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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
9972956 Radiologic progression in early rheumatoid arthritis treated with methotrexate. 1999 Feb OBJECTIVE: To evaluate radiologic progression in patients with early rheumatoid arthritis (RA) receiving methotrexate (MTX) as the first slow acting drug. METHODS: An open, prospective study of 29 patients with RA (21 F, 8 M, mean age 48.5+/-15.4 yrs). The mean duration of RA was 6.6 (2-60) months; and rheumatoid factor was present in 11 cases. Clinical, biological, and radiographic evaluations were done before the start of MTX treatment and after 13+/-3.8 months. Radiographs of hands and wrists were blindly studied by 2 physicians, using Larsen's and modified Sharp's methods. There was a significant correlation for the scores of the 2 physicians evaluated by kappa coefficient. Radiographic evolution was defined as an increase of 15 points in the radiologic score by each method used. RESULTS: Patients showed significant clinical improvement after one year of MTX treatment. Despite clinical and biological improvement, significant mean radiographic progression was noted, with Larsen's method (p = 0.001) and Sharp's method (p = 0.034), without reaching the maximum score. However, using the definition of radiographic progression, the radiologic scores indicated stabilization in 23 patients with Larsen's method and in 24 patients with Sharp's method. CONCLUSION: This study revealed mild radiographic progression in early RA patients treated with MTX for one year. Further controlled studies are needed.
10036637 Human parvovirus B19 in rheumatoid arthritis. 1998 Viral arthritis occurs transiently in most cases, because the infection is self limiting. The arthropathy associated with human parvovirus B19, however, often lasts for more than 2 years and their clinical symptoms may resemble with those of rheumatoid arthritis. Data have been accumulating for the link of B19 infection with chronic polyarthropathy or rheumatoid arthritis (RA), and we discuss the possible mechanism for the role of B19 in the etiopathology of RA.
10090159 Prognostic factors for the development of rheumatoid arthritis and other connective tissue 1999 Mar OBJECTIVE: Palindromic rheumatism is characterized by attacks of acute arthritis of short duration. In the long term, a substantial proportion of patients will develop rheumatoid arthritis (RA) or other connective tissue diseases, but the determinants of subsequent chronic disease have not been adequately established. We identify clinical prognostic factors for the development of RA and other connective tissue diseases in patients with palindromic rheumatism in a retrospective cohort study. METHODS: The medical records of 4900 patients with arthritis referred from 1986 to 1996 to 3 rheumatologists at an academic center were reviewed. One hundred sixty patients were diagnosed as having palindromic rheumatism. After review, 127 complied with diagnostic criteria for palindromic rheumatism. Disease duration was estimated as time of first attack until the last consultation, or the development of RA or other connective tissue disease. Survival analysis including Cox regression was used to identify clinical variables associated with the risk of developing RA or other connective tissue disease, adjusting for varying disease duration. RESULTS: Sixty-five percent of the patients were female. Age at onset was 40+/-12 years. Mean disease duration was 6+/-6 years, and mean followup by the rheumatologists was 40+/-45 months. Joints more frequently affected were wrist, knee, and metacarpophalangeal. Forty-three patients (34%) subsequently developed a connective tissue disease including 36 (28%) RA, 3 (2%) systemic lupus erythematosus, and 4 (3%) other connective tissue diseases. In the final Cox regression model the hazard ratio for development of a connective tissue disease in the presence of a positive rheumatoid factor (RF) was 2.9 (p = 0.002), for proximal interphalangeal (PIP) joint involvement 2.4 (p = 0.02), for wrist involvement 2.5 (p = 0.05), for female sex 2.2 (p = 0.05), and for age at onset 1.03 (per year) (p = 0.001). Female patients with positive RF and involvement of the hands had an 8-fold risk of developing disease, compared with patients with one or fewer of these features. CONCLUSION: Positive RF and early involvement of the wrist and PIP joints predict the subsequent development of RA or other connective tissue disease in patients with palindromic rheumatism, and identify a group of patients at increased risk.
