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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
8036521 Low-dose methotrexate in rheumatic diseases--efficacy, side effects, and risk factors for 1994 Apr Controlled trials and observational studies have shown low-dose methotrexate (MTX) to be a second-line agent of high potency with a favorable profile of safety and tolerability in the treatment of rheumatoid arthritis (RA). Its risk-benefit ratio in psoriatic arthritis is less well documented. Preliminary reports on its beneficial effects in other disorders, including the systemic manifestations of RA, other spondyloarthritides, and collagen vascular diseases, merit more detailed examination. Gastrointestinal intolerance and hepatic enzyme elevation are the most frequent side effects of MTX; life-threatening events such as severe hemocytopenia and MTX pneumonitis are rare and amenable to prevention by recognizing risk factors and premonitory signs. Hepatotoxicity does not appear to be a major limiting factor in RA patients over the first 2 to 3 years of MTX therapy; its impact on long-term tolerance remains to be clarified.
9033614 [Non-cancer uses of methotrexate]. 1996 Dec 14 Methotrexate, used for nearly 40 years as an antimetabolite for cancer therapy, also has indications in dermatology, rheumatology and pneumology. When given at low dosage, it has an antiinflammatory effect although the mechanism is not totally understood. Numerous therapeutic trials have been performed in chronic inflammatory diseases such as rheumatoid arthritis in the adult, juvenile polyarthritis and corticosteroid-dependent asthma. Methotrexate is effective in severe resistant forms of rheumatoid arthritis and is used either alone or in combination with other drugs as first intention therapy because of the good tolerance, patient compliance and ease of use. The beneficial effect in severe corticosteroid-dependent asthma remains to be demonstrated. It has also been used in severe forms of psoriasis and may be useful in other diseases with an autoimmune component. Other less common indications including Crohn's disease, ectopic pregnancy and pregnancy termination require confirmation. Tolerance and compliance are generally good, even for prolonged treatments and undesirable effects are almost always reversible at withdrawal.
1280845 Population genetics of rheumatoid arthritis. 1992 Nov A major component of genetic susceptibility to rheumatoid arthritis (RA) appears to be explained by inheritance of HLA-DRB1 alleles, which have a conserved sequence of amino acids in the third hyper-variable region of the molecule. This "shared epitope" is found on various DR4, DR1, and DR6 variants, as well as on DR10. The evidence for this "shared epitope" in RA is examined at the population level, including how it fits in with the available epidemiologic data and RA disease severity.
1362229 [Possible role of cellular immunity against tubular basement membrane antigen (TBM) in gol 1992 Jun Autoantibody formation and lymphocytes proliferative response to tubular basement membrane (TBM) antigen were examined to clarify the pathogenesis of gold nephropathy, in rheumatoid arthritis patients. The existence of tubulopathy was ascertained by urine protein analysis, electrophoresis and urine TBM antigen titration. Circulating antibody to human TBM antigen titrated by enzyme immunoassay was significantly elevated in patients with gold tubulopathy, and mitogenic stimulation with TBM antigen of peripheral lymphocytes specifically responded in the early stage after receiving gold, but then clearly decreased after the cessation of gold. But, when the lymphocytes had been passed through a nylon wool column, the reaction was remarkably high even in the later stage after receiving gold, suggesting that another suppressive population of lymphocytes became trapped in the nylon wool column. This evidence suggests that gold compounds definitely act as initiating and promoting agents, and the development of tubular disorders induced by gold are likely related to the cellular recognition of effector T cells to the TBM antigen, following the strong effect of gold on the cellular immune system.
