Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 8480342 | Thymectomy as treatment of autoimmune diseases other than myasthenia gravis. | 1993 Feb | This paper reviews the different series of thymectomies performed in patients with autoimmune diseases other than myasthenia gravis. It is possible that thymectomy can decrease the activity of T-helper lymphocytes or, alternatively, it may enhance the activity of T-suppressor lymphocytes, whose function is depressed in autoimmune diseases. Thymectomy was performed empirically for systemic lupus erythematosus and rheumatoid arthritis. The therapeutic benefits were questionable. Conflicting results were reported for thymectomy against autoimmune hemolytic anemia. Several trials were conducted to assess the therapeutic value of thymectomy in multiple sclerosis. Benefits were achieved only in relapsing-remitting but not in chronic-progressive multiple sclerosis. The effect of thymectomy in autoimmune diseases associated with myasthenia gravis were also reported. The authors conclude that thymectomy as treatment for autoimmune diseases other than myasthenia gravis is not elective therapeutic choice and it is acceptable only in selected cases. | |
| 8885334 | Enhanced mitochondrial radical production in patients which rheumatoid arthritis correlate | 1996 Aug | Mitochondrial dysfunction contributes to cell damage in a number of human diseases. One significant mechanism by which mitochondria damage cells is by producing reactive oxygen species from the respiratory chain. In this study we measured the production of reactive oxygen species by leukocyte mitochondria in blood from rheumatoid arthritis patients. To do this we used the chemiluminescence of lucigenin, which is accumulated by mitochondria within cells and reacts with superoxide to form a chemiluminescent product. By using specific inhibitors we could distinguish between the production of reactive oxygen species by mitochondria and by NADPH oxidase. There was a five-fold increase in mitochondrial reactive oxygen species production in whole blood and monocytes from patients with rheumatoid arthritis, when compared to healthy subjects or patients with non-rheumatic diseases. There was no increases in mitochondrial reactive oxygen species production by neutrophils from rheumatoid arthritis patients. The enhanced mitochondrial radical production in rheumatoid arthritis patients correlated significantly with increased levels of tumor necrosis factor alpha in plasma (p < 0.0001). As tumor necrosis factor alpha is known to increase mitochondrial reactive oxygen species production the elevated mitochondrial radical formation seen in rheumatoid arthritis patients may be due to activation of the mitochondrial radical production. These data suggest that elevated mitochondrial oxidative stress contributes to the pathology of rheumatoid arthritis. | |
| 1598498 | A human monoclonal IgA rheumatoid factor using the VkIV light chain gene. | 1992 | A human hybridoma stably secreting IgA rheumatoid factor (RF) was produced by cell hybridization with peripheral blood lymphocytes of a patient with rheumatoid arthritis. The RF was of the IgA1 isotype with kappa-light chains and was useful for standardization or specificity controls in class-specific RF assays. RF activity was detected only when the IgA molecular were in a polymeric state, and could be measured by enzyme linked immunosorbent assay as well as in conventional agglutination based tests. The RF had the modified Ga fine specificity described previously for several RFs and for protein A. The immunoglobulin V genes used were isolated and sequenced. The light chain was encoded by the VkIV gene rearranged to Jk2; compared to the published VkIV germ line gene there was 90% nucleotide homology. The heavy chain gene used belonged to the VHI family and was rearranged to JH4. Comparisons with published sequences revealed 90% homology with the recently characterized VH gene expressed by RF-TS3, a rheumatoid synovia RF hybridoma. | |
| 7836783 | Difference and ratio plots: simple tools for improved presentation and interpretation of s | 1995 Jan 27 | 11111onglutinin-binding assay (KgBa) has gained widespread use for the detection of circulating immune complexes. A recent paper questioned the interpretation of the results obtained by this method and the validity of the assay (Holmskov et al. (1992) J. Immunol. Methods 148, 225). We now present hitherto unnoted differences between controls and patients with either rheumatoid arthritis or systemic lupus erythematosus. For this we use simple, but unconventional, graphic representations of the data, based on difference plots and ratio plots. Differences between patients with Burkitt's lymphoma and systemic lupus erythematosus from another previously published study (Macanovic, M. and Lachmann, P.J. (1979) Clin. Exp. Immunol. 38, 274) are also represented using ratio plots. Our observations indicate that analysis by regression analysis may often be misleading. | |
