Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 2840085 | Synovial fluid collagenase in patients with destructive arthritis of the shoulder joint. | 1988 Jul | We studied synovial fluid (SF) collagenase in 10 women with severe rheumatoid arthritis (RA), 10 with pyrophosphate arthropathy, and 10 with idiopathic destructive disease of the shoulder conforming to a pattern recently described. SF cell counts were highest in the RA group. Particles were detected by polarized light microscopy and alizarin red staining. Crystals were seen in fluids from all 3 groups; pyrophosphate predominated in the pyrophosphate arthropathy group and alizarin red-positive particles in the idiopathic disease group. Collagenase and tissue inhibitor of metalloproteinase levels were estimated in SF after gel filtration. Tissue inhibitor of metalloproteinase activity was detected in all fluids, but tended to be highest in the RA group. Collagenase activity was detected in 3 RA fluids only. In no sample was collagenase found in an active form. These findings support the clinical concept of an aggressive destructive process which sometimes occurs in the shoulder joints of elderly women. Because we were not able to detect free collagenase in SF from any of the patients with idiopathic shoulder disease, the data suggest that high levels of active collagenase are not characteristic of this group of patients. | |
| 2306574 | New referrals to rheumatology clinics--why do they keep coming back? | 1990 Feb | Many rheumatologists are concerned at the number of return visits being made to their out-patient clinics. This study investigates the outcome of 179 general practitioner referrals to two rheumatology clinics during 1987. Forty-one (34%) of the rheumatoid arthritis patients and six (10%) of the osteoarthritis patients made four or more visits. Junior staff discharged far fewer (11-18%) of patients than did consultants (34%). Multiple linear and multiple logistic regression analyses were performed for the demographic and clinical variables which seemed (on univariate analyses) to predict continuing attendance. The maximum disease severity, diagnosis of rheumatoid arthritis, male sex, patient's perceived reason for referral and the hospital clinic only explained 21% of the variation in the number of visits made. Most of the factors influencing hospital clinic doctors are not easily apparent. The data suggested only one method of reducing unnecessary out-patient attendances, namely to increase the number of patients seen by a consultant. Differences in 'clinic policies' and individual doctor's decision-making strategies will require further study. | |
| 2509696 | Rheumatoid arthritis with eosinophilic fasciitis and pure red cell aplasia. | 1989 Oct | A case of longstanding rheumatoid arthritis with concurrent development of eosinophilic fasciitis and pure red cell aplasia is described. A simultaneous occurrence of all 3 disorders has not been reported. Treatment with moderate dosages of prednisone resulted in a prompt and complete remission of both the fasciitis and the selective marrow aplasia. | |
| 2572230 | Anti-CD4 antibody treatment of patients with rheumatoid arthritis: I. Effect on clinical c | 1989 Oct | Eight patients with arthritis (seven with rheumatoid, one with psoriatic arthritis) were treated for 7 d with a daily injection of 10 mg of mouse monoclonal anti-CD4 antibodies (three with VIT4, five with MT151). With the exception of a short-lasting low-grade fever in one patient, no side effects were observed. Clinical symptoms (morning stiffness, number of swollen joints, pain assessment and Ritchie articular index) improved in all patients within 7 d of treatment. Improvement lasted from 3 weeks to greater than or equal to 5 months (mean approximately 11 weeks). Rheumatoid factors, immune complexes and other laboratory parameters did not change during or after treatment. Skin reactivity to recall antigens was suppressed in four out of six patients during treatment but returned to pretreatment levels within 6 weeks. Immunofluorescent analysis revealed a short-lasting drop of T cells, mainly of the CD4+ CDw29+ subset, but monocytes were also affected. The injected antibody was detectable on circulating cells for about 10 h. Within 20-24 h, the cell distribution returned to pretreatment levels. In six out of eight patients an anti-mouse-Ig response was seen. We conclude that mouse anti-CD4 monoclonal antibody (MoAb) treatment is well tolerated and that the cellular immunological changes observed are short-lasting. The low incidence of side effects may justify further clinical studies to evaluate the clinical efficacy of such treatment. | |
