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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
11477277 Alternatively spliced EDA-containing fibronectin in synovial fluid as a predictor of rheum 2001 Jul OBJECTIVES: Fibronectin containing the EDA region (EDA(+)Fn), a molecule important for rheumatoid joint destruction, was measured in relation to the progression of joint destruction in rheumatoid arthritis (RA). METHODS: Total Fn and EDA(+)Fn were measured by ELISA, and the concentrations of Fn in plasma and synovial fluid were compared prospectively for 2 yr with the progression of joint destruction in 41 knee joints of 37 patients with RA. The extent of joint destruction was assessed by the Larsen score and joint space narrowing in X-ray films taken before and 2 yr after measurement of EDA(+)Fn. RESULTS: The concentration of synovial fluid EDA(+)Fn showed a positive correlation with the progression of joint destruction in RA (r=0.78). While total Fn in synovial fluid also showed a correlation with joint destruction (r=0.54), total Fn and EDA(+)Fn in plasma showed no correlation with joint destruction. The concentration of synovial fluid EDA(+)Fn was significantly higher in patients who underwent joint replacement after the measurement of EDA(+)Fn than in those who did not receive surgery (P<0.029). CONCLUSION: Synovial fluid EDA(+)Fn can be a predictor of subsequent joint destruction in RA.
10796399 Methotrexate for rheumatoid arthritis. 2000 OBJECTIVES: To estimate the short-term efficacy and toxicity of methotrexate (MTX) for the treatment of rheumatoid arthritis (RA). SEARCH STRATEGY: We searched the Cochrane Musculoskeletal Group trials register, and Medline, up to July 1997, using the search strategy developed by the Cochrane Collaboration (Dickersin 1994). The search was complemented with bibliography searching of the reference list of the trials retrieved from the electronic search. Key experts in the area were contacted for further published and unpublished articles. SELECTION CRITERIA: Randomized controlled trials and controlled clinical trials comparing MTX against placebo in patients with RA. DATA COLLECTION AND ANALYSIS: Two reviewers determined the studies to be included based on inclusion and exclusion criteria (GW, MSA). Data were independently abstracted by two reviewers (EB, MSA), and checked by a third reviewer (BS) using a pre-developed form for the rheumatoid arthritis sub-group of the Cochrane Musculoskeletal Group. The same two reviewers, using a validated scale (Jadad 1996) assessed the methodological quality of the trials independently. Rheumatoid arthritis outcome measures were extracted from the publications. The pooled analysis was performed using standardized mean differences (SMDs) for joint counts, pain, and global and functional assessments. Weighted mean differences (WMDs) were used for erythrocyte sedimentation rate (ESR). Toxicity was evaluated with pooled odds ratios (OR) for withdrawals. A chi-square test was used to assess heterogeneity among trials. Fixed effects models were used throughout and random effects for outcomes showing heterogeneity. MAIN RESULTS: Five trials and 300 patients were included. A statistically significant benefit was observed for MTX when compared to placebo. Statistically significant differences were observed for all measures except ESR. The standardized weighted difference (effect size) between MTX and placebo for the various outcome measures varied between -0.43 and -1.5. No differences were observed in the total number of withdrawals and dropouts (OR = 0.95), although patients on MTX were three times more likely to discontinue treatment because of adverse reactions (OR=3.47) and four times less likely to withdraw due to lack of response (OR=0.22). REVIEWER'S CONCLUSIONS: Twenty-two percent of people on MTX withdrew due to adverse effects compared to seven percent of the placebo group. MTX has a substantial clinically and statistically significant benefit in the short term treatment of patients with RA.