10321961 HLA DRB1, DMA, and DMB gene polymorphisms in rheumatoid arthritis. 1999 Mar OBJECTIVE: To study the influence of DMA and DMB genes on susceptibility to Rheumatoid Arthritis (RA). METHODS: HLA-DRB1, DMA and DMB polymorphisms were defined by PCR SSOP in 203 European Mediterranean RA patients and 181 unrelated healthy controls. RESULTS: No significant difference in the phenotype frequencies of DMA and DMB alleles was observed between patients and controls. We found decreased frequencies of DMA*0102 and DMB*0104 in patients but this did not reach significance. These decreased frequencies could be due to a positive linkage disequilibrium with DRB1*0701, an allele which is underrepresented in RA patients. In stratified analysis with RA susceptibility Epitope positive (SE) DRB1 alleles, there was no significant difference in DMA and DMB phenotype frequencies between SE/SE, SE/X, and X/X patients versus controls. Among SE/X subjects, no significant difference in DM distribution frequencies was observed in DRB1*0101/X, 0102/X, 0401/X, 0404/X and 0405/X groups. CONCLUSION: DMA and DMB polymorphism does not seem to influence susceptibility to develop RA. Differences in DMA phenotype frequencies between patients and controls are secondary to linkage disequilibrium with DRB1 alleles.
11093596 Diet therapy for rheumatoid arthritis. A controlled double-blind study of two different di 2000 OBJECTIVE: To evaluate the effects of a diet therapy in patients with rheumatoid arthritis (RA). METHODS: Fifty RA patients entered a 24-week double-blind, randomised, controlled-study of two different dietary regimens (an experimental diet high in unsaturated fats, low in saturated fats with hypoallergenic foods vs. a control well-balanced diet). The primary end points of the study were 20% and 50% improvement in disease activity according to composite symptoms (Paulus index) of arthritis. Other end points were the other measures of disease activity at 12 and 24 weeks of diet treatment. RESULTS: The 2 groups were comparable at inclusion. Diet treatment was well tolerated and the rate of drop-outs was low. Percentage of patients with global 20 or 50% response didn't differ between experimental and control group after the 24-week of diet treatment. The experimental diet group did better for all the variables considered but only four variables (Ritchie's index, tender and swollen joints, and ESR) reached a statistical difference by multivariate analysis. Adjusting these data for weight variations, the number of tender joints (p=0.014) and ESR (p=0.025) were still statistically significant. CONCLUSIONS: Dietary manipulation, either by modifying food supplements or by reducing weight, may give some clinical benefit although no significant improvement can be observed assessing the results with a composite index.
11642498 Autologous stem cell transplantation for rheumatoid arthritis--interim report of 6 patient 2001 Oct We assessed the safety and efficacy of autologous stem cell transplantation (ASCT) using T cell depleted grafts in the treatment of severe rheumatoid arthritis. Methods included mobilization 2 g/m2 cyclophosphamide (Cy) and granulocyte-colony stimulating factor; graft manipulation of positive CD34+ and negative T cell selection; and conditioning by 200 mg/kg Cy. All 6 patients improved according to American College of Rheumatology response criteria (one patient ACR70, 2 ACR50, 3 ACR20), but relapsed at 1.5-9 months when they began cyclosporine A (CSA). Five improved (one patient ACR remission, 2 ACR70, one ACR50, one improved but did not satisfy ACR response criteria). No serious complications occurred during ASCT or up to 30 months' followup. There was prolonged reduction in CD4+ T cells. ASCT is safe and has short term efficacy. T cell purging does not prevent relapse. Five patients responded to CSA when their disease had previously been refractory, suggesting an immunomodulatory effect. No serious infectious complications occurred despite prolonged reduction in CD3+CD4+ lymphocytes.
9697140 [Radiologic results of the ARO multicenter study]. 1998 Jun We present the radiological results of 2286 total hip replacements (THR) from the multicenter study. Concerning the acetabular component the analysis showed that socket migration and radiolucent lines were much more dependent on the specific design of the socket than on the primary diagnosis. A similar results was found for the femoral stems: rheumatoid arthritis did not cause a higher percentage of stem subsidence, radiolucent lines or bone remodeling. Within a mid-term follow-up period the reduced bone quality in rheumatoid arthritis is not associated to premature failure of a cemented or cementless prosthesis. THR failure seems to be more dependent on specific construction features of the individual socket and stem.