| 2673080 | Feverfew in rheumatoid arthritis: a double blind, placebo controlled study. | 1989 Jul | Feverfew, reputed by folklore to be effective in arthritis, has in vitro properties that could be beneficial in the control of inflammatory disease. Forty one female patients with symptomatic rheumatoid arthritis received either dried chopped feverfew (70-86 mg) or placebo capsules once daily for six weeks. Allocation was random and not known by patient or observer. Variables assessed included stiffness, pain (visual analogue scale), grip strength, articular index, full blood count, erythrocyte sedimentation rate, urea, creatinine, C reactive protein, complement breakdown products (C3dg), rheumatoid factor titre, immunoglobulins (IgG, IgA, IgM), functional capacity, and patient and observer global opinions. One patient (placebo) withdrew after three days and was not included in the analysis. Treatment and placebo groups (20 patients each) were well matched at entry. No important differences between the clinical or laboratory variables of the groups were observed during the six week period. This study therefore shows no apparent benefit from oral feverfew in rheumatoid arthritis. | |
| 2441453 | [Anti-keratin antibodies. A marker of progressive rheumatoid arthritis]. | 1986 Nov | Anti-keratin antibodies have been detected by indirect immunofluorescence on rats esophageal sections in 122 rheumatoid polyarthritis, 100 seropositive and 22 seronegative. The frequency of anti-keratin antibodies is 58 p. cent in seropositive rheumatoid polyarthritis and 41 p. cent in seronegative rheumatoid polyarthritis. Anti-keratin antibodies have a very good specificity (96 p. cent) for rheumatoid polyarthritis since in a group of 105 controls, only 4 sera were found to have a low titre of anti-keratin antibodies (1 ankylosing spondyloarthritis, 2 sclerodermis, 1 healthy subject). The mean titre of antikeratin antibodies is higher in seropositive rheumatoid polyarthritis than in seronegative rheumatoid polyarthritis. Within seropositive rheumatoid polyarthritis, the titre of anti-keratin antibodies is correlated with the titre of rheumatoid factors determined by the latex test (r' = 0.464, p less than 0.01). The presence of anti-keratin antibodies is correlated with the degree of functional handicap evaluated by the functional index of Steinbrocker (p less than 0.02) and with the biological evolution evaluated by the sedimentation rate (p less than 0.001). No correlation was found with accidents of intolerance to fundamental treatments (gold salts, D-penicillamine), especially skin diseases. Anti-keratin antibodies represent therefore a diagnostic marker for seropositive rheumatoid polyarthritis as well as seronegative ones and an evolutive marker of seropositive rheumatoid polyarthritis. | |
| 2059231 | Subclass distribution and size of human IgA rheumatoid factor at mucosal and nonmucosal si | 1991 Jul | Elevated serum levels of IgA, IgA1, and IgA2 rheumatoid factors (RF) were demonstrated by enzyme-linked immunosorbent assay in 69%, 73%, and 36%, respectively, of 100 patients with rheumatoid arthritis (RA), whereas fewer than 5% of 100 healthy donor sera contained elevated levels of these RFs. In serum samples from 125 controls with 4 different chronic diseases (systemic lupus erythematosus, ankylosing spondylitis, bronchial asthma, and polyarteritis nodosa), levels of IgA-, IgA1-, and IgA2-RF were found to be increased in 7%, 7%, and 8%, respectively. Comparison of RF levels in samples of serum, synovial fluid (SF), and saliva from RA patients indicated local production of both IgA-RF subclasses in salivary glands and in synovial tissue. Significant positive correlations were found between levels of IgA-RF subclasses in SF and serum, but not in serum and saliva or in SF and saliva. Fractionation of serum, SF, and saliva from patients with RA (by high performance liquid chromatography under acidic conditions) demonstrated that both IgA subclasses with RF activity occur mainly in fractions that also contain IgM. The results of this study show that 1) IgA-RF in serum and SF is mainly of IgA1 subclass, 2) both IgA-RF subclasses are produced locally in salivary glands and in synovial tissue, 3) the production of both IgA-RF subclasses at mucosal and nonmucosal sites is independent from each other, and 4) both IgA-RF subclasses occur predominantly in polymeric form in serum, SF, and saliva in RA patients. | |
| 3399796 | Down-regulation of immunoglobulin and IgM-rheumatoid factor synthesis by oral treatment of | 1988 | We examined the effect of treatment with piroxicam, a nonsteroidal antiinflammatory drug (NSAID), on immunoglobulin (Ig) and IgM-rheumatoid factor (IgM-RF) synthesis in vitro by lymphocytes of patients with rheumatoid arthritis (RA). Oral treatment with piroxicam induced a progressive decrease of spontaneous IgM-RF production by unstimulated lymphocyte cultures during 12 weeks of observation. Also, pokeweed mitogen (PWM)-driven Ig synthesis was significantly diminished and the effect on total IgM production was sustained until the end of the study. This modulation of humoral responses is consistent with the drop in RF sera level. In addition, we also showed that treatment with NSAIDs can decrease RF levels in the synovial space. NSAIDs may have a long-term beneficial effect in patients with RA due to their modulatory role of lymphocyte responses. | |
