Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
ID | PMID | Title | PublicationDate | abstract |
---|---|---|---|---|
15570234 | Arthroscopic synovectomy for the rheumatoid elbow: a short-term outcome. | 2004 Nov | We evaluated the results of arthroscopic synovectomy of 11 rheumatoid elbows in 10 patients. All patients had severe pain and swelling, resulting from chronic synovitis, that had not responded to conservative treatment. We divided the patients into two groups according to preoperative Larsen grade: group A, grade 1, 2, or 3 (n = 6); and group B, grade 4 (n = 5). The visual analog scale and the Elbow Evaluation Sheet of the Japanese Orthopaedic Association were used for preoperative and postoperative evaluation of pain and function. Arthroscopy was performed by use of the procedure of Poehling et al, without resection of the radial head. The mean follow-up period was 37 months. Visual analog scale and Japanese Orthopaedic Association scores improved significantly in both groups, with relief of pain and satisfactory functional results. We recommend this procedure for patients with a persistently painful, swollen elbow with Larsen grade 1 to 4 due to rheumatoid arthritis. | |
15551000 | Inflammatory cytokine levels in paw tissues during development of rat collagen-induced art | 2004 Sep | OBJECTIVE AND DESIGN: To characterize rat collagen-induced arthritis (CIA) on the basis of levels of inflammatory cytokines, tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta and IL-6 in paw tissues, and further investigate the effect of FK506 (tacrolimus), a potent inhibitor of T cell activation, on cytokine levels. METHODS: CIA was induced in female Lewis rats. The volume of hindpaws was measured before and after collagen immunization. TNF-alpha, IL-1beta and IL-6 levels in paw tissue extracts were determined by ELISA. Proteoglycan contents of cartilage in femoral heads was measured as an indication of cartilage destruction. To assess the effect of FK506 on inflammatory cytokine levels, rats were orally treated with 5 mg/kg of FK506 from days 14-21. RESULTS: TNF-alpha a level in paw tissues did not significantly change compared to levels found before collagen immunization, throughout development of CIA. In contrast, IL-1beta and IL-6 levels in paw tissues significantly increased between day 14 and day 28 after collagen imuninization, when the arthritis was at a developed stage. Therapeutic treatment with FK506 reduced the elevated level of IL-6, but not IL-1beta, in paw tissue. FK506 treatment was effective in suppressing paw swelling and also recovering the loss of proteoglycan contents in the cartilage. CONCLUSIONS: Levels of IL-1beta and IL-6, but not TNF-alpha , in paw tissue were upregulated in association with the development of arthritis in rat CIA. These results suggest that IL-1beta and IL-6, rather than TNF-alpha , may play important roles at local inflammatory sites in producing joint destruction in rat CIA. FK506 may improve arthritis in established stages of CIA, by reducing the elevated level of IL-6. | |
14564272 | Reoperation rate after elbow synovectomy in rheumatoid arthritis. | 2003 Sep | The purpose of this study was to evaluate the reoperation rate of elbow synovectomy in patients with rheumatoid arthritis. A total of 103 synovectomies were performed in 88 patients (61 women) with rheumatoid factor-positive rheumatoid arthritis with a mean follow-up of 5.2 years (range, 1-8 years). The survival rate after elbow synovectomy (free from reoperation) was 77% (95% confidence interval, 66%-85%) at 5 years. Eight resynovectomies and fourteen total elbow replacements were performed during the follow-up. No significant improvement in range of motion was detected after synovectomy, but pain relief and patient satisfaction were favorable. Elbows were classified preoperatively (before primary synovectomy) with the Larsen system. All resynovectomies were performed for elbows of grade 0-2 destruction. A significant difference was found between early (Larsen grade 0-2) and late (Larsen grade 3) synovectomies in relation to elbow replacement (P =.002) during the follow-up. Late synovectomy yielded more temporary pain relief with a high rate of elbow arthroplasties. | |