10614169 [Expression of endothelial nitric oxide synthase and inducible nitric oxide synthase in sy 1999 Oct OBJECTIVES: To examine the localization and distribution of endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS), which participate in nitric oxide (NO) production, in synovium of rheumatoid arthritis (RA). MATERIALS AND METHODS: Immunohistochemical analysis for eNOS and iNOS in synovial tissues obtained from 10 patients with RA who were underwent total knee replacement. Synovial tissues of osteoarthritis (OA) were used as control. The percentage of cells that were positive for eNOS and iNOS was estimated in five hundred endothelial cells, synovial lining cells and interstitial cells, respectively. And mRNA expression of NOS was confirmed by in situ hybridization. In addition, to test NO production, nitration of tyrosines was assessed by immunohistochemistry. RESULTS: Not only endothelial cells but also synovial lining cells and interstitial cells exhibited immune-reactive both eNOS and iNOS. Cells which were seemed immune-reactive eNOS and iNOS expressed nitrotyrosin. By in situ hybridization, we detected mRNA expression for eNOS and iNOS. CONCLUSIONS: Endothelial cells, synovial lining cells and interstitial cells expressed both eNOS and iNOS with high frequency in RA synovium compared with OA synovium. It seemed to correlate with NO production. These results suggest that expression of iNOS may be involved in the induction of arthritis and eNOS may be participated in augmentation of inflammation in RA.
9833253 Combined elevation of IgM and IgA rheumatoid factor has high diagnostic specificity for rh 1998 The diagnostic value of measuring rheumatoid factor (RF) by agglutination or isotype-specific enzyme-linked immunosorbent assay (ELISA) was compared. The study included 70 patients with rheumatoid arthritis (RA) and 205 patients with various other rheumatic conditions. Of the RA patients, 74% were RF-positive by agglutination and 90% had one or more RF isotypes elevated by ELISA compared to 14% and 22%, respectively, of the other patients. Strikingly, 70% of the RF-positive RA patients had an elevation of two or more RF isotypes compared to only 16% of the other RF-positive patients (P < 0.0001). Furthermore, a combined elevation of IgM and IgA RF was found in 52% of the RF-positive RA patients, but only in two (4%) of the other RF-positive patients (P < 0.0001). It is concluded that a combined elevation of IgM and IgA RF is highly specific for RA and is very rarely found in rheumatic diseases other than RA. Isotype-specific RF assays are therefore diagnostically superior to agglutination tests. The detection of the RA-specific RF isotype pattern may be particularly helpful early in the course of RA even before the disease is fully differentiated.
9619892 Association of HLA-DR with susceptibility to and clinical expression of rheumatoid arthrit 1998 Apr The clinical expression of rheumatoid arthritis (RA) varies considerably among individual patients. Genetic variations in human leucocyte antigen (HLA) may influence clinical expression. We re-examined the association of HLA-DR with susceptibility to and clinical expression of RA using genomic tissue typing, since most studies were based on (less reliable) serological techniques. Seventy-eight patients with recent-onset RA, all participating in a clinical trial on therapeutic strategies, were HLA-DR typed by means of low-resolution genomic typing. Cumulative disease activity within the first 3 yr of disease was measured. Of the RA patients, 54% expressed DR4 (DR4+) vs 26% of healthy controls. Rheumatoid factor (RF)-positive patients had a higher cumulative disease activity than RF-negative patients. Patients who were either DR1+ or DR4+ had a higher cumulative disease activity than those who expressed neither DR1 nor DR4. This association was less obvious after correction for RF status. The association of DR52+ (DR3, 5, 6) and a lower cumulative disease activity could also not be demonstrated after correction for RF status. Among RF-negative patients, DR51+ (or DR2+) was associated with a higher cumulative disease activity. Other HLA-DR types (including DR1 and DR4 separately) were not associated with the severity of RA. DR4 was associated with susceptibility to RA in our patients; HLA-DR low-resolution genomic tissue typing did not yield additional information to RF status for the clinical identification of individual patients with a poor prognosis.