8786919 The value of skeletal scintigraphy in predicting the need for revision surgery in total kn 1996 Apr We have reviewed the results of 99mtech-netium-methylene diphosphonate (Tc-MDP) bone scintigrams performed on patients following total knee arthroplasty. In addition, 67gallium (Ga) citrate scintigrams were carried out sequentially on 29 patients. Three groups of patients were identified: those with asymptomatic knees (undergoing scans for other reasons); those with aseptic or septic loosening; and those with pain without radiologic evidence of loosening. There was good correlation between the results of the scans and the final outcome. We conclude that sequential 99mTc-MDP and 67Ga citrate scintigrams are useful for demonstrating the presence of aseptic and septic loosening in knee prostheses, and pain with a normal scan appearance is probably not due to loosening or infection.
7782653 [Results after cemented total knee arthroplasty: a follow-up study over 5-to-14 years]. 1995 Apr Eighty-five cemented total knee arthroplasties were followed for five to fourteen years (mean 7.8 years). The clinical evaluation was excellent or good in 85% of this series. However, a complication developed in 15 knees (17.6%), and two thirds of these complications were found in the patello-femoral joint. One further case developed an infection (1.2%), and four others (4.7%) developed an aseptic loosening. Over all, 8 cases (9.4%) required revision surgery. Asymptomatic wear was seen to progress in some implants involving thin polyethylene, although their clinical results were rated as excellent. The outcome of the cemented knee arthroplasties was considered as acceptable at present, but improved surgical techniques and measures against polyethylene wear are required for future improvement in this surgery.
8919618 Use of titanium grommets in silicone implant arthroplasty of the hallux metatarsophalangea 1996 Mar Double-stem silicone implants protected by titanium grommets were placed in the hallux metatarsophalangeal joints of 32 patients (47 feet). All patients had a painful destroyed joint and most were women. Three patients (six feet) were lost to follow-up. Nineteen patients had a diagnosis of rheumatoid arthritis (25 feet) and 10 had degenerative joint disease (16 feet). The average age for the group was 57 years and the average follow-up was 51 months (range, 34-76 months). Twenty patients (30 feet) were completely satisfied with their result. Eight patients (10 feet), all with rheumatoid arthritis, had some minor postoperative complaints, usually involving the lateral toes. Two patients (three feet) in this group had no pain, but would have preferred more hallux motion. One patient with rheumatoid arthritis (one foot) had a poor result due to implant removal for deep sepsis. Radiographic analysis of these patients showed no evidence of implant fracture and the implant composite appeared to be well tolerated by the surrounding bone in which it was placed. When compared with another, similar group of patients in whom grommets were not used, this implant appeared to be much more stable, as there was significantly less evidence of radiolucency seen around those implants protected by the grommets. It appears that the titanium grommets may protect the silicone implant and may help provide a longer life for the silicone implant.
7728398 Rheumatoid factor associated with a secretory component in rheumatoid arthritis. 1995 Mar The authors' objective was to study the serum secretory immunoglobulin A (S-IgA) concentration and the presence of rheumatoid factor (RF) complexed with a secretory component (SC) in rheumatoid arthritis (RA). Sixty-three RA patients were studied. There were 49 healthy subjects in the control group. The S-IgA concentration and the presence of IgA isotype RF were determined by ELISA in the serum. The presence of SC complexed to RF (SC-RF) was studied by a sandwich-type enzyme-linked immunosorbent assay with an antibody against the SC used to capture S-immunoglobulin, and associated anti-globulin activity was revealed with a peroxidase-conjugated human IgG Fc fragment. We observed a significant increase in S-IgA in RA (mean 76.8 micrograms/ml +/- 152.9 S.D.), as compared to controls (mean 13.6 micrograms/ml +/- 11.9 S.D.) (P < 0.01). Forty-one per cent of RA patients presented a S-IgA concentration above the upper threshold, but we did not observe any association with disease activity. S-IgA concentration was correlated with the presence of IgA-RF. Twenty-seven RA patients had a positive SC-RF versus one in the control group (P < 0.01). The presence of SC-RF was associated with an increased S-IgA concentration (P < 0.0001), and the presence of RF-IgA (P < 0.002). However, no association with disease activity was noted. Our study showed that serum S-IgA was increased in RA, and that part of the RF were complexed with SC. These results suggest contribution of mucosal lymphocytes in the pathogenesis of RA.