15361374 | Decrease of anti-cyclic citrullinated peptide antibodies and rheumatoid factor following a | 2004 Oct | OBJECTIVE: To investigate the effect of infliximab treatment on anti-cyclic citrullinated peptide antibodies (anti-CCP) and rheumatoid factor (RF) in patients with rheumatoid arthritis. METHODS: 43 patients with rheumatoid arthritis not responding to disease modifying anti-rheumatic drugs (DMARD) received intravenous infliximab at a dose of 3 mg/kg at baseline and after two and six weeks, and subsequently bimonthly, in combination with methotrexate. Serum samples were collected at baseline and at week 24. A commercial enzyme linked immunosorbent assay was used to test for anti-CCP antibodies; RF were detected using a quantitative nephelometric assay. RESULTS: At baseline, 38 of the 43 patients (88%) were positive for anti-CCP antibodies, and 41 (95%) were positive for RF. The serum titre of anti-CCP and RF decreased significantly after six months of treatment (p = 0.0001 and p<0.0001, respectively). When the patients were grouped on the basis of their clinical response to infliximab, a significant decrease in serum anti-CCP antibodies and RF was observed only in patients who had clinical improvement (ACR 20 and ACR 50). CONCLUSIONS: Anti-TNFalpha treatment in rheumatoid arthritis results in a decrease in the serum titres of RF and anti-CCP antibodies in patients showing clinical improvement, suggesting that these measurements may be a useful adjunct in assessing treatment efficacy. | |
12045428 | Utility of Tc-99m human polyclonal immunoglobulin G scintigraphy for assessing the efficac | 2002 Jun | PURPOSE: The aim of this study was to determine the utility of Tc-99m human polyclonal immunoglobulin G (HIG) scintigraphy for evaluating the efficacy of yttrium-90 (Y-90) silicate therapy in rheumatoid knee synovitis. MATERIALS AND METHODS: Fifteen patients (13 women, 2 men; mean age, 53.5 +/- 8.4 years) with rheumatoid arthritis had radionuclide synovectomy using 185 MBq (5 mCi) Y-90 silicate to evaluate 24 knee joints with chronic persistent synovitis. Radiologic and clinical evaluations and Tc-99m HIG scans were performed in each patient before radionuclide synovectomy. Each patient was reassessed 3, 6, 9, and 12 months after therapy using clinical examination and Tc-99m HIG scintigraphy. RESULTS: In 14 of 24 knee joints (4 Larsen stage I, 10 Larsen stage II) that had excellent or good clinical responses to Y-90 silicate therapy, the Tc-99m HIG index values 3 months after treatment were significantly lower than the pretreatment index values (P < 0.001). In 13 of these 14 joints, these low index values and clinical results remained constant throughout the 1 year of follow-up. One patient (1 of the 14 knee joints) experienced severe pain and swelling as a result of recurrent arthritis at 9 months, and the Tc-99m HIG index value increased at 9 months and remained high 12 months after therapy. In 10 of 24 knee joints (4 Larsen stage II, 6 Larsen stage III) that had a fair or poor clinical response, Tc-99m HIG index values were statistically similar before and after radionuclide therapy. CONCLUSIONS: Quantitative Tc-99m HIG scintigraphy is a valuable method for assessing the efficacy of Y-90 silicate therapy in rheumatoid knee synovitis. | |
14672883 | TNF inhibitors in the treatment of rheumatoid arthritis in clinical practice: costs and ou | 2004 Jan | OBJECTIVES: To evaluate costs, benefits, and cost effectiveness of tumour necrosis factor inhibitor treatment over one year in routine clinical practice. MATERIALS AND METHODS: At four rheumatology units in southern Sweden treatment of 160 consecutive patients with RA was started with either etanercept or infliximab. The economic analysis was based on 116 patients with complete data who received treatment for at least one year. Details on drug treatment, functional capacity, disease activity, and laboratory values were available during the entire treatment. Information on resource use and QoL was collected at baseline and throughout the first year. The cost effectiveness analysis was based on changes in outcome and costs compared with the year before treatment. Cost per quality adjusted life year (QALY) gained was calculated for the entire sample and for patients with different levels of functional disability. RESULTS: During the first treatment year direct costs were reduced by 40%, but indirect costs did not change substantially. Patients' QoL improved on treatment-utility increased from an average of 0.28 to 0.65. Assuming that improvement occurred after three months' treatment, the cost per QALY gained is estimated as euro;43 500. If it occurs after six weeks, in parallel with clinical measures, the cost per QALY is euro;36 900. Sensitivity analysis, including all 160 patients, gave an estimated cost per QALY of euro;53 600. The cost per QALY increases for patient groups with less severe disease. CONCLUSION: For this patient group, cost effectiveness ratios are within the generally accepted threshold of euro;50 000, but need to be confirmed with larger samples. | |