| 2098385 | Radiographic changes in the temporomandibular joint of patients with rheumatoid arthritis, | 1990 Winter | Sixty-one subjects with rheumatoid arthritis, 61 with psoriatic arthritis, 61 with ankylosing spondylitis, and 77 healthy controls were examined using orthopantomography to determine the frequency of radiographic changes in the condyle of the temporomandibular joint. Radiographic changes were found significantly more often in subjects with rheumatoid arthritis (66%), psoriatic arthritis (38%), and ankylosing spondylitis (30%) than in controls (12%). Subjects with rheumatoid arthritis also had significantly more radiographic changes, especially cortical erosions and subcortical cysts, than subjects with psoriatic arthritis or ankylosing spondylitis. It may be concluded that rheumatoid arthritis is a more severe disease than psoriatic arthritis or ankylosing arthritis regarding temporomandibular joint involvement. | |
| 3797956 | An inhibitor of complement-mediated prevention of immune precipitation in rheumatoid arthr | 1986 | In normal serum complement prevents precipitation of antigen-antibody complexes (PIP). However rheumatoid arthritis (RA) serum contains an inhibitor of this complement-mediated function. We have undertaken two prospective studies in order to look for any relationship between the presence and levels of inhibitory activity in sera and synovial fluids (SF) of patients with RA and disease activity (study A), and the presence of systemic manifestations (nodules and vasculitis) of RA (study B). In study A, levels of inhibitory activity were highest in the sera and synovial fluids of patients with seropositive RA. However there was no correlation between the inhibitory levels and indices of generalised disease activity (articular index, erythrocyte sedimentation rate (ESR), haemoglobin, white cell and platelet counts). Local joint tenderness score correlated weakly with the inhibitory level in SF (P less than 0.05). There was no correlation, however, with either the SF protein concentration or white cell count. In study B, PIP was shown to be lower in patients with the systemic manifestations of RA than in those with purely articular manifestations. PIP was particularly low in those patients with vasculitis compared to those with subcutaneous nodules. Serum levels of inhibitory activity were highest in patients with vasculitis and lowest in those with articular disease only, whereas patients with nodules had intermediate levels. Our conclusion is that inhibition of immune precipitation is not associated with disease activity, but is associated with the extra-articular manifestations of RA. The inhibitory factor may play a role in the pathogenesis of RA. | |
| 3486811 | [Pathogenesis and therapy of rheumatoid inflammation]. | 1986 May | By initial 3H-thymidine labelling an enhanced monocyte proliferation in the bone marrow of patients with rheumatoid arthritis is demonstrated. The significant monocyte proliferation correlates positively with the erythrocyte sedimentation rate but shows a negative correlation with age. The high significance of the mononuclear phagocyte (MNP) system in the pathogenesis of rheumatoid arthritis is seriously underlined by the experimental findings in our allergic arthritis model. Benoxaprofen as an inhibitor of the lipoxygenase pathway and of the inflammatory monocyte influx significantly suppresses the experimental allergic synovitis. These findings stress upon the important role of the MNP-system in the pathogenesis of rheumatoid arthritis and demonstrate the significance of the monocytes/macrophages as an important target-cell system for antirheumatic drugs. | |
| 3558732 | The molecular basis for HLA class II associations with rheumatoid arthritis. | 1987 Jan | The association of HLA-DR4 with rheumatoid arthritis strongly implicates genes of the major histocompatibility complex (MHC) as contributing to disease susceptibility. Molecular analysis of MHC genes expressed on haplotypes in association with HLA-DR4 reveals that at least six different alleles of the DR beta 1 locus and at least three different alleles of the DQ beta locus occur on different DR4+ haplotypes. Some of these allelic differences are quite substantial, and others are rather subtle, involving as few as two amino acids. The analysis of individual DR and DQ alleles in rheumatoid arthritis identifies some DR4+ genes strongly associated with disease susceptibility and some DR4+ genes which are not. The Dw4(DR4) and Dw14(DR4) DR beta 1 genes appear to represent specific alleles which confer disease risk in RA; other DR beta 1 genes, such as Dw10(DR4), may represent DR beta genes altered during evolution which have lost their contribution to RA susceptibility. DQ beta 3.1(DQw3) and DQ beta 3.2(DQw3) DQ beta genes, which are present on DR4+ haplotypes, represent discrete variable alleles not directly implicated in RA, but which account for HLA-DR4 associations with other diseases, such as the association of DQ beta 3.2(DQw3) with Type I diabetes. | |