8909250 Synovial fibroblasts of patients with rheumatoid arthritis attach to and invade normal hum 1996 Nov Rheumatoid arthritis (RA) has been thought to be largely a T-cell-mediated disease. To evaluate the role of T-cell-independent pathways in RA, we examined the interaction between isolated RA synovial fibroblasts and normal human cartilage engrafted into SCID mice in the absence of T cells and other human cells. The expression of cartilage-de grading enzymes and adhesion molecules was examined by immunohistochemistry and in situ hybridization techniques. The RA synovial fibroblasts invaded the cartilage and kept their transformed appearing cellular shape. They expressed VCAM-1 and produced the cathepsins L and B at the site of invasion. We conclude that RA synovial fibroblasts maintain their invasive and destructive behavior over longer periods of time in the absence of human T cells, indicating that T-cell-independent pathways play a significant role in rheumatoid joint destruction.
7521808 Expression of the chemokine superfamily in rheumatoid arthritis. 1994 Sep The infiltration of leucocytes into the joint of rheumatoid arthritis (RA) is believed to be mediated by chemotactic factors released by activated cells. In this study, examination was made of the gene expression and production of the chemokine superfamily in RA patients by reverse transcriptase-polymerase chain reaction (RT-PCR) and immunoprecipitation. Cultured synovial fibroblasts were found capable of expressing and producing IL-8, GRO, monocyte chemotactic and activating factor (MCAF), macrophage inflammatory protein-1 alpha (MIP-1 alpha), MIP-1 beta and RANTES in response to IL-1 alpha. The expression of IL-8, GRO, MCAF, MIP-1 alpha, and MIP-1 beta was clearly shown to increase in freshly isolated synovial fluid mononuclear cells (SFMC) of RA patients, in contrast to peripheral blood mononuclear cells (PBMC) of RA patients and normal subjects. The gene expression of RANTES appeared to be the same for RA SFMC, RA PBMC, and normal PBMC. Thus, the over-expression of various chemokines may promote the recruitment of inflammatory cells into rheumatoid inflamed joints.
8565572 Comparative epitope mapping of antibodies to collagen in women with silicone breast implan 1996 Previous work has shown that women with silicone gel breast implants have an increased frequency of autoantibodies to collagen types I and II. 70 women without a specific autoimmune disease, using criteria of the American College of Rheumatology, but who had silicone breast implants were studied for the presence of serum antibodies to native and denatured human types I and II collagen by ELISA. 82 women with systemic lupus erythematosus (SLE), 94 women with rheumatoid arthritis (RA), and 133 healthy controls were also studied. There was a high frequency of autoantibodies to collagen in each of the groups when compared to the healthy controls. The specificities of these antibodies were found to differ markedly when examined by immunoblotting using peptides derived by cyanogen bromide digestion of the collagens. Sera from women with silicone implants reacted with multiple peptides of type I collagen in an individual-specific manner, but sera from women with SLE or RA reacted weakly with a restricted range of peptides. Against type II collagen, sera from women with RA reacted strongly with multiple peptides, while sera from women with silicone implants or SLE reacted only weakly or not at all. The patterns of reactivity against collagens by sera from women with silicone implants suggest that silicone can act as an adjuvant to enhance the immunogenicity of type I collagen.
8923077 An unusual cause for collapse in a patient with arthritis. 1996 Oct We present the clinical case of a patient who was admitted to the intensive care ward with severe central nervous system symptoms and cardiovascular collapse within a week of starting sulphasalazine; in the absence of any other diagnosis, these symptoms were felt to be due to a previously unreported adverse effect of sulphasalazine.