15308576 | Immature dendritic cell transdifferentiation into osteoclasts: a novel pathway sustained b | 2004 Dec 15 | Dendritic cells (DCs), the mononuclear cells that initiate immune response, and osteoclasts, the multinucleated bone-resorbing cells, are derived from monocyte/macrophage precursor cells. Granulocyte-macrophage colony-stimulating factor and macrophage colony-stimulating factor (M-CSF) reciprocally regulate the differentiation of both lineages in mice. Using human monocyte-derived DCs generated in vitro, we show that immature DCs transdifferentiate into functional osteoclasts (OCs) in the presence of M-CSF and receptor activator of nuclear factor-kappaB ligand (RANKL). Transdifferentiation operates through fusion of intermediate adherent bipolar fusiform mononuclear cells expressing CD14, CD1a, and RANKL and able to induce RANKL(+) T-cell proliferation. Surprisingly, DC fusion in vitro is faster and more efficient than monocyte fusion to form multinucleated giant cells. The transdifferentiation process reported here supports the existence of a high cellular plasticity within differentiated myeloid phagocytes. Importantly, this process is greatly enhanced by rheumatoid arthritis synovial fluid and involves proinflammatory cytokines such as interleukin 1 or tumor necrosis factor alpha, as well as components of the extracellular matrix such as hyaluronic acid. Our data therefore suggest that DC-derived OCs may be directly involved in the osteolytic lesions observed in human inflammatory bone diseases such as rheumatoid arthritis or in particular forms of Langerhans cell histiocytosis, characterized by accumulation of immature skin DCs and chronic lytic bone lesions. | |
12426849 | [Functional capacity and cartilage oligomeric protein (COMP) in serum of patients with mat | 2002 Aug | OBJECTIVE: To compare late onset with adult onset rheumatoid arthritis. METHODS: Fifty-eight patients with late onset rheumatoid arthritis (LORA) were compared to 117 patients with adult onset rheumatoid arthritis (AORA) with respect to clinical and functional parameters. Furthermore, in 104 patients serum cartilage oligomeric matrix protein (COMP) was measured. Results were compared by means of ANOVA and possible influences of age, gender and clinical parameters were evaluated by Spearman rank correlation. RESULTS: Except a different distribution in gender (40% males in the LORA group) and a higher ESR, no differences could be found with respect to clinical parameters. However, a significantly higher HAQ score and significantly higher serum-COMP levels could be shown in the LORA group. HAQ scores correlated not only with disease activity parameters (C-reactive protein, disease activity score) but also with the age. Serum-COMP levels did show a correlation with the age as well, but not with disease activity. CONCLUSION: It is concluded that the higher serum-COMP levels in late onset rheumatoid arthritis could be due to concomitant osteoarthritic processes in larger joints, which are not symptomatic. The age dependence of the HAQ score is only weak, but may be the reason why patients with LORA show a worse functional capacity compared to patients with adult onset rheumatoid arthritis. | |
12211526 | High-dose immunoablative therapy with hematopoietic stem cell support in the treatment of | 2002 Aug | In the past 5 years approximately 500 patients worldwide suffering from severe autoimmune disease (AD) have received an autologous hematopoietic stem cell transplantation (HSCT) as treatment following high-dose chemotherapy. The EBMT and EULAR data base contains 370 registrations, the most frequently transplanted ADs being multiple sclerosis (MS), systemic sclerosis (SSc), rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA), systemic lupus erythematosus (SLE) and idiopathic thrombocytopenic purpura (ITP). Around 70% responded initially well, with durable remission/stabilization seen more frequently in MS and SSc than in RA and SLE, the latter having around 2/3 relapses, the majority of which respond to simple agents. Overall 8% transplant-related mortality was seen with large inter AD differences (12.5% in SSc and only one patient in RA) probably reflecting the degree of vital organ involvement at the time of transplant. This phase I/II data has led to a running phase III randomized trial in SSc called the Autologous Stem cell Transplantation International Scleroderma (ASTIS) trial, and it will soon begin in MS (ASTIMS) and RA (ASTIRA). The concept of immunological "re-setting" has evolved, and needs to be confirmed by longer follow-up and the multicentre, international phase III randomized studies. | |
