Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
8620624 Sera of patients with rheumatoid arthritis contain antibodies to recombinant human T-lymph 1996 May A possible retroviral etiology for rheumatoid arthritis (RA) has been raised by results of recent studies. Therefore, we examined sera of patients with RA, including those with coexisting Felty's syndrome or leukemia of large granular lymphocytes, for the presence of antibodies to retroviral proteins of human T-lymphotrophic virus type I and type II (HTLV-I/II). Reactivity to recombinant HTLV-I envelope protein rgp21 alone was the primary pattern observed. Twenty-five percent of RA sera, 28% of Felty's syndrome sera, and 30% of large granular lymphocyte leukemia/RA sera reacted with rgp21, each significantly more than the 8% of normal sera (P less than 0.01). Removing rheumatoid factor did not abolish reactivity with rgp21 in any of six RA sera tested. Immunoreactivity to the authentic viral protein was confirmed by using purified rgp21 that was cleaved by CNBr to remove the bacterial fusion peptide, or by blocking sera with a synthetic peptide corresponding to the fusion peptide. Only one serum, from a patient with RA, showed definite evidence for prior infection with prototypic HTLV-II. These data indicate that 25% of RA sera have IgG antibodies to recombinant HTLV-I envelope protein rgp21, which is highly homologous to envelope protein gp21 of HTLV-II. These findings provide potentially novel clues regarding the pathogenesis of RA.
8542205 In vitro duodenal iron uptake and serum and mucosal iron protein levels, with special refe 1995 Nov Duodenal biopsies from control subjects, patients with iron-deficiency anaemia and rheumatoid arthritic patients with anaemia of chronic disorders (ACD) were investigated for their ability to take up 59Fe from iron ascorbate. Additionally, duodenal tissues were analysed for iron and immunoreactive ferritin and transferrin. Biopsies from iron-deficient subjects showed a 2- to 3-fold increase in the apparent Vmax for 59Fe uptake, compared to control values. Uptake was inversely related to body iron stores. ACD patients showed similar rates of 59Fe uptake to controls; the rates were independent of the degree of anaemia or serum ferritin levels. Tissue analysis showed reductions in mucosal iron and ferritin levels in iron-deficient patients, whilst transferrin levels were within the normal range. ACD patients also exhibited lower mucosal iron levels, but had iron protein levels within the normal range. It is suggested that factors distant from the intestinal mucosa influence iron absorption in ACD.
7775894 Anticardiolipin antibodies in rheumatoid arthritis. 1994 The presence of anticardiolipin antibodies (aCL IgM & IgG), rheumatoid factor (RF) C-reactive protein (CRP) and antinuclear antibodies (ANA) were evaluated in 26 patients with rheumatoid arthritis (RA) disease [12 patients with acute disease (gr 1), 14 patients with chronic disease (gr 2) and 10 normal subjects as control (gr 3)]. aCL IgM was significantly increased in gr 1 & gr 2 when compared with gr 3 (P < 0.001 & P < 0.010 respectively). aCL IgG was non significantly increased in gr 1 & gr 2 when compared with gr 3 (P < 0.076 & P < 0.022 respectively). In group 1 75% of the patients were positive for a CLIgM, 25% positive for a CLIgG, 75% for RF, 58.3% for CRP, 25% positive for ANA Shaggy pattern and 33.3% positive for ANA speckled pattern. In group 2, the percent of positive cases were 42.85% for a CLIgM, 14.28% for a CLIgG, 42.8% for RF, 57.14% for CRP, 14.25% for ANA shaggy pattern and 28.57% for ANA speckled pattern. In the control group, all antibodies proved to be negative in every case. There was positive correlation between a CL IgM & aCLIgG and duration of disease in gr 1 & gr 2. There was positive correlation between a CLIgM and ESR in gr 1. There was negative correlation between a CLIgG and ESR in gr 1. There was negative correlation between a CLILgM & ESR in gr 2. There was positive correlation between a CLIgG & ESR in gr 2. We conclude that the presence of a CL antibodies (IgM & IgG) correlate well with the activity of disease, so this draw our attention to the importance of a CL antibodies as a parameter for prognosis of the disease.
7973476 Effects of strength training on neuromuscular function and disease activity in patients wi 1994 Thirty-nine consecutive patients with recent-onset rheumatoid or psoriatic arthritis were randomly allotted for six months period either to the experimental progressive dynamic strength training group (EG, 10 women and 11 men; 41 +/- 10 yrs), or to the control group (CG, 10 women and 8 men; 45 +/- 11 yrs) who just maintained their habitual physical activities. All patients received antirheumatic medication throughout the experimental period. During the study period significant improvements took place in the EG in maximal muscle strength of all examined muscle groups (31.5% for the knee extensors, p < 0.001; 14.8% and 10.7% for the trunk flexors and extensors, p < 0.01; 27.8% and 20.4% for grip strength, p < 0.001) as well as in erytrocyte sedimentation rate (p < 0.05). Ritchie's articular index (RI) (p < 0.001) and HAQ (p < 0.01). In the CG only the decrease in RI was statistically significant (p < 0.05). Erosive changes in joints increased only slightly and less in the EG than in the CG. The present results suggest that dynamic strength training in early arthritis increases the neuromuscular performance without detrimental effects on disease activity or joint damage.