11093442 IgA and IgG autoantibodies against alpha-fodrin as markers for Sjögren's syndrome. System 2000 Nov OBJECTIVE: To determine the prevalence of IgA and IgG autoantibodies against alpha-fodrin in patients with primary and secondary Sjögren's syndrome (SS) and controls. METHODS: An ELISA detecting IgA and IgG antibodies against alpha-fodrin was developed. We examined the prevalence of IgA and IgG antibodies against alpha-fodrin in patients with primary and secondary SS, systemic lupus erythematosus (SLE), and rheumatoid arthritis (RA) and blood donors. RESULTS: IgA antibodies against alpha-fodrin were detected in 64% of patients with primary SS (n = 85), 47% of patients with secondary SS and SLE (n = 15), and 86% of patients with secondary SS and RA (n = 7). IgA autoantibodies against alpha-fodrin were detected in only one of 160 sera obtained from blood donors and in one of 50 and 2 of 12 sera obtained from SLE and RA patients without sicca syndrome, respectively. The prevalence of IgG antibodies against alpha-fodrin in SS was lower: they were detected in 55% of sera obtained from patients with primary SS, 40% of patients with secondary SS and SLE, and in 43% of patients with secondary SS and RA. Three of 160 sera from blood donors and one of 50 and 5 of 12 sera from SLE and RA patients without sicca syndrome, respectively, contained IgG antibodies against alpha-fodrin. CONCLUSION: IgA rather than IgG antibodies against alpha-fodrin are specific for and frequently observed in primary and secondary SS and are useful markers for this autoimmune disorder.
9409647 HLA-dependent peripheral T cell receptor (TCR) repertoire formation and its modification b 1997 Dec Our previous studies have disclosed that the peripheral T cell receptor beta (TCRB) gene repertoires of RA monozygotic twins were similar. This suggested that the TCRBV repertoire is controlled primarily by genetic factors. Here, we examine how the combination of HLA and presence of RA influence the peripheral TCRB repertoire. Peripheral blood mononuclear cells from six pairs of healthy monozygotic twins, six pairs of monozygotic twins discordant for RA, and nine siblings of a large family, including three RA patients, were examined for their TCRB gene repertoires. Among healthy twins and siblings, the BV repertoires between HLA-identical pairs were significantly more similar than those of HLA-non-identical pairs. When RA-affected members were included, the repertoires of the HLA-identical pairs discordant for RA were dissimilar compared with those of healthy pairs. TCRBV-BJ combination repertoire analysis of CD4 and CD8 T cell subsets from the twins showed that the dissimilarity was primarily confined to CD8 T cells in the healthy identical twins, whereas it was seen in both CD4 and CD8 T cell subsets in the RA-discordant twins. These results suggest (i) the presence of RA modifies the genetically controlled TCR repertoire of peripheral T cells, and (ii) the RA-associated alterations appear to occur more frequently in CD4 T cells than in CD8 T cells.
10905517 Mineral dust exposure and systemic diseases. 2000 Based on clinical and immunological studies, we have proposed the hypothesis that occupational dust exposure might cause not only pneumoconiosis but also autoimmune diseases and malignancies of various organs such as neoplasms of lymphatic and hematopoietic tissues and gastric cancer. Evidence from cohort studies of pneumoconiotic patients in Japan, copper miners, and stone masons support our hypothesis. The carcinogenicity and cytotoxic effect of inhaled dust on immune cells are considered to contribute to the development of these diseases.
9315122 L-selectin expression on the surface of peripheral blood leucocytes from rheumatoid arthri 1997 Sep Recruitment of mononuclear cells from the circulation to sites of inflammation relies on migration across vessel endothelium. T and B cells, macrophages and neutrophils infiltrate synovial tissue of rheumatoid arthritis (RA) patients. The authors have analysed the numbers of circulating CD3+, CD19+ lymphocytes, monocytes, and granulocytes expressing adhesion molecules (L-selectin, CD44 and CD11a), together with levels of expression in RA patients compared to healthy individuals. Numbers of leucocytes expressing the adhesion molecules detected were similar in RA and control groups. Lower levels of expression of L-selectin on all cells were found in RA patients compared to controls. Expression of L-selectin on T and B cells was found to correlate with disease activity in RA. The authors have observed a characteristic pattern of adhesion molecule expression in RA patients, particularly when analysing the relationships between cells. The close regulation of these molecules between RA patients and healthy individuals is discussed.