7586984 Antibodies to human immunodeficiency virus (HIV-1) in autoimmune diseases: primary Sjögre 1995 Jul The aetiology of autoimmune diseases remains unknown. The relationship between virus, and more recently retrovirus, has been suggested with this group of diseases. Immunoblotting is a useful method for determining the presence of proteins coded by different retrovirus genes. Since the prevalence of these types of proteins in patients with primary Sjögren's syndrome (SS), systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and autoimmune thyroid diseases has not been fully established, the aim of this work was to determine the prevalence of antibodies to immunodeficiency human virus type 1 (HIV-1) proteins in these diseases and their possible relationship with the presence of anti-nuclear, anti-DNA, anti-SSA (Ro) and anti-SSB (La) autoantibodies. Antibodies to human immunodeficiency virus (HIV-1) were studied in a group of 341 patients with autoimmune diseases (77 SS, 98 SLE, 75 RA, 91 autoimmune thyroid diseases) and 126 blood donors as a control group. A Western blot was used to detect antibodies to HIV-1, and a double polymerase chain reaction (PCR) using nested primers in the gag and pol gene of HIV-1. Antinuclear antibodies, anti-DNA, anti-SSA (Ro) and anti-SSB (La) were determined by enzyme-linked immunosorbent assays. At least one band was shown on immunoblotting in 26% of patients with autoimmune diseases and 35% of controls. The presence of antibodies to p55 or p68 proteins in patients with SS or SLE proved to be the only statistically significant difference between the other autoimmune diseases studied and the control group. These antibodies were not associated with autoantibodies ANA, DNA, SSA (Ro) or SSB (La).(ABSTRACT TRUNCATED AT 250 WORDS)
7677447 Remitting seronegative symmetrical synovitis with pitting oedema: disease or syndrome? 1995 Aug OBJECTIVE: To evaluate the outcome of patients with remitting seronegative symmetrical synovitis with pitting oedema (RS3PE). METHODS: In a retrospective chart review study, we identified all the patients presenting with polyarthritis and pitting oedema in the past 20 years. We tried to recall the 24 patients with characteristics of RS3PE according to McCarty et al. Two patients had died and four could not be traced. Five could not be seen after the initial period of follow up; relevant data were obtained from their practitioner. For the remaining 13 patients, clinical, radiological, and biological evaluation was performed in our department, with the last assessment in 1993. RESULTS: The follow up period was from one to 18 years (mean 4.6 (SD 4.5) years). Eleven patients developed one or several recurrences of articular manifestations consisting of mild oligoarthritis (n = 8), definite spondyloarthropathy (n = 2), and rheumatoid arthritis (n = 1). The delay of the first recurrence was 18 months to 12 years after the first attack. Thirteen patients had no recurrence, but three of them developed remarkable features: rheumatoid factor, antinuclear antibodies (1/2000), Sjögren's syndrome. HLA B typing was performed in nine patients and revealed B7 (n = 2), B27 (n = 2) and B22 (n = 2). Isolated HLA B27 typing was performed in two other patients and was positive in one. CONCLUSION: The long term outcome of RS3PE can lead to different rheumatic diseases. RS3PE appears to be a syndrome related to the elderly onset of the rheumatic diseases, including spondyloarthropathy and rheumatoid arthritis, rather than a specific entity.