| 8056050 | Clonal expansions of V delta 1+ and V delta 2+ cells increase with age and limit the reper | 1994 Aug | We have investigated the complexity of the human gamma delta T cell repertoire by means of a VJ heteroduplex analysis method. cDNA obtained from peripheral blood mononuclear cells was amplified with V delta 1-C delta or V delta 2-C delta primers. The product was denatured and renatured to allow random reannealing of the strands and the heteroduplexes carrying mismatched junctional sequences were separated from the homoduplexes on polyacrylamide gels. Whenever one or more T cell clones were expanded to over 10% of the polyclonal background, discrete bands of homo- and heteroduplex appeared. This method was applied to the analysis of the peripheral gamma delta compartment from healthy donors and rheumatoid arthritis patients of different ages. While samples from young individuals showed a polyclonal pattern, a clear tendency towards oligoclonality appeared with increasing age, both in normal individuals and rheumatoid arthritis patients. We also show that the VJ junctional sequence derived from the heteroduplex fragments can be successfully used to isolate and characterize the corresponding T cell clones in vitro, even after a period of 1 year. In conclusion, our findings indicate that the complexity of the gamma delta T cell repertoire decreases with age as a consequence of the expansion of a few T cell clones. | |
| 8192967 | Dynamic gadolinium-enhanced MR imaging in active and inactive immunoinflammatory gonarthri | 1994 May | Dynamic T1-weighted FLASH MR imaging, obtained just after i.v. gadopentetate dimeglumine injection, and pre- and postcontrast T1-weighted spin-echo (T1-SE) MR imaging were performed to compare their information value with respect to inflammatory activity in immunoinflammatory gonarthritis. We examined 16 clinically active (CAG), 7 clinically inactive (CIG) and 4 healthy knees. The synovium of a preselected slice was outlined. Its area and relative signal intensity increase after gadopentetate dimeglumine on T1-SE and FLASH (at each time t) were calculated. The CAG knees showed a mean signal intensity increase on early dynamic FLASH images higher by far than the CIG knees, while no significant difference was found on spin-echo images obtained 5 to 15 min after contrast injection. The early signal enhancement probably reflects the perfusion and capillary permeability of the synovium. The area of synovium could differentiate between healthy and arthritic knees. Gadolinium-enhanced dynamic FLASH imaging may provide clinically useful information about the actual inflammatory activity of arthritic joints. | |
| 8081663 | Collagen arthritis--what can it teach us? | 1994 Sep | Collagen-induced arthritis is an arthritic disease that can be induced in rodents and primates. It is used widely as a model of disease processes and potential therapies. The immunology of collagen arthritis has some compelling parallels with human disease and these have been exploited recently in several novel ways to analyse the nature of autoreactivity against joint antigens and to test new therapies. Antibodies against lymphocyte surface markers, such as CD4, CD40L and MHC Class II, have been shown to suppress disease progression. Manipulation of cytokines, notably TNF-alpha, IL-1 and IL-2, has been extensively studied using the cytokines themselves, antibodies against cytokines and other antagonists with varied, but promising results. The search for antigen-specific immunosuppression has gained new impetus through manipulation of collagen arthritis by mucosal delivery of collagen to induce tolerance that suppresses disease. This review examines the salient features of collagen arthritis that are relevant to human disease and discusses the meaning and potential application of experimental therapies to the control of human arthritis. | |
