Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 7955611 | Modulation of the immune response by the neuro-endocrine axis in rheumatoid arthritis. | 1994 Jul | The neuropeptides are involved in the immune response and in hormonal homeostasis. In this review, we analyse the interactions between the cytokine, the neuropeptide and the hormonal networks in rheumatoid arthritis (RA). We first consider pituitary-adrenal axis dysfunction in RA. An inappropriate response to cortisol in chronic inflammation has been reported, i.e., a decrease of the corticotropin-releasing-hormone (CRH) secretion by the hypothalamus. In contrast, the immunostimulant hormone prolactin (PRL) is upregulated. PRL is released by the pituitary after stimulation by neuropeptides [serotonin, thyroid-releasing-hormone (TRH), or vasoactive-intestinal-peptide (VIP)], and is down-regulated by pro-inflammatory cytokines (IL-1, IL-6). The decreased testosterone concentration observed in male RA patients is associated with HLA B 15. Thus, an altered sex hormone status and a genetic predisposition are related to HLA antigens, and increase the subject's susceptibility to the development of RA. The terminal C fibres release neurotransmitters such as substance P, neurokinin A and calcitonin-gene-related-peptide (CGRP) within the joints, and contribute to local inflammation, synoviocyte proliferation and collagenase production. The parasympathetic system may attenuate the immune response through the neuropeptide VIP. In contrast, the beta 2 adrenergic fibres of the sympathetic nervous system increase joints degradation in RA. This review presents the currently extensive knowledge regarding the immune-neuro-hormonal network, and its implication in the pathogenesis of RA. | |
| 8500517 | Abnormalities in left ventricular diastolic function in male patients with rheumatoid arth | 1993 Apr | Epidemiological studies have suggested that patients with rheumatoid arthritis (RA) have increased mortality due to cardiovascular disease. We studied cardiac performance in 12 asymptomatic male patients with RA and 14 control subjects to elucidate early disturbances in cardiac function. In echocardiography, isovolumic relaxation time was longer (64 +/- 6 vs. 49 +/- 3 ms, mean +/- SEM, P = 0.010) and peak filling rate (134 +/- 10 vs. 159 +/- 6 mm s-1, P = 0.015) lower in patients with RA than in control subjects, reflecting an impairment in left ventricular diastolic function. Left ventricular systolic function assessed by radionuclide angiocardiography at rest and during exercise was similar in both groups. There were no differences between the patients with RA and control subjects in the heart rate, systolic blood pressure and oxygen uptake during peak exercise. Left ventricular diastolic function is impaired in spite of normal left ventricular systolic function in patients with RA without clinically evident cardiovascular disease and this may contribute to the excess of cardiovascular mortality in patients with RA. | |
| 1617334 | Receptor-targeted immunotherapy. | 1992 | Modern techniques of genetic engineering have led to the development of novel receptor-targeted immunotherapies for human diseases. These new approaches include mAbs to the CD4+ subset of T cells, immunotoxins for CD5+ T cells, a diphtheria toxin coupled to IL-2, and antibodies to specific TCRs. Additional approaches include a specific IL-1 receptor antagonist and soluble receptors for IL-1 or TNF. Although initially promising, these new approaches to altering immune and inflammatory events need to be thoroughly and carefully evaluated in further clinical trials in human diseases. Perhaps these novel forms of receptor-targeted immunotherapy will eventually prove to be most effective when employed in combination with more conventional anti-inflammatory and immunosuppressive medications. | |
| 7674228 | The relationship of preexisting lung disease to the development of methotrexate pneumoniti | 1995 Jun | OBJECTIVE: To test the hypothesis that preexisting lung disease is a risk factor for the development of methotrexate (MTX) pneumonitis in patients with rheumatoid arthritis (RA) treated with low dose MTX. METHODS: We measured the proportion of patients with and without preexisting lung disease who developed MTX pneumonitis in a historical cohort from a university affiliated rheumatology private practice in Chicago. Patients comprised 93 women and 32 men with RA treated with MTX for any period of time between January, 1980 and July, 1989. RESULTS: MTX pneumonitis occurred in 4 of 77 patients without preexisting lung disease (5.2%) and 5 of 29 (17.2%) patients with preexisting lung disease (p = 0.0610, Fisher's exact test). Five of 24 (20.1%) patients with preexisting lung disease characterized by the report of an abnormal chest radiograph developed MTX pneumonitis (p = 0.2328, Fisher's exact test) and 4 of 16 (25%) patients with interstitial infiltrates reported on their chest radiograph developed MTX pneumonitis (p = 0.0276, Fisher's exact test). CONCLUSION: The presence of preexisting lung disease characterized by radiographic interstitial infiltrates predisposes patients with RA to develop MTX pneumonitis. | |