11124282 An appraisal of magnetic resonance imaging of the wrist in rheumatoid arthritis. 2000 Dec OBJECTIVES: To evaluate the role of magnetic resonance imaging (MRI) in the diagnosis, staging, and follow-up of the rheumatoid wrist. METHODS: A Medline search was performed to identify all publications from the years 1985 to 1999 concerning MRI of the wrist in patients with rheumatoid arthritis (RA). Additional papers were retrieved by scanning the references to the Medline-listed articles. Details of the MRI technique, as well as clinical data, were analyzed and compared. RESULTS: A total of 55 papers were identified. There were considerable variations in imaging sequence, section type, and slice thickness. Erosions and synovitis were the conditions that mostly profited from the adoption of MRI. Although the visualization of erosions was better detailed with MRI than with conventional radiography, erosions were only rarely related to clinical and laboratory parameters. Another advantage was that synovitis imaging, which can be enhanced by contrast agents, was amenable to quantitation. The extent of the synovial surface and the rate of contrast enhancement in a series of consecutive, rapidly acquired images were the most common measures. CONCLUSIONS: MRI of the rheumatoid wrist is a useful technique to ascertain the criteria for diagnosis and progression of RA, and to monitor the effects of treatment. Implementation of a standardized protocol could further increase its value.
9041946 HLA markers and prediction of clinical course and outcome in rheumatoid arthritis. 1997 Feb OBJECTIVE: To evaluate HLA markers as early prognostic factors for disease severity in rheumatoid arthritis (RA). METHODS: HLA genotyping was carried out in a retrospective analysis of 66 RA patients and in a prospective study of 55 RA patients and 87 healthy controls using polymerase chain reaction-based methods for HLA-DRB1 specificities, DR4 alleles, and their linked DQB1 alleles, as well as HLA-B27. The clinical course of RA was assessed by clinical and radiologic scores. The impact of HLA markers was evaluated by epidemiologic means in addition to modeling using multiple logistic regression analysis. RESULTS: Shared epitope-positive (HVR3+) DR4 alleles and the HVR3 amino acid cassette QKRAA were associated with RA in both longstanding (relative risk [RR] 3.34 and 3.19) and recent-onset (RR 2.1 and 2.37) RA. In longstanding RA, radiologic evidence of severe joint destruction (Larsen score > 1.62) was seen more often in HVR3 shared epitope-positive patients than in epitope-negative patients (odds ratio [OR] = 25.67, chi 2 = 13.59, P = 0.0003). Moreover, rank sum analysis of Larsen indices indicated significantly higher ranking for the presence of the RA-associated HVR3 cassettes (QKRAA, QRRAA) when expressed on a DR4 allele (P < 0.0001). In the prospective study, DR4-positive patients had a significantly increased risk (OR = 13.75, P = 0.00083) of developing bony erosions. In addition, HVR3 epitope-positive DR4-positive individuals had significantly higher Larsen indices than did epitope-negative patients (P = 0.0083). In particular, the presence of the HVR3 epitope on DR4 resulted in an increased a posteriori likelihood (0.91) of developing early erosive disease compared with an a priori risk of 0.62. Conversely, the likelihood decreased to a minimum of 0.35 when the HVR3 epitope was absent. CONCLUSION: While the contribution of HLA typing to establishing the diagnosis of RA is limited, HLA-DR genotyping and DR4 subtype determination provide valuable markers for the prognosis of joint destruction in RA.
9448592 The relationship between psychological distress and traditional clinical variables: a 2 ye 1997 Dec In this longitudinal study (12 and 24 months follow-up) of 216 patients with early rheumatoid arthritis (RA) (< or = 4 yr duration), we assessed the strength and stability of the relationship between psychological distress and traditional clinical variables examined the ability of these clinical variables to predict changes in mental distress, and explored the directionality between mental distress and the other clinical variables. Study variables were symptoms of anxiety and depression measured by the Arthritis Impact Measurement Scales, tender joint counts, erythrocyte sedimentation rate (ESR), and self-reported pain and disability. Psychological distress showed high levels of stability over time. Pain and disability were the two variables most strongly and consistently related to mental distress. High levels of disability predicted an increase in depression during the next year; otherwise, changes in psychological distress were not predicted by disease-related variables. Attempts at causal modelling of the temporal relationship between mental distress, pain and disability failed to yield consistent results.