| 7801197 | [Expression of adhesion molecules, intercellular molecule (ICAM)-1 and lymphocyte function | 1994 Oct | We histochemically examined the expression of adhesion molecules, ICAM-1 and LFA-1, of endothelial cells in the synovial tissues of rheumatoid arthritis. Subjects were 7 RA patients of 1, 3, 4 months and 2, 3, 5, 7 years duration, 2 cases of mixed connective tissue disease (MCTD), both of 5 years duration, and 3 cases of osteoarthritis (OA) 15 years after onset. ICAM-1 was expressed on the cell surface and in the cytoplasm of the endothelial cells of small veins, and in the germinal center of lymphoid follicle, while LFA-1 was expressed on lymphocytes around the small vessels which expressed the ICAM-1 molecule. The most characteristic point of this study was that we adopted not only histochemical but also quantitative methods. At one month from onset, faintly positive ICAM-1 molecules were expressed on endothelial cells accompanied by LFA-1 positive spindle cells, called interstitial cells. Typical high endothelial venules (HEV) with intensive expression of ICAM-1 appeared 3 months after onset. These LFA-1 positive lymphocytes consisted of equal numbers of CD4+ and CD8+ T lymphocytes. There were few B lymphocytes in the synovial tissues in the early stage. The number of small vessels expressing ICAM-1 decreased with the development of the lymphoid follicle, though the intensity of ICAM-1 expressed in each vessel was very high. Our data revealed that ICAM-1 was expressed not only in RA synovia but also in OA which is not ordinarily considered to be immunogenic inflammation, though the molecules were expressed on the flat endothelial cells and not HEV, without accumulation of lymphocytes.(ABSTRACT TRUNCATED AT 250 WORDS) | |
| 1361078 | Oligoclonal T cells in rheumatoid arthritis: identification strategy and molecular charact | 1992 Dec | Immunodominant antigens in rheumatoid arthritis (RA) should induce an expansion of T cells bearing a corresponding T-cell receptor (TCR). We therefore analysed the TCR repertoire at the site of inflammation using two fundamentally different strategies. The total TCR repertoire was examined by generating 'representative' T-cell clone panels, which were subsequently tested for clonality by restriction mapping of the TCR beta gene locus. No clonality was detected in large T-cell clone panels generated with cells from three patients. However, when we selectively analysed the TCR repertoire of in vivo pre-activated, interleukin-2 (IL-2)-responsive T cells, significant T-cell/TCR clonality was found in 2 out of 4 patients. The clonal T cells represented a minority of the total T-cell population with an estimated frequency of 1 in 300 to 1 in 1000 cells. Molecular characterization of a clonal TCR and the use of a specific TCR V beta MoAb ruled out an over-representation of T cells bearing the same V beta element in the total T-cell population, rendering the involvement of super-antigens in the induction of T-cell clonality in this case unlikely. | |
| 1439483 | Interleukin-8 in inflammatory rheumatic diseases: synovial fluid levels, relation to rheum | 1992 | The content of interleukin-8 (IL-8) in the synovial fluid and its production by blood and synovial fluid mononuclear cells (PBMC and SFMC) was compared in rheumatoid arthritis (RA) and various other inflammatory rheumatic disorders. The study included 125 patients and 20 healthy individuals. The highest concentrations of IL-8 were found in the synovial fluids and culture supernatants of PBMC and SFMC from patients with seropositive RA. Only PBMC from seropositive patients, and not from other rheumatic diseases, exhibited significant spontaneous release of IL-8 that correlated with serum IgM rheumatoid factor titers. Gold sodium thiomalate (GST) and methotrexate (MTX) inhibited the spontaneous and stimulated IL-8 production by PBMC by 55-86% at 50 and 10 micrograms/ml, respectively. Two main conclusions were drawn: (1) rheumatoid factors appeared to be a major cause of enhanced IL-8 production in seropositive RA, and (2) inhibition of IL-8-mediated neutrophil migration and activation could be part of the mechanism of action of GST and MTX. | |
| 7507728 | Increased frequency of NGF in sera of rheumatoid arthritis and systemic lupus erythematosu | 1993 Dec 13 | Nerve growth factor (NGF) levels were measured by a two-site enzyme-linked immunosorbent assay (ELISA) in sera of patients with three autoimmune diseases, rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and thyroiditis. Serum NGF levels were variable (15 pg ml(-1)-1.6 ng ml-1) but not significantly different among these groups compared with control subjects. However the frequency of detectable circulating NGF was significantly higher in RA and SLE patients but not in thyroiditis patients compared with controls. The present data provides evidence for NGF involvement in two autoimmune rheumatic diseases and suggests a possible differential role of NGF as immunomodulatory agent in systemic versus certain organ-specific autoimmune diseases. | |