| 8422556 | Thyroid disease and other autoimmune phenomena in a family study of primary Sjögren's syn | 1993 Jan | Autoimmune diseases and autoantibodies have been documented in 42 index cases with definite primary Sjögren's syndrome (1 degree SS), 207 relatives and 39 spouses. The results were compared with control data from a local population survey. Thyroid disease, 1 degree SS and their associated autoantibodies were the commonest autoimmune abnormalities observed and found predominantly in older female relatives. The HLA-DR3 phenotype associated with 1 degree SS, antinuclear factor, hypothyroidism, and thyroid microsomal antibody. Rheumatoid arthritis and systemic lupus erythematosus were not found in excess in the families. Primary Sjögren's syndrome is frequently associated with thyroid disease and we suggest that there is a common genetic predisposition between these diseases which differs from 2 degrees SS associated with rheumatoid arthritis and systemic lupus erythematosus. This includes MHC and non-MHC genes. | |
| 8835551 | Death attributed to antirheumatic medication in a nationwide series of 1666 patients with | 1995 Dec | OBJECTIVE: Most drugs used in rheumatoid arthritis (RA) can have fatal side effects, but there are no good data on the frequency of such complications. Our study was designed to obtain information on deaths attributable to different antirheumatic drugs. METHODS: The role of antirheumatic medication as a cause of death was studied in 1666 subjects who died in Finland in 1989 and had been entitled under the nationwide sickness insurance scheme to receive specially reimbursed medication for RA. RESULTS: Forty-seven deaths were attributed to antirheumatic medication. Thirty deaths were attributed to the use of nonsteroidal antiinflammatory drugs (NSAID) (17 from peptic ulcer, 11 perforation or hemorrhage of the lower intestinal tract, one renal failure, and one bone marrow depression) and 11 deaths to the use of glucocorticoids (2 from perforations of the lower intestinal tract, 5 osteoporotic fractures, 3 septicemias after intraarticular injections and one adrenal insufficiency after abrupt discontinuation of treatment). There were 2 cases of fatal bone marrow depression attributed to methotrexate and 2 to sulfasalazine, one case of lymphoma induced by azathioprine and one hydroxychloroquine intoxication. In spite of widespread use of injectable gold in Finland, there were no deaths attributed to side effects of gold. CONCLUSION: The data emphasize the frequent occurrence of fatal side effects from NSAID and from glucocorticoids and the relative safety of treatment with gold. | |
| 8448610 | Extra-articular manifestations are uncommon in southern Chinese with rheumatoid arthritis. | 1993 Mar | Rheumatoid arthritis is characterized by both articular and extra-articular manifestations. Few studies have addressed the prevalence of extra-articular manifestations in non-Caucasoid races. We have studied 153 Southern Chinese patients with RA and found that such features are uncommon when compared with previous reports in Caucasoids. The only extra-articular manifestations were rheumatoid nodules which were present in 4.6%, and episcleritis and cutaneous vasculitis in 0.7% each. A further 12.4% had mild sicca symptoms. These findings were in direct contrast with the severity of articular disease as 73% of patients had erosive disease which was graded as severe in 37%. The reason for the low prevalence of extra-articular manifestations is not known but may be due, in part, to the rarity of the HLA-DR4 subtype, HLA-Dw4 in the Southern Chinese population. | |