7540786 [Immunomodulating therapy of rheumatoid arthritis (chronic polyarthritis): use of monoclon 1995 Mar Rheumatoid arthritis is a chronic inflammatory disease mainly affecting the joints. The etiology is still unknown, but it shows several clinical and laboratory features of an autoimmune process. The conventional medical therapy consisting of a combination of analgetic and antiphlogistic agents with so called slow acting drugs is often not satisfactory and fails to persistently suppress disease activity. Therefore, therapeutic alternatives are necessary which are provided by a new generation of immunosuppressing agents including monoclonal antibodies. The paper will summarize some therapeutic approaches using monoclonal antibodies towards cell surface antigens or soluble mediators of inflammation for therapy of rheumatoid arthritis.
7483738 [Therapy refractory atypical polyarthritis and cryoglobulinemia in a patient with colon ca 1995 Aug The case of a 63 year old woman with mesenteric recurrence of a colonic carcinoma and infiltration of the duodenum is reported. To bypass duodenal stenosis a duodenojejunostomy was performed. Three months later the patient developed severe atypical polyarthritis which led to hospitalization. The arthritis affected large and small joints in an asymmetrical pattern. Fever and Raynaud's phenomenon of both hands accompanied the arthritis. Elevated sedimentation rate, acute phase proteins, cryoglobulinemia and immune complexes were remarkable laboratory findings. Rheumatoid factor was absent. In the subsequent course the polyarthritis was refractory to steroids and nonsteroidal anti-inflammatory drugs. Only treatment with broad-spectrum antibiotics ameliorated the arthritis. Postenteric reactive arthritis, septic arthritis and metastatic arthritis could be excluded. Although the patient had a family history of rheumatoid arthritis and a HLA-type DR4 the diagnosis of rheumatoid arthritis was not very likely since distal interphalangeal joints were affected, rheumatoid factor was absent and antibiotic therapy was successful. The case serves to discuss carcinoma-polyarthritis and bypass-arthritis as the main differential diagnosis.
1540020 Morphological evidence that activated polymorphs circulate in the peripheral blood of pati 1992 Jan Purified peripheral blood polymorphonuclear leucocytes (PMNs) from patients with rheumatoid arthritis (RA) have been found to differ from purified PMNs from normal subjects in ways that are consistent with their prior activation. However, it is currently contentious whether activated PMNs really circulate in patients with RA, or whether they are produced as an in vitro artefact of purification. Recently developed rapid leucocyte fixation and preparation technique showed that the proportion of polarised (activated) PMNs (36.9 (24.7)%, mean (SD); n = 31) was increased relative to that in control subjects (8.1 (5.6)%; n = 12). Serum cytidine deaminase levels, a biochemical marker of PMN lysis, were also increased in patients with RA (11.59 (7.26) U/ml) compared with those in controls (6.82 (3.78) U/ml), but the proportion of polarised PMNs and the levels of cytidine deaminase activity were unrelated to clinical assessments of inflammatory disease activity. Twelve patients who were not receiving drugs or who were receiving only non-steroidal anti-inflammatory drugs (NSAIDs) had more polarised PMNs than 19 patients receiving second line treatment in addition to NSAIDs (patients receiving NSAIDs, 49.6 (25.9)%; patients receiving second line treatment, 27.5 (21.1)%). Fluorescence activated cytometric analysis of CR1 and CR3 expression on PMNs from a randomly selected subgroup of patients with RA showed that the serum level of cytidine deaminase activity was correlated positively with the expression of CR1 (the C3b receptor) on the cell surface and that the proportion of polarised PMNs was positively correlated with the expression of CR3 (or CD11b/CD18), the iC3b receptor that is upregulated on activation. It is suggested that the polarised PMNs which circulate in blood samples from patients with RA represent cells which have been activated but not yet marginated, or activated cells which have marginated but subsequently returned to the circulating pool.