15115713 | Differential effects of leflunomide and methotrexate on cytokine production in rheumatoid | 2004 Sep | BACKGROUND: T cells have a pivotal role in RA. Leflunomide inhibits pyrimidine biosynthesis, to which T cells are especially susceptible, and therefore may have a different cytokine profile than methotrexate. MATERIALS AND METHODS: Serum samples of 100 patients with RA, treated with leflunomide (n = 50) or methotrexate (n = 50), were collected at baseline, after 16 weeks and after 1 year's treatment. Serum levels of interleukin 6 (IL6), and interferon (IFN) gamma were determined by ELISA. Additionally, peripheral blood mononuclear cells (PBMC) of five healthy volunteers and three patients with RA were isolated and the effects of the active metabolite of leflunomide (A77-1726, 0-200 mmol/l) on cell proliferation and on IL6 and IFNgamma production were determined by ELISA. In peripheral blood lymphocytes (PBL) and monocytes (PBM) from two healthy volunteers the effects of A77-1726 on IL6 production were measured by ELISA and PCR. RESULTS: Mean (SEM) serum levels of IFNgamma were significantly reduced after leflunomide treatment (baseline 43 (10) pg/ml; 1 year 29 (7) (p = 0.015), but there was no change in IL6 levels (baseline 158 (41), 1 year 151 (48)). Both IFNgamma and IL6 levels were significantly reduced after methotrexate treatment. This observation was supported by in vitro experiments. The production of IFNgamma by PBL was inhibited by A77-1726, but IL6 production by PBM was not inhibited. CONCLUSION: The differential effect on IFNgamma and IL6 production supports the hypothesis that activated T cells are preferentially inhibited by leflunomide. An explanation may be either inhibition of uridine synthesis or effects on signal transduction pathways. | |
12491121 | [Diagnostics]. | 2002 | The round-table group "diagnostic" discussed the laboratory-based diagnosis of rheumatic diseases under the following three main questions: "What is necessary?"; "What is possible?" and "What has been achieved?". | |
12730503 | Rheumatoid factor is the strongest predictor of radiological progression of rheumatoid art | 2003 Aug | OBJECTIVE: To evaluate the predictive value of clinical, biological and radiological parameters for the prognosis of rheumatoid arthritis (RA) in a community-recruited cohort. METHODS: Ninety-one patients (mean age 49 yr, female/male ratio 2.9) with RA of limited duration (median 2 yr), 80% recruited from the community, were prospectively enrolled in 1996 (T1) and followed until 1999 (T2). Data collected at T1 were demographic characteristics, Ritchie articular index (RAI), extra-articular manifestations, Health Assessment Questionnaire (HAQ) score, C-reactive protein (CRP) and autoantibodies (autoAbs) [rheumatoid factors (RF), detected by latex fixation test and ELISA (IgM, IgA and IgG isotypes), anti-filaggrin, detected by immunofluorescence (anti-keratin antibodies, AKA; anti-perinuclear factor antibodies, APF) and ELISA (anti-citrullinated rat filaggrin antibodies, ACRFA), anti-Sa, anti-calpastatin recognizing the 27 C-terminal fragment (ACAST-C27) and domain I (ACAST-DI), anti-cardiolipin (ACL), antineutrophil cytoplasmic antibodies (ANCA), anti-annexin V (aANX V) and anti-Ro]. Hands were radiographed at T1 and T2, and read using the Sharp method as modified by van der Heijde. The main assessment criterion was progression of radiologically detected damage between T1 and T2. RESULTS: At T1, RA activity was mild (RAI 11/78; mean CRP 14 mg/ml), with minor functional disability (HAQ 0.8/3) and mild X-ray destruction (mean total Sharp score 9.2/280). At T1, 96% of the patients were on treatment (prednisone 72%, DMARDs 95%). The latex test detected autoAb in 46% of patients, RF-IgM was detected in 51%, RF-IgA in 36%, RF-IgG in 32%, AKA in 33%, APF in 45%, ACRFA in 45%, ACAST-C27 in 14%, ACAST-DI in 5%, anti-Sa in 22%, ACL in 3%, ANCA in 28%, aANX V in 9% and anti-Ro in 2%. At T2, the mean total Sharp score was 22.9. According to univariate analysis, T1 parameters associated with the independent variable were RAI, HAQ, CRP, latex test positivity and T1 Sharp scores. Multivariate analysis retained only latex test positivity and, to a lesser degree, joint-space narrowing score as independent predictors of radiological progression. CONCLUSION: RF is the main factor that can predict radiological progression in community cases of RA of limited duration. | |