11074480 Treatment with cytotoxic immunosuppression agents increases urinary excretion of JCV in pa 2000 Dec Human JC virus is ubiquitous in human populations and is reactivated frequently in immunosuppressed patients. Fifty-one patients with autoimmune disease receiving immunomodulating therapy were evaluated to study the possible relationship between immunosuppression and JCV viruria. Patients were divided into cytotoxic and noncytotoxic treatment groups based on their prescription. The incidence of JCV viruria in the cytotoxic treatment group was significantly higher than that in the noncytotoxic group (67% vs. 28%; P < 0.05). Most patients with JCV viruria were receiving corticosteroid (P = 0.03 for any dose and P < 0.001 for higher-dose treatments) and cytotoxic agents (P = 0.02). Age, disease duration, and medication duration appeared not to be the precipitating factors of JCV viruria in this study. The results of clinical evaluation indicate that cytotoxic immunosuppression may play an important role in JC virus reactivation.
11296451 [A questionnaire-based survey on the Internet concerning optimal timing for knee surgery i 2001 Feb To investigate the differences between orthopedists and internists in indications for surgical management in patients with rheumatoid arthritis (RA), a questionnaire-based survey was performed on the Internet with the presentation of a case of progressive RA along with serial X-ray films of the knee. Ninety-three doctors (43 orthopedists and 50 internists, average age: 49.2 years) answered the questionnaire. Most of the doctors who viewed the X-ray film showing Larsen's grade IV chose that as the optimal time for total knee arthroplasty. No difference was noted in their choice between orthopedists and internists. Opinions varied widely, however, among younger doctors, but there was agreement among older doctors, suggesting the effect of the study and experience. On the other hand, some doctors recommended arthroscopic synovectomy for knees in the earlier stages of RA, but others did not recommend the arthroscopic surgery itself. Although this new methodology might include possible biases, we believe it should be considered in the research of rheumatology.
11396094 The role of the DR4 shared epitope in selection and commitment of autoreactive T cells in 2001 May The mechanistic basis for HLA associations with RA is still unknown in spite of 20 years of disease association studies and a detailed characterization of HLA class II alleles associated with disease. Analysis of the structural interactions between DR4 susceptibility molecules and T cells specific for the peptide-MHC complex suggests a mechanism for directed T-cell selection and amplification in which RA-associated genetic polymorphisms bias intermolecular recognition. New immunologic models for illustrating the importance of regulated thresholds for T-cell activation based on avidity between the TCR, MHC, and peptide offer insight into a potential mechanism in which the disease-associated HLA molecules create an autoimmune-prone individual by virtue of a biased TCR selection and T-cell amplification process. New tools such as the use of HLA-DR4 tetramers provide the ability to identify and monitor the presence of such autoreactive T cells in the periphery of individuals and patients and should assist in further testing of the multistep model for RA pathways presented in this article.
11434466 Pulmonary function tests, aerobic capacity, respiratory muscle strength and endurance of p 2001 Patients with rheumatoid arthritis (RA) show lower cardiorespiratory fitness than normal subjects. This study was planned to investigate the pulmonary function tests (PFT), respiratory muscle strength and endurance, and aerobic capacity of patients with RA, as well as the relationship of these parameters to clinical and functional status. Twenty-five RA patients aged 25-71 (48.52 +/- 14.09) and 21 control subjects aged 25-66 (45.67 +/- 13.27) participated in the study. PFT, maximum volunteer ventilation, maximum inspiratory and maximum expiratory pressures and cardiorespiratory exercise tests were carried out in all subjects to evaluate the respiratory involvement, inspiratory and expiratory muscle strength and endurance, and aerobic capacity. Patients' duration of disease, smoking and alcohol habits, duration of morning stiffness, visual analogue scale scores, ARA functional classifications and Ritchie articular indexes were recorded. All the patients and control subjects were non-exercising individuals. As a result, we found that RA patients have normal PFT but reduced respiratory muscle strength and endurance, and also reduced aerobic capacity compared to controls. According to this result, respiratory and aerobic exercises may be recommended to improve respiratory muscle strength and endurance and aerobic capacity in these patients.