8572492 [Cutaneous pseudolymphoma during treatment of rheumatoid polyarthritis with low-dose metho 1995 INTRODUCTION: Over the last three years, there have been over twenty case reports of lymphoma in patients given low-dose methotrexate for rheumatoid arthritis. We observed the first case of cutaneous pseudolymphoma. CASE REPORT: A 56-year-old man had been treated with methotrexate (15 mg/day) for 6 years due to rheumatoid arthritis. He developed three isolated papulonodular ulcerations on the limbs. The histology and immunohistochemical examinations demonstrated T and B lymphoplasmocyte infiltration without epidermotropism nor destruction of the annexes. Immunolabelling for anti-Epstein-Barr virus was negative. There was a IgG lambda type monoclonal hypergammaglobulinaemia, Bence-Jones proteinuria and an increase in beta 2-microglobulin. The thoracoabdominal scan, bone marrow biopsy and gallium scintigraphy were normal. There was no sign of a Gougerot-Sjögren syndrome nor of a Felty syndrome. The skin lesions and the Bence-Jones proteinuria disappeared rapidly after withdrawal of methotrexate. There has been no recurrence with a follow-up of 16 months. DISCUSSION: The diagnosis of pseudolymphoma was retained on the basis of the clinical features, the histological and immunohistochemical evidence and especially on the clinical course after methotrexate withdrawal, i.e. spontaneous regression of the lesions within 3 weeks. A similar course has been observed in three cases of lymphocyte proliferation suggesting that this immunosuppressor would be the most probable causative agent. Lymphocyte proliferation, mainly B-cell lymphomas in haematopoietic organs occurring under methotrexate administration have occurred mainly in patients with rheumatoid arthritis. Three cases have also been described in patients with dermatomyositis, but none have been reported in patients with psoriasis. This would suggest that cofactors involved in these autoimmune diseases could also have an effect: immunodepression, potentialization due to associated treatment (corticosteroids), Epstein-Barr virus... CONCLUSION: Data on these observations should be combined in order to analyse the question of the safety of low-dose methotrexate in these patients.
8350329 Low dose leucovorin does not interfere with the efficacy of methotrexate in rheumatoid art 1993 Jun OBJECTIVE: To determine if simultaneously administered low dose leucovorin interferes with the efficacy of methotrexate (MTX). METHODS: An 8-week double blind placebo controlled study of leucovorin (1 mg) in 16 patients with rheumatoid arthritis receiving chronic MTX was performed at a single academic center. RESULTS: A flare of disease activity was not observed. Clinical variables of arthritis activity did not change in the leucovorin treated population. CONCLUSIONS: Low dose leucovorin when taken simultaneously with MTX did not interfere with the efficacy of MTX in a short term 8 week trial.
1616356 Localisation of fibronectin mRNA in the rheumatoid synovium by in situ hybridisation. 1992 Jun The distribution of fibronectin, an extracellular matrix glycoprotein which plays a part in fibrosis and tissue repair, has previously been described using immunohistochemical methods. These do not differentiate between locally synthesised and plasma derived fibronectin. In this work the distribution of cells actively synthesising fibronectin was assessed by in situ hybridisation using a radiolabelled antisense RNA probe in synovial biopsy samples from patients with rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, and control subjects without inflammatory disease. Large amounts of fibronectin mRNA were found specifically in synovial lining cells, providing evidence for the local production of fibronectin in the synovium. Levels of fibronectin mRNA were variable between patients. These differences were not related to the diagnosis or to the subintimal inflammatory cell infiltrate; where there was synovial lining cell hyperplasia there was a concomitant increase in the number of cells containing fibronectin mRNA, which was consistent with increased levels of immunoreactive fibronectin at this site. Increased levels of fibronectin in synovial fluid in patients with rheumatoid arthritis may be due to an increased number of lining cells secreting the protein, rather than upregulation of the gene by these cells.
7963584 Tolerance to a self-peptide from the third hypervariable region of HLA DRB1*0401 in rheuma 1994 Dec 1 The third hypervariable region (HV3) of HLA-DRB1*0401 helps the development of severe rheumatoid arthritis by an unknown mechanism. To test whether the third hypervariable region of HLA-DRB1*0401 may shape the T cell repertoire, we studied proliferative responses to peptides encompassing the third hypervariable region of seven HLA-DRB1 alleles in normal subjects and patients with rheumatoid arthritis. We found that, in general, there is no tolerance to peptides from the third hypervariable region of self-HLA-DRB1 alleles. However, a peptide from the third hypervariable region of DRB1*0401 (DRB1*0401 HV3 peptide) is tolerated in people who express HLA-DRB1*0401. Indeed, PBMCs from people who express DRB1*0401 do not proliferate to DRB1*0401 HV3 peptide. Conversely, people who express DRB1*1501 respond to DRB1*0401 HV3 peptide. Finally, people who express both DRB1*0401 (nonresponder haplotype) and DRB1*1501 (high responder haplotype) do not respond to DRB1 HV3 peptide, thus demonstrating tolerance. Therefore, the third hypervariable region of HLA-DRB1*0401 shapes the T cell repertoire.