10952739 Racial origin and its effect on disease expression and HLA-DRB1 types in patients with rhe 2000 Aug OBJECTIVE: There are a significant number of patients with rheumatoid arthritis (RA) of North Indian or Pakistani origin (Asian) now living in the UK. RA has been poorly studied in this racial group. The aim of this study was to compare RA in this Asian group with RA in the indigenous northern European (European) population. It was hypothesized that these two racial groups would have different disease expressions and immunogenetics that could be relevant to pathogenesis, prognosis and therapy. METHODS: One hundred and seven Asian RA patients, who fulfilled the 1987 American College of Rheumatology criteria, were stringently matched for age, sex and disease duration with 107 European RA patients, and were fully assessed. RESULTS: The Asian RA patients had significantly fewer bony erosions [median Larsen score 58.5 (interquartile range 45.5-77.8) vs 68 (52-93) for European patients; P: = 0.0066, Mann-Whitney U:-test] and rarely had nodules (5.7 vs 20%, P: = 0. 0019, Fisher's exact test). The two groups had the same prevalence of rheumatoid factor positivity, number of swollen joints and level of inflammation (C-reactive protein). The Asian RA patients had a reduced prevalence of the conserved third allelic hypervariable region (3AHVR) (45 vs 82%, P: < 0.0001, Fisher's exact test), particularly DRB1*0401 (4.5 vs 55%). However, the prevalence of the conserved 3AHVR was significantly increased in the Asian RA patients compared with Asian controls. By contrast, the Asian patients had more tender joints [13.5 (7-22) vs 5.5 (2-11.8); P: < 0.0001 Mann-Whitney U:-test]. The Health Assessment Questionnaire score was also significantly worse in the Asians compared with the Europeans [median 2.0 (1.13-2.63) vs 1.25 (0.5-2.13), P: = 0.0001). CONCLUSIONS: The Asian patients had similar levels of inflammation and less damage but more pain and disability than the matched European RA patients. Of the known prognostic factors for erosions (rheumatoid factor, conserved 3AHVR, swollen joints and C-reactive protein), only the conserved 3AHVR was reduced in the Asian RA patients, and this was consistent with their less erosive disease. These data also indicate the importance of pain as well as erosive damage in determining disability in Asian patients and stress the importance of adequate pain relief, in addition to disease suppression, when treating Asian RA patients.
9213380 Oral contraceptives and rheumatoid arthritis: results from a primary care-based incident c 1997 Jun OBJECTIVE: The possibility that oral contraceptives offer a protective effect against the development of rheumatoid arthritis is still contentious. Of the 17 studies investigating this association, 11 have found a protective effect, and 6 have not. These differences are probably attributable to either selection or information biases in a subset of studies, although the exact reason is unknown. To overcome the methodological problems inherent in the design of previous studies, we have conducted a population-based case-control study. METHODS: Women who were incident cases of inflammatory polyarthritis, defined as swelling of at least two joint areas lasting at least 4 weeks, were recruited directly from primary care and compared with age-matched women from the same population. RESULTS: Cases and controls reported a similar level of "ever use" of oral contraceptives, adjusted odds ratio = 0.88 (95% confidence interval, 0.47, 1.64). The cases were, however, less likely to report using oral contraceptives at the time of onset, adjusted odds ratio = 0.22 (95% confidence interval, 0.06, 0.85). Similar results were observed for cases who satisfied the criteria for rheumatoid arthritis and cases who did not. CONCLUSION: These results indicate that only current oral contraceptive use protects against the development of inflammatory polyarthritis.
11771527 Use of isokinetic muscle strength as a measure of severity of rheumatoid arthritis: a comp 2001 The aim of this study was to study the association between isokinetic muscle strength (IMS) and other clinical indicators of disability and disease activity in patients with rheumatoid arthritis (RA). A cohort of 36 RA patients was followed over a 1-year period with five measurements of disease activity at regular intervals during this time. IMS was measured at seven angular velocities in both knees, on five separate occasions. The measurement was expressed by the level of the fitted line of the seven peak torque values--IMS30. The association between IMS30 and clinical indicators was stated. As an indicator of disability the score from the Stanford Health Assessment Questionnaire (HAQ) was used. As indicators of disease activity morning stiffness, an index of swelling and pain in the joint, erythrocyte sedimentation rate (ESR) and haemoglobin (Hb) were chosen. Larsen's X-ray score was used as an indicator of bone destruction due to longer-lasting disease activity. IMS was significantly associated with the HAQ score, but not with indicators of disease activity or radiological findings. IMS was significantly associated with changes in indicators of disease activity, but not with the changes in the HAQ score, or in the X-ray-score. IMS showed the strongest association with changes in the degree of arthritis of the knee. In conclusion, IMS was associated with the HAQ score and can therefore be used when measuring outcome in a specific group of RA patients. Changes in IMS were associated with indicators of changes in disease activity, and are therefore usable as a measure of patient outcome. Of particular importance is that IMS decreased if a patient developed active arthritis in the knee, and normalised again when the inflammation decreased.