7740838 Discrepancy in T cell clonal expansions in synovial fluid and peripheral blood from rheuma 1995 Mar Rheumatoid arthritis (RA) is an autoimmune disease involving the synovial membrane of peripheral joints. T cells specific for self antigens may play a critical role. Identification of T cell receptors (TCR) of such specific T cell clones is very important for treatment, prevention and identification of relevant autoantigens. To identify specific T cells, TCR V beta family repertoire and the clonal expansion of T cells were analyzed in this study. The percentage of V beta 5+ or V beta 8+ cells in the synovial fluid mononuclear cells (SFMCs) was similar to that in the peripheral blood mononuclear cells (PBMCs). However, the percentage of DR+ T cells in the SFMCs was higher (p < 0.01). Analyzing the clonality of T cells in 8 V beta families (V beta 1, V beta 5, V beta 8, V beta 14, V beta 16, V beta 17, V beta 18, V beta 20), clonal expansions in CD8+ T cells from the SFMCs were found more frequently than in the PBMCs. The patterns of clonal expansions were discrepant between the SFMCs and the PBMCs even in the same patient, which suggests several inflamed tissue specific T cell clonal expansions in the SFMCs. These T cell clones might be activated by autoantigens which are not identified yet and responsible for the RA pathogenesis.
8205370 Methotrexate serum binding in rheumatoid arthritis. 1994 Mar The serum binding of methotrexate was determined by equilibrium dialysis using radiolabelled methotrexate. Methotrexate was only albumin-bound in serum. The binding was 46% in controls versus 42% in rheumatoid arthritis and 44% in cancer. Serum binding was significantly decreased by salicylate and high concentration of naproxen. Hypoalbuminemia and concomitant administration of salicylate or naproxen may influence methotrexate toxicity.
8608350 Presence of bacterial flora-derived antigen in synovial tissue macrophages and dendritic c 1995 Dec In previous studies using and animal model human bacterial flora-derived peptidoglycan Polysaccharides were shown to be arthropathic after a single subcutaneous injection. A prerequisite for proof of the hypothesis that bacterial products from the normal resident flora are involved in the immune reaction of human chronic polyarthritis of unknown aetiology is the presence of these antigens in synovial tissue. 2E9, a monoclonal antibody we developed against intestinal peptidoglycan polysaccharides was used in a histochemical study in rats and stained macrophages in the spleen red pulp. In this study human synovial tissues from 10 rheumatoid arthritis (RA) and 20 non-RA patients were stained with 2E9. We found that eight out of 10 RA patients had 2E9-positive macrophages and dendritic cells in their synovia. A significant difference was observed with the control group in which seven out of 20 were positive. No positive cells or staining of the matrix was found in the cartilage of six RA patients. These results show that exogenous bacterial antigens are present in synovial tissue macrophages and dendritic cells. It was concluded that the unknown antigen in the immune reaction in RA is not necessarily endogenous.
8823707 Bucillamine induced pulmonary injury occurs with immunoglobulin decrease. 1996 Jul We describe pulmonary involvement in 3 patients with rheumatoid arthritis treated with bucillamine. In all 3, synovitis was in remission. The common radiological characteristic was mottled dense infiltrates, in which were air bronchograms, in the bilateral central lung, sparing the periphery. Lung biopsies in 2 cases revealed organizing exudates in the alveolar ducts and alveoli, and cellular infiltration into alveoli and septa. Serum immunoglobulin (Ig) levels decreased markedly at the time of involvement. After discontinuation of bucillamine, lung injury resolved without exacerbation of synovitis and Ig levels increased. A mechanism involving decreased Ig concentration is suggested.
8162449 Urinary excretion of pyridinium crosslinks of collagen correlated with joint damage in art 1994 Jan The urinary excretion of the collagen crosslinking compounds pyridinoline and deoxypyridinoline have been determined in patients with morphologically different subgroups of OA and RA. There was no significant difference in pyridinoline or deoxypyridinoline excretion when patients with four grades of severity of OA were compared, although the median excretion of pyridinoline and deoxypyridinoline for the OA group as a whole was raised above values found in a healthy control population. Patients with severe or late (burnt-out) RA were found to have a significantly greater excretion of pyridinoline and deoxypyridinoline than patients with early (< 6 months duration) or mild RA.
8162463 Joint scintigraphy for quantification of synovitis with 99mTc-labelled human immunoglobuli 1994 Jan The ability of scintigraphy with technetium 99m-labelled polyclonal human immunoglobulin G (99mTc-IgG) to detect and quantify arthritis activity was studied in 24 patients with RA and in 10 patients with OA. The results of 99mTc-IgG scintigraphy were compared with those of scintigraphy with 99mTc-labelled hydroxymethylene-diphosphonate (HDP). The mean joint scores of 99mTc-IgG scintigraphy in RA patients with active disease were significantly higher (P < 0.001) than the mean scores in patients with inactive disease. The mean joint scores were also higher in patients with erosions compared to those in patients without erosions (P < 0.05). For 99mTc-HDP scintigraphy no significant differences were found between the mean joint scores of these patient groups. Comparison of scintigraphic results between patients with RA and OA revealed that the mean joint score of 99mTc-IgG scintigraphy was significantly (P < 0.001) higher in the patients with RA than in patients with OA, whereas for 99mTc-HDP scintigraphy this difference was not significant. These results show that 99mTc-IgG scintigraphy, when compared to 99mTc-HDP scintigraphy, is a more specific method of detecting synovitis and, also, shows differentiation between different degrees of arthritis activity in RA.
