of joint (p = 0.69). CONCLUSION: Irrespective of sex, type of joint and underlying disease, a measurable pain relief can be achieved with RSV in 78% of the patients with synovitis, whereby effectiveness is decreasing with increasing age and progress of illness.
12945645 Evaluation of wrist and hand handicap and postoperative outcome in rheumatoid arthritis. 2003 Aug Functional instruments in rheumatology should use standardized procedures and should be quantifiable, valid, reliable, and responsive/sensitive to change. For most assessment tools, these aspects have been considered and tested. One of the most important questions in assessing hand involvement in patients with RA is what the single assessment should be used for. There could be a substantial difference should hand assessment be done in a routine way in a hand practice or should it be performed within scientific studies on disease progression or the effect of operative interventions. Among other points, answering this question has a significant impact on the time the patient has to spend with the tests and on the time the hand therapist or hand surgeon is involved with it. In addition to aspects such as accuracy, reliability, and validity, therefore, in some evaluation tools the time needed to perform the clinical examination and assessment of hand function has also been considered to be of importance. In addition, it has to be considered that description of the anatomic status, measurements of impairment, and assessment of disability cannot simply be replaced by each other, and even measurements of single aspects often are not sufficient. It has been stated, therefore, that the combination of different discrete hand-function assessment methods provides a more complete picture of hand ability. Moreover, although better responsiveness of disability outcome measures over impairment measures has been demonstrated previously (eg, in patients treated for Colle fracture), the relationship between disability and impairment measures is not clearly established. Although some studies reported significant correlations between impairment and disability tests, other studies showed only poor or moderate correlations between disability scores, impairment, and disease activity measures when rheumatoid hands were assessed. It has been concluded that the relationship between impairment and disability is not straightforward. The new ICF-model addresses these two levels of health-related quality of life by different concepts of assessment. Because impairment reflects the consequences of the disease at the organ level, whereas disability reflects the consequences of the disease for functional performance and activity, for comprehensive assessment of hand handicap, measurement of disability is more comprehensive and closer to the patient's needs for performing ADLs.
11829337 Arthroscopic treatment of synovial disorders in the shoulder, elbow, and ankle. 2002 Winter A wide range of synovial conditions can affect patient function and often respond to conservative treatment. However, when symptoms do not respond, arthroscopic synovectomy is a useful tool for management. Pigmented villonodular synovitis, synovial chondromatosis, rheumatoid arthritis, adhesive capsulitis of the shoulder, and ankle impingement are the diseases that most often require synovectomy. Arthroscopic management offers the following advantages over open synovectomy: a more thorough evaluation of the joint and synovium, better access for surgical synovectomy, and decreased postoperative morbidity.
15022314 Tumor necrosis factor receptor II gene polymorphism and severity of rheumatoid arthritis. 2004 Mar OBJECTIVE: The gene encoding tumor necrosis factor receptor type II (TNFRII) is a strong candidate in the pathogenesis of rheumatoid arthritis (RA). An association between a single-nucleotide polymorphism (196M/R) in exon 6 of the TNFRII gene and familial RA was recently reported. The present study was undertaken to test the hypothesis that there is an association between this polymorphism and the severity of RA. METHODS: One hundred two white patients with early RA were included in this prospective study. The French version of the Health Assessment Questionnaire (F-HAQ) and a radiographic damage score (modified Sharp/van der Heijde method) were used to quantify the functional and structural severity of RA at baseline and after 4 years of followup. TNFRII 196M/R polymorphism genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism analysis. RESULTS: Among the 102 patients with RA, 63 (61.8%) were homozygous for the 196M allele, 36 (35.3%) were heterozygous for alleles 196M and 196R, and 3 (2.9%) were homozygous for the 196R allele. At baseline, the median radiographic and F-HAQ scores did not differ between RA patients who carried the 196R allele and those who did not. After 4 years of followup, the F-HAQ score was higher in RA patients carrying the 196R allele (median 1 [interquartile range (IQR) 0.125, 1.375]) than in noncarriers (0.375 [IQR 0, 1]) (P = 0.02), while the median radiographic score did not differ between RA patients who carried the 196R allele and those who did not. CONCLUSION: The results of the present study support the hypothesis that there is an association between the TNFRII 196 M/R gene polymorphism and the functional severity of early RA.