12952023 | Treatment of rheumatoid arthritis with imatinib mesylate: clinical improvement in three re | 2003 | BACKGROUND: Imatinib mesylate is an inhibitor of a few tyrosine kinases including KIT, which is an important growth factor receptor of mast cells. AIM: To study the efficacy and safety of imatinib in the treatment of rheumatoid arthritis. METHOD: Three patients with severe rheumatoid were treated with imatinib for 12 weeks. The number of tender and swollen joints, patient-assessed disease activity and pain as assessed by a visual analogue scale, a health assessment questionnaire (HAQ) score, serum C-reactive protein (CRP) and blood erythrocyte sedimentation rate (ESR) were used as the primary outcome measures. RESULTS: All outcome measures improved. The swollen joint count decreased in all patients, and the tender joint count in two of the three patients. The patients reported less pain and disease activity, and the HAQ scores improved. Serum CRP and blood ESR improved in two patients. One patient interrupted therapy due to a rash. CONCLUSIONS: Imatinib mesylate may have considerable anti-rheumatic efficacy. The mechanism of action is not known, but one possible target for the action of imatinib is inhibition of the KIT receptor on mast cells. | |
12022347 | Rheumatoid flat foot and deformity of the first ray. | 2002 May | OBJECTIVE: To study the relationship between flat foot and forefoot deformities in rheumatoid arthritis (RA) in order to improve understanding of the progression of deformity and thus provide more appropriate treatment. METHODS: Anteroposterior and lateral weight-bearing radiographs were obtained of 308 feet of patients with RA and 202 feet of patients with neck pain (control feet). RESULTS: In women with RA, we observed with disease duration an increased frequency of flat foot that was correlated with first ray deformity (chiefly metatarsus primus adductus) and severe stages of disability. Flat foot increased very markedly after 3-4 years of disease duration. In control women, flat feet were more frequent after the age of 50 years. CONCLUSION: In RA the inflammatory and mechanical factors leading to foot deformity must receive early medical treatment to avoid progressive hindfoot deformities that lead to disability. | |
12581498 | Tumour necrosis factor-alpha, interleukin-2 soluble receptor and different inflammatory pa | 2002 Dec | BACKGROUND AND AIMS: Although the participation of cytokines in the pathogenesis of rheumatoid arthritis (RA) seems to be unequivocal, their relationship with current serum markers of this disease is not clear. The present study analyses whether there is any correlation between the levels of tumour necrosis factor-alpha (TNF-alpha), interleukin-2 soluble receptor (sIL-2R) and the concentrations of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and beta(2)-microglobulin in a group of 21 patients with RA, all rheumatoid factor positive. METHODS: The levels of TNF-alpha and sIL-2R were analysed in association with other parameters of inflammation (ESR, CRP and beta(2)-microglobulin). RESULTS: In comparison with the control group, RA patients presented high median levels of both cytokines, TNF-alpha (6.4 pg/ml) and sIL-2R (56 pmol/L), as well as of ESR (34 mm/h), CRP (0.9 mg/dl) and beta(2)-microglobulin (1.6 mg/dl) (p < 0.01). However, only ESR levels in the RA group significantly differ from the control group (p < 0.01). No correlation was found between the inflammatory parameters. CONCLUSIONS: These results suggested that TNF-alpha and slL-2R levels are up-regulated in RA patients but did not significantly differ from the control group. Due to the chronic course of this disease, other inflammatory markers must be identified in order to provide early therapeutic strategies to these patients. | |