| 8308422 | Metacarpophalangeal joint arthroplasty based on the osseointegration concept. | 1993 Dec | The osseointegration concept has been used for fixation of 68 MP joint endoprostheses in 31 patients operated on at the Department of Hand Surgery, Malmö General Hospital during the period 1988-1992. The indications were rheumatoid arthritis (50 joints), primary osteoarthrosis (three joints), post-traumatic osteoarthrosis (three joints), post-traumatic osteoarthrosis (five joints), post-infectious osteoarthrosis (seven joints) and joint deformities secondary to spastic conditions (three joints). The average follow-up time was 2.5 years (6-54 months). The surgical procedure included resection of the joint followed by introduction of screw-shaped titanium fixtures into the bone marrow cavities of the metacarpal and the phalangeal base. Rheumatoid cases usually required grafting of cancellous bone and marrow from the iliac crest. At the same time a flexible constrained silicone spacer was connected to the titanium fixtures in such a way as to allow later replacement of the spacer if accessory. The average active range of motion (ROM) was 57 degrees in the rheumatoid cases and 50 degrees in all cases. Radiological and clinical osseointegration occurred in every case, and there were no clinical signs of loosening. In four cases (6%) there was a fracture of the joint mechanism. Patient satisfaction was high, with pain relief, increased range of motion, improved hand function and good cosmetic appearance. | |
| 8060765 | Hypothesis for retroviral causation of rheumatoid arthritis. | 1994 May | Over the past year, convincing direct evidence that rheumatoid arthritis is caused by a retrovirus has not been presented. Strong support for this hypothesis, however, comes from an impressive body of recent work demonstrating that human T-cell lymphotropic virus type I causes a destructive arthropathy that has many of the same features as rheumatoid arthritis. Additional strong support for the hypothesis is provided by the resemblance of the arthropathies induced by caprine arthritis encephalitis and the ovine maedi-visna viruses to rheumatoid arthritis. These retroviral infections emphasize the potential complexity of detecting retroviral involvement and proving its importance in the causation of rheumatoid arthritis. Retroviruses clearly possess diverse pathways for involvement in autoimmune diseases. | |
| 7748223 | EDA-containing fibronectin is synthesized from rheumatoid synovial fibroblast-like cells. | 1995 May | OBJECTIVE: To identify the cells that synthesize EDA-containing fibronectin (FN) and examine the role of EDA+FN in the pathogenesis of rheumatoid joint lesions. METHODS: Localization of EDA+FN and c-Fos protein in rheumatoid joints was studied immunohistochemically by utilizing antibodies for EDA+FN and c-Fos. Expression of EDA+FN was studied by immunoelectron microscopy and in situ hybridization. The amount of EDA+FN was measured by enzyme-linked immunosorbent assay. RESULTS: EDA+FN was specifically localized in the synovial lining layer of synovium with active rheumatoid arthritis (RA) (n = 17), but not in that with osteoarthritis (n = 4) or with inactive fibrous RA (n = 2). EDA+FN messenger RNA was localized in the synovial lining layer. EDA+FN was immunoelectron microscopically localized in the synovial lining fibroblast-like (type B) cells. EDA+FN was also detected at the cartilage-pannus junction and on the surface of RA cartilage. Double staining showed that EDA+FN colocalized with c-Fos protein in the rheumatoid synovial lining layer. Quantification of EDA+FN showed that it was highly concentrated in rheumatoid synovial fluids. CONCLUSION: EDA+FN is synthesized by the synovial lining fibroblast-like (type B) cells in situ in rheumatoid synovium, and appears to be expressed in association with activated or transformed states of synovium. | |
| 8346978 | Small intestinal bacterial overgrowth in patients with rheumatoid arthritis. | 1993 Jul | OBJECTIVES: To examine the microflora of the upper small intestine in patients with seropositive rheumatoid arthritis (RA) using a combination of microbial cultivation and tests for microbial metabolic activity. METHODS: Twenty five patients with seropositive RA, 12 achlorhydric control subjects, and 11 control subjects with normal gastric acid secretion were investigated. Disease activity was evaluated in the patients with RA by three different indices. Eight (32%) of the patients with RA had hypochlorhydria or achlorhydria. The acid secretory capacity was determined with pentagastrin stimulation. A modified Crosby capsule was used to obtain biopsy specimens and samples of intestinal fluid from the proximal jejunum; aerobic and anaerobic microbial cultivation of mucosal specimens/intestinal fluid was carried out, and gas production and microflora associated characteristics in jejunal fluid were determined. Additionally, a bile acid deconjugation breath test was performed. RESULTS: Subjects with at least one of the following findings were considered to have bacterial overgrowth: positive bile acid deconjugation test; growth of Enterobacteriaceae; positive gas production; or low tryptic activity. By these criteria half of the patients with RA with hypochlorhydria or achlorhydria and half of the achlorhydric controls had bacterial overgrowth. Thirty five per cent of the patients with RA with normal gastric acid secretion had bacterial overgrowth compared with none of the normal controls. Disease activity indices and rheumatoid factor titres were significantly higher in patients with RA with bacterial overgrowth than in those without. CONCLUSIONS: A high frequency of small intestinal bacterial overgrowth was found in patients with RA; it was associated with a high disease activity and observed in patients with hypochlorhydria or achlorhydria and in those with normal acid secretion. | |