10921143 A double blind observation for therapeutic effects of the tong luo kai bi tablets on rheum 1999 Sep The therapeutic effects of the Tong Luo Kai Bi Tablets [symbol: see text] in 120 patients with rheumatoid arthritis were observed in this clinical trial by the randomized double blind method. Both the observed group and the control group each had 60 patients. In the observed group treated with the Tong Luo Kai Bi Tablets, 1 case (1.7%) was cured clinically, 27 cases (45.0%) improved markedly, 26 cases (43.3%) improved, with a total effective rate of 90.0%. In the control group treated with Rheumatic Semen Strychni Tablets [symbol: see text], no case was cured, 16 cases (26.7%) improved markedly, 33 cases (55.0%) improved, with a total effective rate of 81.7%. Statistical data showed the Tong Luo Kai Bi Tablets had much better therapeutic effectiveness clinically than the Rheumatic Semen Strychni Tablets (P < 0.05).
10862285 Neutrophil functions in rheumatoid arthritis. 1999 Jul Neutrophils play an important role in the pathogenesis of rheumatoid arthritis by accumulation and liberation of active proteolytic enzymes. Despite the active participation of the neutrophils, the patients afflicted with rheumatoid arthritis are prone to multiple infections. We studied neutrophil functions in 20 rheumatoid arthritis patients in active disease and equal number in remission and 20 healthy normal controls. No change in neutrophil function was seen in patients in remission. Phagocytic capacity of the neutrophils in active disease was found to be significantly reduced (p < 0.05). This inversly correlated with the rheumatoid factor (r = -0.128, p = 1). Random migration and chemotaxis was statistically reduced when compared with either healthy controls (p < 0.01) or when compared with patients in remission (p < 0.01). The chemotaxis inhibition was further enhanced by autologus serum (p < 0.05). The serum from patients with active disease also reduced chemotaxis of neutrophils from normal individuals (p < 0.01), indicating reduced cellular response as well as inhibitors in serum. The positive correlation (r = 0.466, p < 0.01) with rheumatoid factor, suggests the inhibitory activity may be due to the circulating rheumatoid factor in the active disease. The postulate that prior saturation of neutrophil receptors with immune complexes lower phagocytosis as well as chemotaxis is sustained. Destruction of chemotaxis receptors by release of various strong oxidative enzymes by neutrophils may also be a factor. Normal leucocytes are seen to take up immunoglobulins from diseases serum but not from normal serum. This uptake of diseased serum may be responsible for reducing the chemotactic and phagocytic function of neutrophils and hence increased incidence of infection in these patients.
9110134 Rheumatic manifestations of neurologic and psychiatric diseases. 1997 Jan Rheumatic diseases have not proved to be more prevalent among neurologic or psychiatric patients than in the general population, except for osteoarthritis in some chronic disabling neurologic conditions (poliomyelitis, spinal cord injury). Some neurologic entities with relevant musculoskeletal manifestations are described here. The lower prevalence of rheumatoid arthritis in schizophrenia patients is mentioned, and a brief description is presented of somatoform disorders that may confound diagnosis with rheumatic diseases. Factitious disorders and malingering are frequently presented with rheumatic complaints such as low back pain and may have an important impact on the costs associated with the disease. Finally, some of the immune system abnormalities described in major depression and schizophrenia are mentioned with a clear reference to the growing field of psychoneuroimmunology. This paper will not address the issue of neurologic or psychiatric manifestations of rheumatic diseases.
