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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
9001168 Insulin-dependent diabetes mellitus associated with autoimmune thyroiditis and rheumatoid 1997 Jan A case associated with insulin-dependent diabetes mellitus (IDDM), rheumatoid arthritis (RA), and autoimmune thyroid disease (AITD) was reported. A high titer of anti-glutamic acid decarboxylase antibody (GAD) and a positive islet cell antigen were observed. The patient's human leukocyte antibody (HLA) haplotype was a homozygote of DQA1*0301, DQB1*0401, and DRB1*0405. Because this haplotype was in linkage disequilibrium with DPB1*0501, an allele associated with AITD in Japanese patients, the patient was homozygous for alleles susceptible to IDDM, RA, and AITD. A specific HLA haplotype susceptible to several autoimmune disease may result in the development of IDDM, RA, and AITD.
10373760 [Analysis of gene expression patterns in rheumatoid synovial fibroblasts using RAP-PCR for 1999 Apr 15 OBJECTIVE: Destruction of articular cartilage and bone by invading synovial fibroblasts is a typical histopathologic feature in rheumatoid arthritis (RA). However, little is known about specific up- or downregulation of genes leading to this aggressive phenotype. Thus, our aim was to identify genes, which are differentially expressed in RA synovial fibroblasts as compared to synovial fibroblasts derived from patients with osteoarthritis (OA) using RAP-PCR for differential display. METHODS: After extraction of total RNA, the first step of RAP-PCR was performed using various different arbitrary 10-12-base primers for first-strand cDNA synthesis. Second-strand synthesis was achieved by cycling at low stringency conditions for 35 cycles using different arbitrary 10-base primers, followed by electrophoretic separation and sequence analysis of the amplified fingerprint products. RESULTS: On average, approximately 70 different RNAs were obtained per primer, of which most were expressed both by RA and OA synovial fibroblasts. Using 26 different primer combinations, in total 12 cDNAs were differentially expressed between RA and OA synovial fibroblasts. In the RA group strong amplification of distinct PCR products suitable for sequencing could be observed. Sequence analysis identified these PCR products as highly homologous to various genes involved in regulation of cell cycle and metabolism. CONCLUSION: The data indicate that RAP-PCR is a suitable method to identify differentially expressed genes in rheumatoid synovial fibroblasts potentially involved in the specific pathophysiology of RA.
11032965 Role of cyclooxygenases in angiogenesis. 2000 Nov Angiogenesis is the process by which new blood vessels are formed. This process supports normal physiology as well as contributes to progression of disease. Progressive rheumatoid arthritis and growth of tumors are two pathologies to which angiogenesis contributes. In arthritis, we know that prostaglandins (PGs) and the enzyme cyclooxygenase-2, which catalyses prostaglandin production, are inflammatory mediators. These mediators are involved in rheumatoid arthritis and cancer-induced angiogenic processes. We discuss, herein, recent findings on the expression of cyclooxygenases in both rheumatoid arthritis and human cancer, and the links between COX-2, PGs, and angiogenesis. We also propose a model for the possible mechanistic interaction of the various cell types involved in angiogenesis.
9352043 Patient's memory or repeated pain and function scores as index for major clinical change c 1997 Change of the clinical condition is the aim of replacement of the knee. This has at least four components: a clinical phenomenon, an event for the phenomenon, size of the event and time for the event. This study dealt with major change of pain and function at the time of remission. The agreement between the patients's opinion of change and a clinical change score was poor. That a special index of changes is needed is shown in this study.
11699401 Acute myeloid leukemia in the setting of low dose weekly methotrexate therapy for rheumato 2001 Jul Methotrexate is in widespread use as second-line therapy for rheumatoid arthritis. Treatment with methotrexate in this and other settings has not been associated with the development of therapy-related leukemias. Four patients with rheumatoid arthritis are reported who developed acute myeloid leukemia (AML) while receiving low dose weekly methotrexate therapy in the absence of previous or concomitant treatment with known leukemogenic agents. AML in these four patients was of different morphologic subtypes and was associated with heterogeneous cytogenetic abnormalities, cell surface marker expression and multidrug resistance protein expression. None of the recognized features of therapy-related leukemia were present in these four nor in five previously-reported patients. It is likely that the occurrence of AML in patients with rheumatoid arthritis in the setting of methotrexate therapy represents the coincidence of these two diseases, and does not reflect a causal relationship.