7631988 [Lichenoid eruption induced by gold salts. An autonomous eruption]. 1994 INTRODUCTION: We report a severe lichenoid drug eruption due to gold salts which relapsed 8 months after the cessation of chrysotherapy. CASE REPORT: A 56 year old man, 3 months after the beginning of a gold sodium propanol sulfonate therapy, developed a polymorphous eruption with violin papules on the trunk, eczematous lesions on the limbs and erosive stomatitis. Gold salts were definitively withdrawn. We saw the patient four months after gold therapy cessation: the eruption remained and diagnosis of severe drug cutaneo-mucous lichenoid eruption was done. We saw thereafter the patient again, 8 months after gold therapy cessation: the eruption had relapsed, more intense. DISCUSSION: We suggest that lichenoid eruption, first caused by gold salts, has become autonomous.
8778165 Modifications of biochemical markers of bone and collagen turnover during corticosteroid t 1996 Feb Serum bone Gla protein (BGP), carboxyterminal cross-linked telopeptide of type I collagen (ICTP) and aminoterminal propeptide of type III procollagen (PIIINP) levels were determined in 8 patients with autoimmune disorders (2 with systemic lupus erythematosus, 3 with rheumatoid arthritis, 2 with Sjögren's syndrome and 1 with mixed connective tissue disease) before and after 1, 2 and 4 months of treatment with oral prednisone (at a dosage of 1 mg/kg bw/day, p.o. during the first month, then reduced to 0.1-0.2 mg/kg bw/day). Before treatment mean serum BGP (mean +/- SE: 5.3 +/- 0.4 ng/ml) and ICTP (2.8 +/- 0.2 ng/ml) levels were similar to those recorded in an age and sex matched control group (n = 40: 5.4 +/- 0.1 ng/ml and 4.1 +/- 0.3 ng/ml, respectively). On the other hand, serum PIIINP levels (2.2 +/- 0.3 ng/ml) were significantly (p < 0.008) lower than those found in controls (3.3 +/- 0.2 ng/ml). During glucocorticoid therapy, serum BGP levels significantly decreased after 1 month (2.9 +/- 0.4 ng/ml; P < 0.001), but returned to baseline values after 2 and 4 months of treatment (4.7 +/- 0.4 ng/ml and 5.3 +/- 0.3 ng/ml, respectively). On the contrary, no significant changes were observed in serum ICTP levels during treatment (1st month: 2.7 +/- 0.4 ng/ml; 2nd month: 3.0 +/- 0.4 ng/ml; 4th month: 2.4 +/- 0.3 ng/ml). Serum PIIINP mean concentration significantly decreased after 1 (1.6 +/- 0.3 ng/ml; P < 0.004) and 2 months of glucocorticoid administration (1.5 +/- 0.2 ng/ml; P < 0.01); after 4 months, serum PIIINP levels were again reduced as before therapy (1.8 +/- 0.2 ng/ml). In conclusion, our study shows the presence of normal bone turnover indexes and of altered collagen synthesis in patients with autoimmune disorders. The use of high doses of oral steroids is associated with a prompt decrease of bone formation and collagen synthesis, without any significant changes in bone resorption; however, the negative effects on bone formation and collagen synthesis seem to revert after lowering corticosteroid dosage. Serial determinations of the markers of bone and collagen turnover are able to give useful and reliable information on the peripheral effects of steroids excess.