10567974 Acromioclavicular joint subluxation is rare in rheumatoid arthritis. A radiographic 15-yea 1999 Oct AIM: To conduct a radiographic assessment of the occurrence of the acromioclavicular joint subluxation in patients with long-standing rheumatoid arthritis. METHODS: A cohort of 74 patients with seropositive rheumatoid arthritis was followed prospectively for 15 years. At the 15-year visit, plain radiographs of both shoulders (n = 148) were obtained using a standard method. Acromioclavicular joint destruction was evaluated using Larsen's method, and radiographic subluxation was measured on the radiographs using two different methods. In one of these methods (method A), the distance between the upper edge of the coracoid process and the upper surface of the clavicle was measured. The other method (method B) involved measurement of the alignment of the upper joint margins of the acromion and clavicle. RESULTS AND CONCLUSION: Two of the 148 acromioclavicular joints fulfilled criteria for subluxation with method B. Neither measurement A nor measurement B differed significantly between unaffected joints (Larsen's grade 0 or 1) and affected joints (Larsen's grade > or = 2). In addition, neither measurement was correlated with the stage of acromioclavicular joint destruction (r < 0.10 for both measurements). Measurements A and B were significantly correlated to each other (r = 0.23; 95% CI, 0.07 to 0.38). The two subluxations (one upward and one downward) occurred among the nine joints with the most severe destructive lesions (Larsen's grade 5). In conclusion, acromioclavicular joint subluxation is rare in rheumatoid arthritis, occurring only when destruction of the joint is severe. The method B used in this study may prove useful for both population studies and routine clinical work.
11246656 Abundant expression of common cytokine receptor gamma chain (CD132) in rheumatoid joints. 2001 Feb OBJECTIVE: Activated macrophages upregulate surface expression of common cytokine receptor gamma chains (gammac, CD132), triggering of which induces secretion of proinflammatory cytokines. Rheumatoid synovial tissues contain a number of macrophages that play a pathogenic role by secreting proinflammatory cytokines. We studied the expression of gammac in the rheumatoid synovial tissues. METHODS: Cryosections of synovial tissues from patients with active rheumatoid arthritis (RA) or with osteoarthritis (OA) were stained with an anti-gammac Mab. Single-cell suspensions from the rheumatoid synovial tissues were stained with the same antibody and an anti-CD14 monoclonal antibody (Mab) for 2-color flow cytometric analysis. A soluble form of gammac in synovial fluids collected from rheumatoid or OA joints was quantitated by ELISA. RESULTS: Rheumatoid synovial tissues, but not the OA tissues, expressed gammac at a high level. Flow cytometric analysis showed that gammac were expressed by virtually all CD 14 positive synovial cells in RA. Synovial fluid derived from the rheumatoid joints contained a high concentration of soluble gammac. CONCLUSION: Membrane bound and soluble forms of gammac are abundant in rheumatoid joints. They might play a complex role in the pathology of RA.
9156395 The surgical management of patients with rheumatoid cervical spine disease. 1997 May Rheumatoid arthritis is an inflammatory disease that commonly affects the cervical spine. This article reviews the incidence of spinal involvement, the clinical manifestations of spinal disease, and the types of instability patterns that may occur and their radiographic diagnosis. Appropriate guidelines for obtaining imaging studies and for surgical referral is also described. Finally, the role of surgical stabilization is discussed.