11109621 [Spondylarthropathies and rheumatoid arthritis in some Finno-Ugrian populations in Russia] 2000 AIM: Determination of the prevalence of spondylarthropathies (SAP) and rheumatoid arthritis (RA) among Finno-Ugrian population of Russia. MATERIALS AND METHODS: A one stage expedition trial was made of representative samples of Mordovian and Mari populations including 1312 citizens aged over 14 years. RESULTS: Incidence rate of SAP among Mordovian and Mari examinees was 0.7 and 0.2%, respectively, ankylosing spondylitis being most frequent finding. RA occurred in 2.5 and 0.6%, respectively. All the RA cases were females without family history of this disease. CONCLUSION: SAP and RA prevalence among Mordovian and Mari populations was high but their course is more favorable than among other population of Russia.
11072594 Histology of the synovial tissue: value of semiquantitative analysis for the prediction of 2000 Sep OBJECTIVE: Routine histologic techniques are still the main procedure in the study of the synovial biopsy. The relationship between the typical histological changes of rheumatoid synovium and clinical manifestations has not been studied in detail. METHODS: With the aim of determining whether a simple semiquantitative method of evaluating the changes in closed synovial biopsies was of clinical value in assessing both the diagnosis and prognosis of rheumatoid arthritis (RA) patients, we evaluated retrospectively 72 synovial biopsy specimens (26 RA patients, 30 patients with other inflammatory diseases and 16 osteoarthritis patients). Scores (0-10) were assigned to each biopsy specimen for each of 6 histologic features: synoviocyte hyperplasia; fibrosis in the subsynovial layer; proliferating blood vessels; perivascular infiltrates of lymphocytes; focal aggregates of lymphocytes; and diffuse infiltrates of lymphocytes. Scores were compared between the 3 groups and also between the RA subgroups with early and late disease; positive and negative rheumatoid factor; with and without joint erosions; and with and without systemic disease. RESULTS: Significant differences in the mean global score (mean of the 6 scores) were found both between RA and osteoarthritis and between other inflammatory diseases and osteoarthritis (p < 0.01). The mean global score for RA was higher than the mean global score obtained for the other inflammatory diseases, but the difference was not significant. We found a significantly higher mean global score in the RA patients with erosions in comparison to the RA patients without erosions, this difference being particularly evident for the lymphocyte perivascular infiltrate (p < 0.05). There were no significant differences between the other RA subgroups. CONCLUSION: In this study we have identified differences, using routine histologic techniques, between the rheumatoid synovial membrane of patients with and without erosions. Based on our present observations we suggest that the intensity of inflammatory histological features and, in particular, a high percentage of vessels with perivascular lymphocyte infiltrate might be of prognostic value in RA.
9788397 Vasculitis-induced colonic strictures: report of two cases. 1998 Oct PURPOSE: The clinical presentations of gastrointestinal involvement from systemic vasculitis are diverse. Colonic involvement from systemic vasculitis is unusual. We report the first case of a symptomatic colonic stricture associated with rheumatoid vasculitis and another associated with systemic lupus erythematosus. METHODS: The clinical, radiologic, and histologic features of two cases of symptomatic colonic strictures secondary to colonic involvement with vasculitis are described. The literature covering gastrointestinal involvement from vasculitis in these conditions is reviewed. RESULTS: Surgical resection of the colonic strictures was required in both patients and had a satisfactory outcome. CONCLUSIONS: These cases provide further evidence of the protean clinical presentations of intestinal involvement in systemic vasculitis. Although immunosuppression has been shown to be of value in the treatment of vasculitis affecting the gastrointestinal tract, surgical resection is required for established strictures.
10986302 Meta-analysis of treatment termination rates among rheumatoid arthritis patients receiving 2000 Sep OBJECTIVE: To summarize the evidence on treatment withdrawal rates reported in observational studies and randomized controlled trials (RCTs) of methotrexate (MTX), parenteral gold (GST), sulphasalazine (SSZ) and hydroxychloroquine (HCQ) among patients with rheumatoid arthritis (RA). METHODS: Two independent Medline searches were used to retrieve relevant studies published between 1966 and 1997. Those which disclosed information on the number of patients withdrawing from the drug were retained. Cumulative probabilities of survival on treatment were then computed using actuarial survival estimates, and differences were tested using log-rank, Wilcoxon and Cox proportional hazards tests. RESULTS: A total of 159 studies provided withdrawal information, and the numbers of patients who withdrew, in general or because of inefficacy or toxicity, could be abstracted from 110 studies contributing 142 treatment arms (MTX, 48; GST, 56; SSZ, 22; HCQ, 16). Data for HCQ were available only up to 24 months, but combined percentages of patients estimated to have continued MTX, GST or SSZ, respectively, for 60 months were 36, 23 and 22% when all failures were considered, 75, 73 and 53% when withdrawals due to lack of efficacy alone were considered, and 65, 36 and 48% when only withdrawals due to toxicity were taken into account. The Cox proportional hazards test performed on all withdrawals, after adjusting for year of publication and type of study, revealed that patients remained on MTX significantly longer than they did on the other three agents; however, the patients stayed significantly longer on GST than MTX when withdrawals for inefficacy were analysed separately. No significant differences in withdrawal rates were noted between observational studies and RCTs. CONCLUSION: Patients with RA stay significantly longer on MTX than on other disease-modifying anti-rheumatic drugs. Higher withdrawal rates among those given GST are mainly due to high toxicity, whereas the majority of withdrawals from SSZ and HCQ result from lack of efficacy. Withdrawal rates in observational studies are similar to those reported in RCTs.