| 8844499 | Intravenous cyclophosphamide combined with methylprednisolone in the treatment of severe r | 1996 Jul | The mode of action of methylprednisolone and cyclophosphamide in the treatment of rheumatoid arthritis still remains unclear. We sought to determine whether methylprednisolone and/or cyclophosphamide affect surface antigens on peripheral blood lymphocytes. Twenty-eight patients with severe refractory rheumatoid arthritis were observed for 12 months. Thirteen patients were treated with an intravenous pulse of methylprednisolone, and fifteen with methylprednisolone combined with cyclophosphamide. The surface antigens of lymphocytes and natural killer (NK) cells isolated from peripheral blood were determined using flow cytometry. The clinical improvement was observed in 16 (57%) patients (8 treated with methylprednisolone and 8 with methylprednisolone/cyclophosphamide). However, after cessation of the treatment in 9 patients, a flare up of the disease was observed. A striking decrease in total lymphocyte count was observed. The percentage of CD3+ and CD3+CD4+ cells remained unchanged. We observed a decrease in the percentage of CD3+CD8+ in patients treated with methylprednisolone/cyclophosphamide. Moreover, the percentage of activated T cells (CD25+ cells and HLA-DR+ cells) was reduced. The depletion of CD8+CD25+ cells was observed after combined treatment. The percentage of CD19+CD5+ was reduced due to the treatment. We also observed a decrease in CD16+CD56+ NK cells. Amelioration of the course of the refractory rheumatoid arthritis was observed in patients treated with both methylprednisolone and methylprednisolone/cyclophosphamide. A stronger effect on lymphocyte phenotype was observed in those given methylprednisolone/cyclophosphamide, but it was not followed by further benefit. On the other hand, the clinical improvement was more stable in methylprednisolone/cyclophosphamide-treated patients. The use of cyclophosphamide should be reserved for patients with rapidly progressing rheumatoid arthritis or life-threatening complications. | |
| 7680551 | Localisation of vitronectin receptor immunoreactivity and tartrate resistant acid phosphat | 1993 Feb | The influx of cells into the synovial intima in rheumatoid joints may include osteoclasts and their precursors. The distribution of osteoclast markers--namely, tartrate resistant acid phosphatase activity and the expression of vitronectin receptor (shown with monoclonal antibodies 13C2 and 23C6)--was therefore examined in synovium obtained from patients with rheumatoid (RA) or degenerative (OA) arthritis. Tartrate resistant acid phosphatase positive cells were found in frozen sections of 60% (n = 30) of RA and 69% (n = 29) of OA synovial membranes. Whereas all synovia tested (four RA, four OA) showed diffuse staining of the lining cells with 13C2, 55% (n = 11) of RA and 57% (n = 14) of OA synovial membranes contained isolated cells stained with 23C6 scattered throughout the tissue. In cultures of synovial cells, tartrate resistant acid phosphatase positive, multinuclear, and 23C6 positive cells were found; these cells did not, however, form resorption pits on bone slices. The results show that fully differentiated osteoclasts are uncommon in synovium from patients with either degenerative or inflammatory arthropathies. | |
| 7540206 | Expression of estrogen receptor related protein (p29) and estradiol binding in human arthr | 1995 Mar | OBJECTIVE: We investigated the expression of estrogen receptors (ER) and the presence of estradiol in human synovial tissues from subjects without arthritis and patients with traumatic arthritis, osteoarthritis, and rheumatoid arthritis. METHODS: Synovial tissues were immunostained using ER-D5 monoclonal antibody (Mab) directed toward an ER related protein (p29), ER-ICA Mab directed toward nuclear ER, and antiestradiol serum. Fluorescent estradiol was used to demonstrate specific estradiol binding to ER. RESULTS: (1) p29 was present predominantly in hyperplastic synovial lining cells and smooth muscles of blood vessels. (2) Exogenous estradiol bound to synoviocytes and sublining macrophage-like cells in the inflamed synovium. (3) Endogenous estradiol was also detected in hyperplastic lining cells and macrophage-like cells in arthritic synovium. CONCLUSION: Our study demonstrated the expression of ER in arthritic synovium and suggested that estrogen modulates local inflammation in various joint diseases via synoviocytes as well as sublining macrophage-like cells. | |