| 1505103 | Synovitis equivalent to erosions in rheumatoid arthritis: implications of skeletal analysi | 1992 Mar | Examination of a contemporary skeletal collection revealed a rheumatoid subgroup with parameters mirroring those of contemporary clinical populations. This rheumatoid population was also indistinguishable from contemporary (live) clinical populations, on the basis of the actual distribution of radiologically detectable erosions, thus validating its representativeness. Gross examination of these defleshed skeletons allowed assessment of the significance of erosive disease in rheumatoid arthritis. As anticipated, the frequency of visibly detectable erosions exceeded that detectable radiologically. The frequency of visibly detectable erosions, however, was indistinguishable from the frequency of synovitis in clinical populations. The excellent correlation of the gross and clinical distribution of disease suggests that some degree of erosive disease is integral to all lesions of rheumatoid arthritis and that only the relative insensitivity of radiologic techniques precludes universal recognition of those erosions. This work suggests that any therapeutic intervention which settles for only partial synovitis control will not prevent the progression of erosive disease; and perhaps explains the difficulty of demonstrating alterations in erosion progression in studies of disease modifying agents. | |
| 8484132 | Hypogammaglobulinemia and rheumatic disease. | 1993 Feb | Primary hypogammaglobulinemia describes a heterogeneous group of immunoglobulin disorders mainly composed of X-linked agammaglobulinemia, common variable immunodeficiency, and selective immunoglobulin (Ig) A deficiency. The most serious problems are related to recurrent infections with high-grade encapsulated bacteria. However, a wide variety of rheumatologic disorders also occur in association with hypogammaglobulinemic states. Septic arthritis with usual bacterial pathogens such as Staphylococcus aureus, and unusual bacteria such as Mycoplasma and Ureaplasma species, have been described in these patients. An aseptic nonerosive polyarticular arthritis that resembles rheumatoid arthritis is seen in 10% to 30% of hypogammaglobulinemic patients. Autoimmune disorders such as immune thrombocytopenic purpura, immune hemolytic anemia, juvenile rheumatoid arthritis, systemic lupus erythematosus, dermatomyositis, Sjögren's syndrome, essential mixed cryoglobulinemia, chronic active hepatitis, and sarcoidosis have been reported in hypogammaglobulinemic patients. Finally, to complicate matters, many disease-modifying antirheumatic drugs, including gold, D-penicillamine, sulfasalazine, azathioprine, and cyclophosphamide, cause symptomatic hypogammaglobulinemia in some patients. | |
| 8362408 | Sequence-specific oligonucleotide typing in Shona patients with rheumatoid arthritis and h | 1993 Apr | Seventy-two patients with rheumatoid arthritis (RA) and 82 controls have been typed with the XI Histocompatibility Workshop DRB1 and DQB1 sequence-specific oligonucleotide probes. The increase of DRB1*04 corresponds to an increase of the serologically defined DR4, previously found in a small group of Zimbabwean RA patients and we now show that this increase is due to the subtype DRB1*0405 in association with DQB1*0302. In addition there is a clearcut increase of DRB1*1001 equivalent to the serologically defined DR10. There was no increase amongst RA patients of DRB1*0102 which was the predominant DR1 sub-type amongst controls. In the course of our investigation, we observed a DRB1*04 variant which corresponds to DRB1*0412, newly defined in the XIth Histocompatibility Workshop. | |