11740429 [Parenteral disodium-clodronate in patients with rheumatoid arthritis. A two-month open cl 2001 Dec BACKGROUND: The aim of the study was to evaluate the effect on articular pain of 100 mg of disodium-clodronate administered daily by intramuscular injection in patients affected by rheumatoid arthritis. METHODS: We studied 24 patients with established rheumatoid arthritis, in the II and III stage according to Steinbrocker. Visual analogue pain scale, physician global assessment activity and patient global assessment activity were recorded at baseline, after 30 days and after 60 days of treatment. RESULTS: VAS significant improvement after 30 days was found. The physician and patient global assessment activity were improved after 60 days of treatment. CONCLUSIONS: Disodium-clodronate given by intramuscular injection at the dose of 100 mg/die in rheumatoid patients vas effective in relieving joint pain during a two-month observation.
11005783 Motor performance of the hand in patients with rheumatoid arthritis. 2000 Oct OBJECTIVES: To examine the motor performance of the hand in a sample of patients with rheumatoid arthritis (RA). SUBJECTS: The patient group comprised 21 (two men, 19 women) patients with RA. Twenty one control subjects matched for age and sex were selected from a larger reference group, which had been drawn from the local population. METHODS: The measured motor performance aspects were simple reaction time, choice reaction time, speed of movement, finger tapping speed, and coordination (that is, speed of movement/accuracy). Results were compared for age and sex matched pairs. The measurements were made with the Human Performance Measurement/Basic Elements of Performance system, which is a multifunctional system designed to measure different motor aspects of the hands, including reaction time, movement speed, tapping speed, and coordination. RESULTS: A comparison of the results for the patient and control groups indicated that the motor functions of patients with RA were impaired in all the measured aspects (with the exception of the index finger tapping test). The difference between the groups varied between 11% and 21% for the reaction time tasks, between 12% and 18% for the speed of movement tasks, and between 15% and 17% for the coordination task. CONCLUSION: Based on the results of our research, it seems that RA decreases some motor performance functions of the hand expressed as simple reaction time, choice reaction time, speed of movement, and coordination. The changes were emphasised in movements performed with several joints.
9127090 Direct posterior-posterior triangulation of the knee joint. 1997 Apr To perform surgery in the inaccessible area of the posterior compartment of the knee joint with the conventional anterior-posterior triangulation technique, we have used a direct posteromedial-posterolateral triangulation technique. This technique has been easy and safe in performing arthroscopic surgery in the posterior compartment, including synovectomy of 350 knees and removal of loose bodies in 12 knees. Using this method in addition to conventional anterior-posterior triangulation, the whole area of the posterior compartment could be covered for performing arthroscopic surgery.
11407684 Primary association of a MICA allele with protection against rheumatoid arthritis. 2001 Jun OBJECTIVE: To determine whether major histocompatibility complex class I chain-related gene A (MICA) polymorphisms are associated with susceptibility to rheumatoid arthritis (RA) independently of the HLA-DRB1 shared epitope (SE). METHODS: Fifty-four Spanish families with an affected son or daughter and 211 consecutive RA patients were genotyped for HLA-DRB1, tumor necrosis factor a/b microsatellite alleles, and MICA transmembrane polymorphism. We performed a case-control comparison with the consecutive patients and an independent transmission disequilibrium test with the families. RESULTS: The frequency of the MICA 6.0 allele was significantly reduced, compared with controls, in the group of SE+ patients (odds ratio 0.39, P = 0.0005). Additionally, the haplotypes containing this allele were preferentially not transmitted to the affected offspring (9 transmitted of 33; P = 0.007), independent of the presence or absence of an SE either in the same haplotype or in the other haplotype in the progenitor. CONCLUSION: These data suggest that the MICA 6.0 allele is an independent marker of protection against RA in the SE+ group of RA patients.