15067318 Experimental arthritis in CC chemokine receptor 2-null mice closely mimics severe human rh 2004 Mar The prevailing paradigm is that in human rheumatoid arthritis (RA), the accumulation of monocytes and T cells in the joint, mediated in part by such CC chemokine receptors (CCRs) as CCR2 and CCR5, respectively, plays a central role in disease pathogenesis. To further validate this paradigm, we conducted proof-of-principle studies and tested the hypothesis that gene inactivation of Ccr2 or Ccr5 will ameliorate experimental RA. Contrary to our expectations, we found that in two well-established murine models of experimental RA, CCR2 expression in the hematopoietic cell compartment served as a negative regulator of autoantibody production as well as arthritic disease onset, severity, and resolution. In contrast, the RA phenotype in Ccr5-null mice was similar to that of WT mice. Remarkably, the collagen-induced arthritis phenotype of Ccr2-/- mice mimicked closely that of severe human RA, including production of rheumatoid factor, enhanced T cell production, and monocyte/macrophage accumulation in the joints. Our findings demonstrate an essential protective role of CCR2 expression in RA, indicate the existence of alternative receptors responsible for monocyte/macrophage accumulation to inflamed joints, and emphasize the need to clarify carefully the complex effects of the chemokine system in RA before they can be considered as therapeutic targets.
12510352 [Cross-talk between immune and skeletal systems]. 2002 Dec Bone destruction in rheumatoid arthritis is characterized as 'the defective control of bone metabolism by the immune system'. During the course of our study to investigate the mechanism of arthritic bone destruction, we have explored a new field called' osteo-immunology'. Here we summarize the regulation of the bone metabolism by signalling cross-talk between RANKL and IFNs, focusing on the T cell-mediated regulation of osteoclastogenesis by IFN-gamma. The better understanding of the interactions between bone and immune cells will provide further insights into the both fields.
11795701 Use of a titanium mesh cage for posterior atlantoaxial arthrodesis. Technical note. 2002 Jan The authors placed titanium mesh cages to achieve posterior atlantoaxial fixation in five patients with atlantoaxial instability caused by rheumatoid arthritis or os odontoideum. A mesh cage packed with autologous cancellous bone was placed between the C-1 posterior arch and the C-2 lamina and was tightly connected with titanium wires. Combined with the use of transarticular screws, this procedure provided very rigid fixation. Solid fusion was achieved in all patients without major complications. The advantages of this method include more stable fixation, better control of the atlantoaxial fixation angle, and reduced donor-site morbidity compared with a conventional atlantoaxial arthrodesis in which an autologous iliac crest graft is used.
15478161 Patient-reported health care utilization in rheumatoid arthritis: what level of detail is 2004 Oct 15 OBJECTIVE: To investigate the level of detail required in self-reported health care utilization questionnaires for administration to patients with rheumatoid arthritis (RA). METHODS: A preliminary questionnaire was developed on the basis of existing tools for use in rheumatic conditions and in-depth interviews with 10 RA patients. Data gathered over 1 year of administration in a clinical setting were then matched to a comprehensive database of payer-reported information. Kappa statistics were calculated for each health care utilization domain. For domains where disaggregation into metric data was potentially preferable, histograms of difference were assessed visually and the strength of association examined using Spearman's rank correlation coefficient. RESULTS: Patients (n = 136) included in the base case analysis determined the preferred levels of detail for each domain. Physician visits: occurrence of physician visits (yes/no; kappa not applicable) and their number (r = 0.42, P < 0.001). Medication use of the following drug classes (yes/no): disease-modifying antirheumatic drug (DMARD; kappa = 0.68), nonsteroidal antiinflammatory drug (kappa = 0.64), osteoporosis medication (kappa = 0.56), analgesic (kappa = 0.38), and steroid (kappa = 0.83). Further disaggregation into different DMARD classes was recommended (kappa ranging between 1 [use of biologics: yes/no] and 0.67 [use of azathioprine: yes/no]. Imaging: imaging of bones and chest (yes/no; kappa = 0.20). Hospitalization: inpatient episodes (yes/no; kappa = 0.64) and number of inpatient days (r = 0.80, P < 0.001). Transport: costs incurred (yes/no; kappa = 0.13) and amount (r = 0.39, P < 0.001). CONCLUSION: The use of highly aggregated items to assess health care utilization in RA is supported. Dichotomous assessment (yes/no) was the preferred level of detail for items in the domains covering medication and diagnostic procedures or tests. Metric data is appropriate in 3 areas: number of physician visits, number of inpatient days, and total expenditure on transportation.
12669994 Classification of rheumatoid joint inflammation based on laser imaging. 2003 Mar We describe a classification system for a novel imaging method for arthritic finger joints. The basis of this system is a laser imaging technique which is sensitive to the optical characteristics of finger joint tissue. From the laser images acquired at baseline and follow-up, finger joints can automatically be classified according to whether the inflammatory status has improved or worsened. To perform the classification task, various linear and kernel-based systems were implemented and their performances were compared. Based on the results presented in this paper, we conclude that the laser-based imaging permits a reliable classification of pathological finger joints, making it a sensitive method for detecting arthritic changes.