| 8050232 | Cruciate retained and excised total knee arthroplasty. A comparative study in patients wit | 1994 Aug | A comparative study of posterior cruciate ligament retention and excision was conducted in patients who underwent bilateral total knee arthroplasty using the total condylar modifier prosthesis. The posterior cruciate ligament was excised in one knee and was retained in the other knee in 28 patients. Postoperative results were assessed using the Hospital for Special Surgery Knee Evaluation Score. In addition, stair activity was tested to determine whether there was preferential dependence on one of the two knees. There was no significant difference between the posterior cruciate ligament retained or excised knees in terms of postoperative Hospital for Special Surgery Knee Evaluation Score. Patients who ascended and descended stairs with one leg at a time tended to prefer the posterior cruciate ligament retention side. Those who could use each leg in sequence to go up and down stairs, however, did not show preferential dependence on either knee. | |
| 7534432 | Increased soluble endothelial adhesion molecules in rheumatoid arthritis correlate with ci | 1995 Mar 4 | Endothelial cells express adhesion molecules and release free forms (e.g., sELAM-1, sGMP-140, sICAM-1 and sVCAM-1). Compared with controls, the serum levels of these soluble adhesion molecules (SAM) were significantly increased in patients with rheumatoid arthritis. We investigated whether this was associated with the circulating cytokines and changes in peripheral blood T-lymphocyte (T-PBL) subsets. In healthy subjects, sELAM-1 correlated with the serum levels of Il-1 beta, Il-1 receptor antagonist (Il-1RA) and Il-6, while sGMP-140 was associated with Il-8, and sVCAM-1 was related to Il-7 and Il-8. Thus, already in controls, relations exist between the levels of SAM and circulating cytokines. The rheumatoid arthritis patients with low and high serum levels of IgA- and/or IgM-rheumatoid factors (RF) were separately analyzed. They have different cytokine profiles and showed distinct correlations. In patients with low RF, sGMP-140 and sVCAM-1 correlated with Il-1 beta, while sICAM-1 was associated with Il-7 and TNF-alpha. In patients with high RF, sELAM-1 correlated with Il-1RA, and sGMP-140 was associated with many cytokines (e.g., GM-CSF, MIP-1 alpha and TNF-alpha). In addition, lymphopenia (less than 1000 lymphocytes/microliters) was shown in 30% of the patients, and 20% (mostly with low RF levels) had reduced levels of "primed" CD45RO+ cells among T-PBL. In controls, cytokines (Il-7, Il-8 and GM-CSF), but not SAM, were associated with less CD45RO+ T-PBL. In patients with low RF only, sGMP-140 and sELAM-1 correlated with the depletion of "primed" CD4+ and CD8+ T-PBL respectively. In such patients, Il-1 beta and GM-CSF also correlated with less CD8+, CD45RO+ T-PBL. Thus, particularly in patients with low RF, increased SAM, possibly released by the endothelial cells, might reflect the cytokine-induced activation of the vascular endothelium and the extravasation of some CD45RO+ T-PBL. | |
| 7490601 | Validation of a meta-analysis: the effects of fish oil in rheumatoid arthritis. | 1995 Nov | The purpose of this study was to validate the results of a meta-analysis showing the efficacy of fish oil in rheumatoid arthritis with the results of a re-analysis of the complete primary data set. A Medline search yielded seven published papers. Three additional trials were found by contacting authorities in the field. Inclusion criteria included (1) a double-blind, placebo-controlled study, (2) use of at least one of seven predetermined outcome measures, (3) results reported for both placebo and treatment groups at baseline and follow-up, (4) randomization, and (5) parallel or cross-over design. Papers were scored for quality. Demographic and outcomes variables were collected. For the re-analysis of the primary data, the same variables were abstracted for the 395 individual patients randomized. The meta-analysis demonstrated that dietary fish oil supplementation for 3 months significantly reduced tender joint count (rate difference [RD] [95% CI] = -2.9 [-3.8 to -2.1] [p = 0.001]) and morning stiffness (RD [95% CI] = -25.9 [-44.3 to -7.5] [p < 0.01]) as compared with