11554047 [Rheumatic pain]. 2001 Sep RA is a chronic inflammatory arthropathy that characterized by joint destruction with invasive proliferation of synovial cells in articular cartilage. Inflammatory cytokines like TNF-alpha, IL-1 and IL-6 are overproduced and play an important role in the process. In order to relief patient's chronic pain and to prevent of joint destruction, NSAIDs, steroids and DMARDs are common. Recently, anti-cytokine therapy develop and neutralizing antibody to TNF-alpha (infliximab) and TNF-alpha receptor/IgG fusion protein(etanercept) are already used in U.S.A. and in Europe. In Japan, these medicines are now on clinical trial and will be available in a few years. Other anti-cytokine therapy like IL-1 receptor antagonist and anti-IL-6 receptor antibody is also on clinical trial.
9645608 Regulation by transforming growth factor-beta1 of class II mRNA and protein expression in 1998 May Transforming growth factor (TGF)-beta1 is an immunosuppressive cytokine that modulates the expression of class II histocompatibility antigens on human cells. Aberrant HLA class II expression on synovial lining cells of rheumatoid arthritis synovial membrane has been described, and the extent and intensity of class II expression on the cells was claimed to be linked with the severity of the disease. In this study, the effects of TGF-beta1 on HLA class II antigen expression in fibroblast-like synoviocytes (SFC) from rheumatoid synovectomy tissues were determined by flow cytometric analysis and quantitative RT-PCR. We found that pre-incubation of cells with TGF-beta1 was able to down-regulate IFN-gamma-induced DR protein expression in SFC. TGF-beta1, additionally, down-regulated IFN-gamma-stimulated class II transactivator (CIITA) and DRB mRNA expression. The constitutive expression of CIITA mRNA was completely abolished and the constitutive expression of DRB mRNA was decreased after treatment of SFC with TGF-beta1 for 24 h. Addition of the TGF-beta inhibitor decorin to SFC for 24 h before TGF-beta1/IFN-gamma treatment was able to reduce the down-regulatory effect of TGF-beta1 on DR antigen expression induced by IFN-gamma. Using competitive RT-PCR, we found that SFC constitutively expressed decorin mRNA and that treatment of cells with TGF-beta1 for 24 h reduced the constitutive expression of decorin mRNA by 65%. Our results show that TGF-beta1 is able to reduce the expression of HLA class II mRNA and protein, and suggest a tight regulation between TGF-beta1 and decorin in SFC of the rheumatoid synovium.
11210737 [Antigen-specific T cells transduced with interleukin-10 ameliorate experimentally induced 2000 Dec For the treatment of rheumatoid arthritis, efficient drug delivery methods to the inflamed joints need to be developed. Since T cells expressing an appropriate autoantigen-specific receptor can migrate to inflamed lesions, it has been reasoned that they can be employed to deliver therapeutic agents. In order to examine the ability and efficiency of such T cells as a vehicle, we employed an experimentally induced model of arthritis. Splenic T cells from DO 11.10 T cell receptor transgenic mice specific for OVA were transduced with murine IL-10. Adoptive transfer of the IL-10-transduced DO 11.10 splenocytes ameliorated OVA-induced arthritis, in spite of the presence of around 95% non-transduced cells. Using GFP as a marker for selection, the number of transferred cells needed to ameliorate the disease was able to be reduced to 10(4). Preferential accumulation of the transferred T cells was observed in the inflamed joint, and the improvement in the disease was not accompanied by impairment of the systemic immune response to the antigen, suggesting that the transferred T cells exert their antiinflammatory task locally, mainly in the joints where the antigen exists. In addition, IL-10-transduced DO 11.10 T cells ameriolated mBSA-induced arthritis when the arthritic joint was co-injected with OVA in addition to mBSA. These results suggest that T cells specific for a joint specific antigen would be useful as a therapeutic vehicle in rheumatoid arthritis for which the arthritic autoantigen is still unknown.
10773354 Identification of four novel dinucleotide repeat polymorphisms in the TNF-alpha and TNF-be 2000 May Five polymorphic regions (a to e) have been recognized within the TNF gene region. These polymorphisms appear to be of biological importance as individual alleles have been associated with higher production of TNF and/or an increased risk of rheumatoid arthritis or diabetes mellitus. We report here the detection of four new alleles designated a14 (122 bp), b8 (131 bp), b9 (132 bp), and d0 (122 bp) in patients with rheumatoid arthritis and normal controls from the Pacific Northwest. This increases to 39 the number of alleles now recognized at these loci.