10686281 The effect of reaction temperature for nephelometric assays for rheumatoid factor. 2000 Feb 25 Even using the same assay parameter, reagent and calibrator (N-latex RF kit II), the results of the assay for serum rheumatoid factors (RFs) with the Behring Nephelometer Analyzer (BNA) were higher than those with the Behring Nephelometer II Analyzer (BNII) ([BNII]=0.76 [BNA]-5.7 kIU/l, r=0.997, Sy/x=60.73, n=99). The mean bias (BNA minus BNII)+/-S.D. was 52.7+/-85.5 using the Bland and Altman plot method, and the bias was not constant. The only difference in the assay condition with the two methods was the reaction temperature with the BNA being performed at room temperature (25+/-1 degrees C) and the BNII being performed at 37 degrees C. The ratio of the results with the BNII to the BNA (BNII/BNA) ranged from 0.23 to 1.18. A significant difference was observed in the BNII/BNA ratio in patients with high levels of C-reactive protein (CRP) over 2.0 mg/l (mean BNII/BNA ratio; 0.78) in comparison to patients with normal CRP levels under 2.0 mg/l (mean BNII/BNA ratio; 0.65) (P<0.01). The RF concentrations with the BNA were reduced by addition of urea, which has been used as a mild protein-denaturing agent, and there was a significant correlation between the values calculated as (1-value treated with urea/original value without urea)x100 and the BNII/BNA ratio (r=0.652, P<0.01). These data suggested that the bias between the RF values obtained by the BNA and BNII might be caused by the variation in the reactivity of autoantibodies, which might be decreased in some inflammatory diseases.
11800080 Comparison of lymphocyte depletion and clinical effectiveness on filtration leukocytaphere 2001 Dec We evaluated the relationship between the clinical benefit of filtration leukocytapheresis (LCP) and the number of removed leukocytes in patients with rheumatoid arthritis (RA). LCP was performed in 31 drug-resistant RA patients. LCP was carried out 3 times with 1 week separating each session. Assessment of RA before and after LCP showed a substantial and rapid improvement in tender joint counts, swollen joint counts, and patients' and physicians' assessments. Careful analysis indicated that 19 of 31 patients with RA showed > or = 20% improvement following LCP therapy. The number of leukocytes in the peripheral blood significantly decreased during each session of LCP. However, there was no significant decrease in the number of circulating blood cells during the study period. No adverse reactions or complications were noted. There was no significant difference in any indices of clinical activity and the removal rates of leukocytes between responders and nonresponders. The total numbers of removed lymphocytes in responders were significantly higher than those in nonresponders (responders 64.1 x 10(8) versus nonresponders 50.7 x10(8), p < 0.05). The relationship between clinical effectiveness and the number of removed granulocytes and monocytes was not statistically significant. Our results suggest that filtration LCP to remove leukocytes from the peripheral blood, especially lymphocytes, exerts an immunomodulatory effect in patients with RA.
9852254 Cytosolic Ca2+ signalling in inflammatory neutrophils: implications for rheumatoid arthrit 1998 Feb Recognition of the ways in which neutrophil behaviour is regulated may be crucial for a full understanding of their role in inflammation and in rheumatoid arthritis. Although it is well established that changes in cytosolic free Ca2+ play a central role in triggering neutrophil responses, only recently has evidence accumulated which points strongly to the existence of two distinct Ca2+ pathways in neutrophils. One pathway is mediated by conventional agonists, such as formylated peptides, IL-8, C5a and PAF, and the other by cross-linking and immobilisation of surface receptors, such as integrins, and the Fc receptors, CD32 and CD16. In this review, we give evidence for these two signalling pathways in neutrophils, highlighting the roles of two Ca2+ storage and release organelles, one centrally located and stationary, and the other peripheral and mobile. We point out the significance of these two routes of Ca2+ signalling for the correct sequence of neutrophil responses, and suggest that aberration of this sequence could result in pathogenic neutrophil activation.
11678299 The usefulness of serum transferrin receptor and ferritin for assessing anemia in rheumato 2001 Sep OBJECTIVES: This study was aimed at investigating the usefulness of serum transferrin receptor (sTfR) and ferritin in anemic patients with rheumatoid arthritis (RA) compared with bone marrow storage iron and other tests for anemia. METHODS: Fifty-five anemic RA patients underwent anemia study. Bone marrow iron stain was performed in 18 patients. sTfR and serum ferritin levels were compared with bone marrow iron stores. RESULTS: (1) Mean sTfR concentration was 2.63+/-1.91 mg/L, (2) sTfR correlated with most indicators of anemia, (3) sTfR showed no correlation with CRP and ESR, whereas ferritin did, and (4) sTfR was higher in the "iron depleted" subgroup than in the "iron nondepleted" subgroup in bone marrow study. CONCLUSION: The measurement of sTfR and ferritin is useful in finding the cause of anemia in RA and is a possible substitute for invasive bone marrow iron study.