14719202 | Autoantibodies to tissue transglutaminase in Sjögren's syndrome and related rheumatic dis | 2003 Dec | OBJECTIVE: Sjögren's syndrome (SS) has been reported in up to 15% of patients with biopsy proven celiac disease (CD). The diagnosis of CD in the setting of SS and other systemic rheumatic diseases can be difficult because they are often associated with a number of gastrointestinal symptoms and diseases. Although the diagnosis of CD is often confirmed by a small bowel biopsy, marker autoantibodies directed against the endomysium of transitional epithelium (EMA) and tissue transglutaminase (tTG) are highly correlated with biopsy-proven disease and serve as a valuable screening test. We used an IgA-anti-tissue transglutaminase antibody (anti-tTG) ELISA to assess the prevalence of anti-tTG in an unselected cohort of patients with SS and other systemic rheumatic diseases. METHODS: Sera from 50 patients with SS, 50 with systemic lupus erythematosus (SLE), 50 with rheumatoid arthritis (RA), 30 with systemic sclerosis (SSc), and 50 healthy controls were tested for autoantibodies to tTG. A comparison group of 40 sera from patients with biopsy-confirmed CD was also included. IgA anti-tTG was measured by a commercially available ELISA kit (Inova, San Diego, CA) that employs purified tTG. RESULTS: Six of the 50 (12%) IgA sufficient SS patients had anti-tTG compared to 2 (4%) normal sera, 3 (6%) SLE, 2 (7%) SSc, and 1 (2%) RA. By comparison, in the CD cohort, 33 (83%) had anti-tTG. Five of 6 SS patients with anti-tTG had symptoms, signs, or small bowel biopsy findings consistent with a diagnosis of CD. IgA anti-tTG and EMA were accompanied by other IgA autoantibodies in SS sera. CONCLUSION: Anti-tTG ELISA is a reliable method to indicate a coexisting diagnosis of CD in patients with SS. Interestingly, the frequency of false positive tTG tests in any of the systemic rheumatic diseases is not significantly greater than in controls. Further, our study shows that anti-tTG is more prevalent in SS than in other systemic rheumatic diseases. The tTG ELISA may be used as a screening test to identify patients with SS who are at risk and require further evaluation for the presence of CD. | |
12219317 | Vasculitis secondary to staphylococcal Protein A immunoadsorption (Prosorba column) treatm | 2002 Aug | OBJECTIVE: Vasculitis is a rare complication of immunoadsorption treatment with staphylococcal Protein A (Prosorba column). The prevalence, clinical characteristics, pathophysiology, treatment, and outcome of vasculitis secondary to immunoadsorption treatment is not known. METHODS: The authors describe a 57-year-old woman with rheumatoid arthritis (RA) resistant to methotrexate and etanercept, who developed severe leukocytoclastic vasculitis after the 9th weekly treatment with Prosorba column. She developed rapidly progressive crescentic glomerulonephritis and required treatment with cyclophosphamide and high-dose prednisone. Subsequently, renal function stabilized and RA remitted. Through the literature search and by reviewing information submitted to Cypress Biosciences Inc (manufacturer of Prosorba columns), available world literature on vasculitis secondary to Prosorba column treatment was compiled. RESULTS: Immune complex deposition of staphylococcal Protein A (SPA)/SPA antibodies in the glomeruli precipitated the renal disease in our patient. Twenty cases of vasculitis (calculated prevalence, 1 per 400), 5 with internal organ involvement, have been reported in patients treated with Prosorba column for thrombocytopenic purpura. Seven RA patients treated with Prosorba column developed vasculitis (prevalence, 7 per 400), 3 with internal organ involvement. CONCLUSIONS: Vasculitis secondary to staphylococcal Protein A immunoadsorption therapy occurs rarely and appears to be related to development of SPA/SPA antibody immune complexes. Rheumatologists should be aware of this potentially serious complication of the Prosorba column treatment for RA. | |
15743468 | Chemokine receptors in the rheumatoid synovium: upregulation of CXCR5. | 2005 | In patients with rheumatoid arthritis (RA), chemokine and chemokine receptor interactions play a central role in the recruitment of leukocytes into inflamed joints. This study was undertaken to characterize the expression of chemokine receptors in the synovial tissue of RA and non-RA patients. RA synovia (n = 8) were obtained from knee joint replacement operations and control non-RA synovia (n = 9) were obtained from arthroscopic knee biopsies sampled from patients with recent meniscal or articular cartilage damage or degeneration. The mRNA expression of chemokine receptors and their ligands was determined using gene microarrays and PCR. The protein expression of these genes was demonstrated by single-label and double-label immunohistochemistry. Microarray analysis