9665275 Blocking cytokines with genes. 1998 Jul The pathophysiology of rheumatoid arthritis (RA) is primarily driven by proinflammatory cytokines such as interleukin-1 (IL-1) and tumor necrosis factor alpha. Several biological agents have been identified that effectively block the activity of these cellular messengers, and administration of these agents to animal models of RA and human patients has been found to have therapeutic benefit. The application of gene therapy for the treatment of RA and other articular diseases is being explored to overcome current limitations with delivery of therapeutics to joint tissues. To date, laboratory research has focused on two main areas: (1) evaluation of gene delivery approaches and (2) identification of therapeutic gene products. Considerable progress has been reported with the use of local gene delivery to synovial cells by both in vivo and ex vivo methods and by systemic administration of gene delivery vectors via the circulation. Gene products that have therapeutic efficacy in animal models of RA include: IL-1 receptor antagonist, soluble IL-1 receptor I, soluble tumor necrosis factor receptor II, viral IL-10, and transforming growth factor beta, among others. The success of these laboratory studies has led to the implementation of a Phase I clinical trial to asses the safety and feasibility of using gene therapy in the treatment of RA.
11197967 Evaluation of 99mTc-RP128 as a potential inflammation imaging agent: human dosimetry and f 2001 Jan 99mTc-RP128 is a bifunctional peptide chelate designed to target the tuftsin receptor, expressed by neutrophils, monocytes, and macrophages. Studies in animal models of both infectious and noninfectious inflammation have shown a positive correlation between accumulation of 99mTc-RP128 and quantitative measures of inflammation. A phase 1 trial was conducted with the objective of determining the safety, biodistribution, and human dosimetry of 99mTc-RP128 in eight healthy volunteers. For evaluation of the potential of 99mTc-RP128 for imaging sites of inflammation, 10 patients with active rheumatoid arthritis were studied. METHODS: Normal biodistribution was determined using the conjugate view method up to 24 h after intravenous injection of 280 MBq 99mTc-RP128. Dosimetry calculations were based on standard MIRD methodology, using the International Commission on Radiological Protection model 30 of the gastrointestinal tract and a voiding bladder model with an interval of 4.8 h. For rheumatoid arthritis patients, whole-body scans and spot views of the hands, knees, and feet were obtained at 1 and 3 h after injection of 475 MBq 99mTc-RP128. RESULTS: 99mTc-RP128 was cleared rapidly from the blood by renal excretion, and no major organs showed significant accumulation. The synovia of the major joints were visualized for all subjects. The effective dose equivalent and the effective dose were calculated to be 0.011 and 0.0094 mSv/MBq, respectively. The highest dose was to the bladder wall, which received 0.076 mGy/MBq. In all rheumatoid arthritis patients, we observed a markedly increased uptake in several affected joints. Painful and swollen joints were detected with a sensitivity of 76% and 69%, respectively. Seventy-three percent of the joints with radiographic signs of erosion were scintigraphically positive. In some patients, lines of increased activity were observed and were considered to correspond to uptake in the synovium lining tendon sheaths in the wrists and hands. CONCLUSION: This study shows that 99mTc-RP128 is safe and can successfully be used to visualize clinically affected joints in patients with long-standing rheumatoid arthritis. A proposed radioactive dose of 450-500 MBq will produce an effective dose well within the range of effective doses for commonly used radiopharmaceuticals.
9384396 Vertical translocation. Part II. Outcomes after surgical treatment of rheumatoid cervical 1997 Dec This is a prospective observational study in 116 patients with rheumatoid arthritis and vertical translocation who underwent cervical spine surgery after developing symptomatic myelopathy. These patients, whose mean age was 62 years, had suffered from rheumatoid arthritis for almost 25 years. Surgery was performed via a combination of anterior (67 transoral decompressions) and posterior approaches. Surgical morbidity was recorded in 39% of patients, with a 30-day mortality rate of 10.3%, which was largely related to poor preoperative neurological grade. Neurological improvement of at least one Ranawat class was observed in 55 patients. Univariate analysis revealed the following clinical variables to be associated with a good neurological outcome (Ranawat class): younger age and good preoperative muscle power. Significant radiological variables included the degree of vertical translocation as measured by the Redlund-Johnell method and the preoperative spinal cord area. The degree of transgression in the foramen magnum did not significantly affect neurological outcome. Neither the anterior nor the posterior atlantodens interval predicted neurological recovery. Multiple logistic regression models were constructed based on the preliminary evidence of the authors' univariate analysis and these confirmed the importance of preoperative neurological function, spinal cord area, and the degree of vertical translocation in influencing the final neurological grade.