| 3355257 | Value of joint scintigraphy in the prediction of erosiveness in early rheumatoid arthritis | 1988 Mar | The value of scintigraphy in predicting development of new erosions in small peripheral joints was studied by visual evaluation of scintigrams and by three computerised methods. In 13 patients with newly diagnosed rheumatoid arthritis a total of 387 joints were examined clinically, scintigraphically, and radiographically. The follow up period was 24 months. Four eroded joints in three patients were found at the onset. Of the joints which were to become eroded, 46/47 were scintigraphically active at all the check ups. Erosions were detected earlier in foot joints than in finger joints. New erosions were especially prone to appear in joints with persisting and high scintigraphic activity. On the contrary, inactive joints by repeated scanning never eroded. Scintigraphic and clinical activity and radiographic erosiveness correlated significantly with each other. The sensitivity and specificity of visual scintigraphic assessment and the relative pixel activity method proved to be superior to the region of interest methods and clinical evaluation for prediction of erosiveness. | |
| 2763768 | Resection arthroplasty of the rheumatoid forefoot. | 1989 | After discussing the term of resection arthroplasty of the rheumatoid forefoot, the problem of indications and contraindications for surgery is dealt with. Experience obtained by operations is presented together with the recommended operative technique. | |
| 2746585 | The immunohistologic features of synovitis, disease activity and in vitro IgM rheumatoid f | 1989 Apr | The immunohistologic characteristics of synovial membrane obtained from patients with active rheumatoid arthritis (RA) were correlated with disease activity and spontaneous in vitro synthesis of IgM rheumatoid factor (RF) by peripheral blood mononuclear cells (MNC). Positive correlations were found between the intensity of inflammatory cell infiltration and both disease activity (p = 0.0007) and RF synthesis (p = 0.028). Moreover, the intensity of both T cell and B cell infiltration correlated significantly with disease activity. Within the group studied 3 previously described immunohistologic categories were identified. These categories could not be distinguished by clinical measurements, but did differ with respect to their capacity for spontaneous in vitro IgM RF synthesis by blood MNC. Our study provides evidence that a relationship does exist between the immunohistologic characteristics and disease severity in RA. Furthermore, the concept of distinct histologic categories of RA representing different immunopathogenic mechanisms is supported. | |
| 3208454 | Measurement of terminal complement complexes in rheumatoid arthritis. | 1988 Sep | Though complement activation is recognized as a central event in inflammation in the rheumatoid joint, little attention has been paid to the role of the cytolytic membrane attack complex of complement in the pathogenesis of this disease. The membrane attack complex causes a variety of non-lethal effects in nucleated cells, including stimulation of release of inflammatory mediators, and cell proliferation. Thus in the rheumatoid synovium, non-lethal effects of complement membrane attack may play a major role in disease pathology. In order to investigate this possibility, assays for the detection of terminal complement complexes in biological fluids have been established, and used to demonstrate membrane attack pathway activation in rheumatoid arthritis. Terminal complement complexes were present in increased levels in synovial fluid (mean, 1,334 ng/ml) and plasma (mean, 513 ng/ml) in 20 patients with rheumatoid arthritis when compared with controls (mean, 285 ng/ml and 129 ng/ml respectively). Using an assay specific for the SC5b-9 complex it was demonstrated that the raised levels of terminal complement complexes in rheumatoid synovial fluid consisted of a mixture of inactive SC5b-9 complexes and fluid-phase complement membrane attack complexes. | |
| 1700052 | Human HLA-DR beta gene hypervariable region homology in the biobreeding BB rat: selection | 1990 Nov 1 | Collagen arthritis (CA), an autoimmune model of rheumatoid arthritis (RA), has been studied in various animals. However, it has not been studied in an animal with a genetic background relevant to RA. We selected rats from a diabetic-resistant (DR) subline of the diabetic BB rat because they have an autoimmune disease-prone background, but not the immunodeficiencies of the diabetic BB rat, and the third hypervariable region (HVRIII) of the BB RT1.D beta gene appeared to encode a nucleotide sequence of the human HLA DR beta gene, which has been reported to be associated with susceptibility to RA. We synthesized oligonucleotide primers flanking the RT1.D beta HVRIII, cloned polymerase chain reaction-amplified DNA into M13mp18, and confirmed the presence of the susceptibility sequence (SS) (RRRAA) by the dideoxy sequencing method in a colony of DR BB/Wor-UTM rats. When immunized with human type II collagen (CII) in incomplete Freunds adjuvant (IFA), arthritis developed rapidly by day 10 with 100% incidence. Light and electron microscopy revealed an unusually severe and aggressive, bidirectional pattern of cartilage resorption by synovial and subchondral mononuclear and multinucleated inflammatory cells. These findings coincided with a predominant humoral response to the cyanogen bromide (CB) 11 fragment of the human CII molecule by the pathogenic IgG2a isotype. This study provides further support to the role of CA as a relevant RA model, the specific roles of the CB11 fragment as a major site of arthritogenic epitopes, and of antibody mechanisms in the pathogenesis of CA. Furthermore, the identification of an RA SS in an immune response gene of the DR BB rat presents a novel opportunity to determine with an animal model the role of other antigens as well as this SS in RA. | |
| 3397979 | Influence of age and disease state in nonsteroidal antiinflammatory drug associated gastri | 1988 Apr | In our study of 552 acute admissions for gastrointestinal hemorrhage, 18% were found to be taking nonsteroidal antiinflammatory drugs (NSAID) at the time of the bleed; 49% of these were found at endoscopy to have a gastric or prepyloric lesion, compared with 20% of the non-NSAID control group. Prescription data was used to calculate the risk added by age and disease state to the NSAID associated bleeding. We found that patients with chronic inflammatory disease had 2-3 times the expected bleeding incidence, but while there was a definite trend towards an age related risk in older patients, this was not statistically significant. | |
| 2042009 | [Thiol-proteolytic activity in rheumatoid polyarthritis. Assay by spectrofluorimetry]. | 1991 Feb | Joint and bone damage in rheumatoid arthritis is thought to be caused primarily by an imbalance between proteolytic proteinases and their specific inhibitors. Matrix destruction can in part result from the activity of lysosomal cystein proteinases such as cathepsin B and L. Cathepsins usually are determined by enzyme immuno-assay. The aim of this study was the direct determination of synovial thiol-proteolytic activity by spectrofluorimetry using a synthetic substrate (Z-Phe-Arg-NMec) and a cystein proteinase specific inhibitor (E64 = L-trans-epoxy-succinyl-leucylamino-(4 guanidino)-butane). 18 rheumatoid synovial fluids were tested compared to 10 osteoarthritic synovial fluids. Thiol-proteolytic activity appeared higher in rheumatoid arthritis compared to osteo-arthrosis (mean value = 1,311 mU/l vs 156 mU/l, p less than 0.01). Synovial thiol-proteolytic activity is well correlated with synovial elastase-alpha1-proteinase-inhibitor complex. The authors found no correlation with synovial polymorphonuclear count (p = 0.38) nor with clinical and biological parameters of disease evolution. The highest values were observed in patient with radiological signs of joint destruction. Synovial thiol-proteolytic activity might represent the potential destructive evolution of rheumatoid arthritis. | |
| 2821854 | Lower respiratory tract abnormalities in rheumatoid interstitial lung disease. Potential r | 1987 Oct | Although the etiology of rheumatoid interstitial lung disease (RILD) remains unknown, bronchoalveolar lavage (BAL) has been useful in studying potentially pathogenic mechanisms in this disorder. Previous investigations in patients with rheumatoid arthritis (RA) and RILD revealed abnormal BAL T-lymphocyte subpopulations and a significant elevation in BAL neutrophils. Because neutrophils have been implicated as important effector cells in inflammatory disorders such as ARDS and idiopathic pulmonary fibrosis, we evaluated BAL fluid in patients with RA for neutrophil chemotactic and activating properties and for evidence of neutrophil activation. The BAL fluid from patients with RILD contained significant neutrophil chemotactic activity derived from both lipid and nonlipid components. Evidence for neutrophil stimulation in the lower respiratory tract of patients with RILD was suggested by elevations in both myeloperoxidase activity and immunologically determined levels of human neutrophil elastase in BAL fluid. Free uninhibited elastolytic activity, however, was not demonstrated, suggesting that adequate protease inhibitor levels were present to inhibit active elastase activity. In addition to elevated myeloperoxidase activity, a potential role for neutrophil-derived oxidant injury was indirectly suggested by the enhanced release of superoxide anion (O2-) from resting normal human blood neutrophils challenged with concentrated BAL fluid from patients with RA and interstitial lung disease. Significant correlations were found between physiologic parameters and the percentage of BAL neutrophils, as well as levels of neutrophil-derived mediators. For example, levels of human neutrophil elastase were strongly correlated with diminished diffusion capacity (r = -0.73, p less than 0.001) and reduced forced vital capacity (r = -0.63, p less than 0.006).(ABSTRACT TRUNCATED AT 250 WORDS) |