10343528 Vitamin D receptors in the rheumatoid lesion: expression by chondrocytes, macrophages, and 1999 Feb OBJECTIVES: The active form of vitamin D3, 1 alpha,25 dihydroxyvitamin D3 (1,25D3), through its interaction with vitamin D receptors (VDR), is reported to effect a variety of anabolic and catabolic events, especially in bone and cartilage tissues. As cartilage degradation and tissue remodelling are characteristic features of the rheumatoid lesion, the distribution and expression of VDR at sites of cartilage erosion was examined. METHODS: Immunolocalisation techniques using a rat monoclonal antibody to VDR and an alkaline phosphatase conjugated avidin/biotin detection system were used to examine VDR in 18 specimens of cartilage-pannus junction, 10 specimens of rheumatoid synovium or cartilage tissue, and four primary cultures of adherent rheumatoid synovial cells (RSC). For comparison, VDR expression was examined in 10 specimens of normal, healthy age matched articular cartilage. RESULTS: VDR was demonstrated in 15 of 18 cartilage-pannus junctions either at the interface (8 of 18), within the pannus tissue (12 of 18), and by chondrocytes often close to the erosive lesion (10 of 18). All the rheumatoid synovial tissue and 5 of 10 cartilage specimens showed cells with positive staining, but the extent of this was variable. Negligible VDR staining was observed for normal cartilage. Primary cultures of RSC also showed variability in both the numbers and proportions of macrophages or synovial fibroblasts stained for VDR (range 10-50%), this being more common in cultures with a high proportion of macrophages. CONCLUSIONS: VDR expression has been demonstrated by most specimens of cartilage-pannus junction; was associated with various cell types, including chondrocytes, but not exclusively with CD68+ macrophages. The focal nature of VDR expression within the rheumatoid lesion suggests a contributory role for 1 alpha,25D3 in the pathophysiological processes of rheumatoid arthritis.
9061535 Anchorage of wrist joint prostheses to bone using the osseointegration principle. 1997 Feb Five patients with rheumatoid arthritis (age 28-60 years) underwent wrist joint arthroplasty with individually designed artificial joint mechanisms, anchored to bone using the osseointegration principle. We report on the result from a 4 to 6.5 year follow-up with special emphasis on the fixation of the prosthesis to bone. There was no bone resorption or loosening of screws. Osseointegration of the titanium screws occurred in all cases and persisted throughout the observation period, although scattered lytic zones could sometimes be seen around the screws. The clinical results were satisfactory with pain relief and maintenance of a functional range of movement. The principle has prospects for fixation of a wrist joint mechanism to bone, although the presently used joint mechanism requires further refinement.
11383051 Loss of functional capacity caused by a delayed onset of DMARD therapy in rheumatoid arthr 2001 Apr The aim of this analysis was to investigate the impact of the postponement of DMARD therapy on the functional outcome of rheumatoid arthritis after 10 years of disease. 321 individuals with a disease duration of at least ten years were selected out of a cohort of more than 1800 patients. Two groups were analysed separately: patients who started DMARD therapy within the first year of their disease, and patients who received their first DMARD not earlier than five years after the onset of RA. The Keitel functional index was determined in every patient after 10 years of RA. After 10 years of disease, the swollen joint count and the ESR had decreased in both groups to a comparable degree. However, patients with early treatment performed significantly better in the Keitel test compared to the group with delayed therapy. Although patients with seropositive RA or rheumatoid nodules had a worse outcome in general, the benefit of early treatment was also significant in these subgroups.
11515604 Ankylosis of the temporomandibular joint caused by rheumatoid arthritis: a pathological st 2001 Jun Rheumatoid arthritis (RA) of the temporomandibular joint (TMJ) in a 59-year-old Japanese woman is reported, including details of clinical, histopathological and radiological findings. The patient had been diagnosed as having RA of the right knee joint 41 years previously, and suffered from arthralgia of the right TMJ. Radiological examination showed a radiopaque lesion of the mandibular head and mandibular fossa in the right TMJ and ankylosis of the right TMJ was diagnosed on the basis of the clinical and radiological findings. Condylectomy was performed. Pathological examination of material from the joint region revealed a marked increase of collagen fibers associated with slight capillary dilatation and hemorrhage. The final diagnosis was ankylosis of the right TMJ due to RA. The literature on TMJ ankylosis secondary to RA is reviewed and discussed.