showed the mRNA for CXCR5 to be more abundant in RA than non-RA synovial tissue, and of the chemokine receptors studied CXCR5 showed the greatest upregulation. PCR experiments confirmed the differential expression of CXCR5. By immunohistochemistry we were able to detect CXCR5 in all RA and non-RA samples. In the RA samples the presence of CXCR5 was observed on B cells and T cells in the infiltrates but also on macrophages and endothelial cells. In the non-RA samples the presence of CXCR5 was limited to macrophages and endothelial cells. CXCR5 expression in synovial fluid macrophages and peripheral blood monocytes from RA patients was confirmed by PCR. The present study shows that CXCR5 is upregulated in RA synovial tissue and is expressed in a variety of cell types. This receptor may be involved in the recruitment and positioning of B cells, T cells and monocytes/macrophages in the RA synovium. More importantly, the increased level of CXCR5, a homeostatic chemokine receptor, in the RA synovium suggests that non-inflammatory receptor-ligand pairs might play an important role in the pathogenesis of RA. | |
15228844 | Efficacy of cyclosporin-A in refractory rheumatoid arthritis. | 2004 Mar | OBJECTIVE: The aim of the study was to evaluate the efficacy of cyclosporin-A in patients of rheumatoid arthritis not responding to standard therapy early in the course of the disease. DESIGN: A non-randomized controlled clinical trial. PLACE AND DURATION OF STUDY: Outpatients Department of Abbasi Shaheed Hospital and Imam Clinic over a period of 18 months from March 1999 through September 2000. MATERIALS AND METHODS: The study was carried out on 63 patients of both gender suffering with refractory rheumatoid arthritis for at least 3 months. Patients were divided into two groups A and B. Group-A was the experimental one, treated with cyclosporin-A in combination with methotrexate while Group-B was continued with methotrexate alone. Their pre and post assessments regarding recovery criteria and drug profile had been done in order to establish the efficacy of cyclosporin-A. RESULTS: The study showed a significant difference (p<.000 with a.05) after six months between treatment group and the controls, in the mean values of articular index (2.53 vs. 5.39), right grip (14.28 vs. 33.8 mmHg ), left grip strengths (16.5 vs. 34.31 mmHg) and number of tender joints (26.9% vs. 38.6%). Furthermore, a significant negative correlation between articular index at recruitment and visual analogue scale (VAS) of pain after 6 months of therapy was observed in experimental group. CONCLUSION: This study indicates that the combination of cyclosporin with methotrexate benefits rheumatoid arthritis patients refractory to methotrexate monotherapy. Cyclosporin was well tolerated by those having shorter duration of disease. | |
14730601 | Vitamin D intake is inversely associated with rheumatoid arthritis: results from the Iowa | 2004 Jan | OBJECTIVE: Vitamin D is a potent regulator of calcium homeostasis and may have immunomodulatory effects. The influence of vitamin D on human autoimmune disease has not been well defined. The purpose of this study was to evaluate the association of dietary and supplemental vitamin D intake with rheumatoid arthritis (RA) incidence. METHODS: We analyzed data from a prospective cohort study of 29,368 women of ages 55-69 years without a history of RA at study baseline in 1986. Diet was ascertained using a self-administered, 127-item validated food frequency questionnaire that included supplemental vitamin D use. Risk ratios (RRs) and 95% confidence intervals (95% CIs) were estimated using Cox proportional hazards regression, adjusting for potential confounders. RESULTS: Through 11 years of followup, 152 cases of RA were validated against medical records. Greater intake (highest versus lowest tertile) of vitamin D was inversely associated with risk of RA (RR 0.67, 95% CI 0.44-1.00, P for trend = 0.05). Inverse associations were apparent for both dietary (RR 0.72, 95% CI 0.46-1.14, P for trend = 0.16) and supplemental (RR 0.66, 95% CI 0.43-1.00, P for trend = 0.03) vitamin D. No individual food item high in vitamin D content and/or calcium was strongly associated with RA risk, but a composite measure of milk products was suggestive of an inverse association with risk of RA (RR 0.66, 95% CI 0.42-1.01, P for trend = 0.06). CONCLUSION: Greater intake of vitamin D may be associated with a lower risk of RA in older women, although this finding is hypothesis generating. |