| 7495919 | Decreases in health care resource utilization in patients with rheumatoid arthritis follow | 1995 Sep | We previously reported the efficacy of a multicomponent cognitive-behavioral intervention including biofeedback to decrease pain, affective distress, and objective measures of disease activity in patients with rheumatoid arthritis (RA). In the present article we report evidence that this intervention is associated with reductions in RA-related clinic visits and days hospitalized as well as reductions in the costs of these medical services. Data were independently and objectively collected over an 18-month interval as part of a controlled group outcome study. The importance of documenting economic as well as clinical benefits of our treatments in specific patient populations is noted. | |
| 8448637 | The effects of cyclosporin A on bone and cartilage. | 1993 Mar | Cyclosporin A (CyA) is a potent immunomodulatory agent with an increasing number of clinical applications. Although its precise mechanisms of action are yet to be elucidated, one of the most important known properties of CyA is its ability to inhibit the production of cytokines involved in the regulation of T cell activation. There is also evidence for direct effects on other cell types, such as B cells, macrophages, and bone and cartilage cells. The effects of CyA on T cells and on bone, cartilage and synovial cells, which can produce a range of cytokines, are of interest in the study of inflammatory diseases such as RA. It has been shown, for example, that in vitro CyA inhibits bone resorption induced by interleukin-1, 1,25-dihydroxy-vitamin D3, parathyroid hormone and prostaglandin E2. In vivo, it protects against adjuvant arthritis. | |
| 8060767 | Intravenous immunoglobulin therapy for rheumatic diseases. | 1994 May | Although clearly demonstrated in idiopathic thrombocytopenic purpura and Kawasaki disease, the efficacy of intravenous immunoglobulins in the treatment of rheumatic and connective tissue diseases remains to be confirmed in double-blind placebo-controlled studies. This article is a review of some rheumatic and connective tissue diseases (ie, rheumatoid arthritis, juvenile rheumatoid arthritis, Still's disease, systemic lupus erythematosus, dermatomyositis-polymyositis, and vasculitis) in which anecdotal open studies occasionally have shown impressive clinical and biologic results with good tolerance. Intravenous immunoglobulins contain idiotypic antibodies directed against pathologic autoantibodies and appear to be an interesting source of immunomodulating antibodies, which could be useful in the treatment of autoimmune diseases. | |
| 8246585 | Effect of acupuncture and point-injection treatment on immunologic function in rheumatoid | 1993 Sep | The results of treatment of 54 cases of rheumatoid arthritis (RA) by warm needling (WN) and point-injection (PI) with Zhuifengsu are reported. Good clinical results were observed with an effective rate of 100%. At the same time, changes in cellular and humoral immunity and other parameters in peripheral blood were noted before and after treatment. The NK activity and IL-2 value in RA patients were found to be lower than those of normal individuals; both increased after treatment (P < 0.01). This suggests that the WN and PI with Zhuifengsu exert a regulatory effect on the cellular immunological function. | |
| 8516619 | Intrasynovial levels of sulphated glycosaminoglycans and autoantibodies to type II collage | 1993 | It is uncertain whether the autoantibodies to type II collagen that occur frequently in the serum and synovial fluid of patients with rheumatoid arthritis (RA), but rarely in other articular diseases, are primary or secondary to cartilage damage. Hence, we measured antibodies in synovial fluid from patients with RA and other articular diseases and related these to the concentration of sulphated glycosaminoglycans, as a measure of ongoing cartilage catabolism. Synovial fluids from 42 patients with RA and 30 patients with other articular diseases were studied. We found that levels of antibodies to native and denatured collagen were significantly higher in RA than in all other articular diseases, whereas concentrations of sulphated glycosaminoglycans were similar. The absence of any correlation between levels of sulphated glycosaminoglycans and antibodies to collagen weighs against the occurrence of such antibodies in RA as a secondary effect of cartilage damage. | |
| 8465131 | [Low-dose steroids in chronic polyarthritis: a basic therapy?]. | 1993 Mar 23 | The symptomatic and disease-modifying efficacy of low-dose corticosteroids in rheumatoid arthritis is explained. A possible therapeutic effect of low-dose corticosteroids is shown by long-term studies which include radiological evaluation. The safety and side-effects of low-dose corticosteroids are described. Steroid-induced osteoporosis in rheumatoid arthritis is discussed especially based on recently accomplished longitudinal bone density studies. Finally consequences in the management of rheumatoid arthritis are defined. |