heterogeneous dietary control oils. The re-analysis of the primary data confirmed a significant reduction in tender joint count (p = 0.001) and in morning stiffness (p < 0.02) in the parallel analysis that ignored interaction terms. The analyses that included an interaction term between site and treatment again confirmed a significant reduction in tender joint count. The results for morning stiffness were similar to the meta-analysis, but did not quite reach statistical significance (p = 0.052-0.083). The relative improvements in the other outcome variables did not reach statistical significance. Use of fish oil improved the number of tender joints and duration of morning stiffness at 3 months as analyzed by both meta- and mega-analysis. The fuller mega-analysis confirmed the results of the meta-analysis. The advantages of mega-analysis were as follows: (1) the ability to analyze the homogeneity of the patient populations, (2) the ability to make clinically sensible adjustments in the form of the comparison, and (3) the ability to examine subsets of the data. | |
| 7980751 | An evaluation of the effectiveness, safety and acceptability of a nurse practitioner in a | 1994 Mar | Seventy patients with RA were randomly allocated to either a Rheumatology Nurse Practitioner (RNP) or Consultant Rheumatologist (CR) clinic. They were seen on six occasions in 1 year. Effectiveness and safety were assessed by biochemical, clinical, psychological and functional variables; patient knowledge and satisfaction were measured by questionnaire. At week 0 the groups were well matched clinically and demographically. By week 48 significant improvements had occurred in plasma viscosity and articular index within both groups. In patients managed by the RNP, pain, morning stiffness, psychological status, patient knowledge and satisfaction had all improved significantly (P = 0.001; P = 0.028; P = 0.0005; P < 0.0001; P < 0.0001 respectively), improvements not mirrored by the CR cohort. Between group comparisons also showed significant differences by the end of the study. Compared to the CR patients, the RNP suffered from lower levels of pain (P < 0.05), had acquired greater levels of knowledge (P < 0.0001) and were significantly more satisfied with their care (P < 0.0001). | |
| 1483619 | [Ibuprofen--successful in activated arthrosis. Results of a administration study]. | 1992 Dec 10 | Within the framework of an observational study carried out on a national basis and involving some 4,000 patients, a total of 1,156 patients with activated arthrosis were treated with oral ibuprofen and observed over a period of three weeks. It was found that, at a dose of 600 mg tid, ibuprofen led to significant remission rates in terms of the symptoms pain at rest, pain on movement, tenderness, restriction of movement, swelling, joint effusion, and morning stiffness. After the third week of treatment, these rates reached 90%. In the first week, rapid onset of action within the first 30 minutes was noted in about 50%, which increased in the third week to 65%. Since at the same time the tolerability of ibuprofen was also found to be good--4% side effects--it can be recommended also for long-term use in this indication. | |
| 7869324 | A novel autoantibody to the putative oncoprotein DEK in pauciarticular onset juvenile rheu | 1994 Nov | OBJECTIVE: To define the frequency of a novel autoantibody reactive with a 45 kDa protein in children with juvenile rheumatoid arthritis (JRA). This protein is expressed by the putative oncogene DEK associated with a subtype of acute myeloid leukemia. METHODS: The sera of 158 children with JRA were analyzed for the presence of anti-DEK by immunoblotting using purified DEK protein and compared with sera of 109 children with other rheumatic diseases and 25 healthy controls with no connective tissue disease. RESULTS: Antibodies to DEK were found significantly more frequently among children with JRA than among children with other rheumatic diseases or controls (p < 0.001). Among children with JRA, anti-DEK was significantly more often associated with pauciarticular onset than with poly-articular and systemic onset subtypes (77 vs 29 and 8%, respectively, p < 0.001). Anti-DEK was no more frequent among children with pauciarticular JRA complicated by iritis than among those without iritis (88 vs 71%, respectively). The frequency of anti-DEK in other rheumatic diseases varied from 0 in children with spondyloarthritis to 31% in scleroderma. CONCLUSION: Antibodies to DEK are highly associated with pauciarticular onset JRA. |