7918720 Social support, social disability, and psychological well-being in rheumatoid arthritis. 1994 Mar PURPOSE: Rheumatoid arthritis (RA) is a disease that may lead to social disability. As a consequence, the psychological well-being of RA patients can be strained. Social support is a possible moderator of the relation between social disability and psychological well-being. The focus of the present study is on the main effect versus the buffering effect of social support. METHODS: Data on 54 RA patients were gathered by means of a 2-hr interview at the patient's home. RESULTS: Receiving more daily emotional support positively related to greater psychological well-being; whereas problem-oriented emotional support negatively related to some aspects of psychological well-being. People receiving more social companionship turned out to be less depressed. CONCLUSION: The assumption was confirmed that social support has a major effect on psychological well-being. A buffering effect of social support was not demonstrated.
8670593 Diagnostic value of anti-RA33 antibody, antikeratin antibody, antiperinuclear factor and a 1996 Jul The goal of this prospective longitudinal study was to determine the serological profile of early rheumatoid arthritis (RA), and to test whether antikeratin antibody (AKA), antiperinuclear factor (APF), anti-RA33 antibody and antinuclear antibodies (ANA) had an additional diagnostic value when prescribed after rheumatoid factor (RF)-detecting methods. Sixty-nine patients with early polyarthritis suggestive of RA, seen between 1991 and 1993, were included. Five autoantibodies (i.e. RF, AKA, APF, RA33, ANA) were looked for at regular intervals. After 24 months follow-up, patients were classified as having RA (n = 49), unclassified polyarthritis (UP; n = 15) or other rheumatic diseases. Among patients with early RA, the sensitivity of these markers was 40.8% for RF, 36.7% for AKA, 28.6% for APF and 28.6% for anti-RA33. Among RF-negative RA patients, 51.7% were positive for AKA, APF, anti-RA33 antibodies and/or ANA. Positivity of the three recent markers usually persisted throughout follow-up, whereas RF was lost by 58% of patients with early, RF-positive, treated RA. Using multivariate analysis, only latex, RF test and AKA or APF had an independent and statistically significant diagnostic value for early RA. Our data suggest that RF and AKA (or APF) should be concomitantly determined for diagnosis in patients with suspected early RA.
8891972 Sauvé-Kapandji procedure for disorders of the distal radioulnar joint: a simplified techn 1996 Sep A simplified technique of the Sauvé-Kapandji (SK) procedure for disorders of the distal radioulnar joint (DRUJ) is described. The DRUJ is transfixed by a screw but is not formally exposed and fused, the periosteum of the distal ulna is not excised, and the pronator quadratus is not advanced into the pseudarthrosis. Stability of the ulna shaft is obtained by suturing the sheath of the extensor carpi ulnaris (ECU) and periosteum as a single layer firmly over the ulnar stump and pseudarthrosis. The operating time averages 20 minutes. Review of 28 wrists demonstrated relief of pain in 27; 80 degrees or greater of pronation and supination in 19 and 20, respectively; fusion of the DRUJ in 18; and ulnar carpal shift in 3. The main complications were related to screw placement and length and prominence of the ECU tendon. The simplified SK procedure reliably relieves pain and restores movement at the DRUJ.
7705874 A study on physiological changes in essential hypertension and rheumatoid arthritis with r 1995 Jan The levels of plasma cortisol, blood glucose, serum triglycerides (TG) and total cholesterol (TC) were estimated in 175 human subjects (50 normal controls, 65 having essential hypertension and 60 suffering from rheumatoid arthritis. The results showed a significant elevation in the levels of plasma cortisol and blood glucose in both the stressed clinical groups with respect to controls. Increased levels of atherogenic lipids (TG and TC) were also observed in diseased group. However, in rheumatoid arthritis the biochemical changes were comparatively more pronounced than in hypertensives. The findings in vitro reveal that rheumatoid arthritis is a relatively more chronic and late onset disorder, since the functional performance of hypothalamo-pituitary-adrenocortical (HPA) axis declines with chronicity and the efficacy of adrenocortical response to return to normalcy becomes impaired.
7506130 Anti-RA 33 antinuclear autoantibody in rheumatoid arthritis and mixed connective tissue di 1993 Sep Besides rheumatoid factor (RF), antikeratin antibodies (AKA) and antiperinuclear factor (APN), anti-RA 33 antibody has been described as a highly specific antinuclear antibody for rheumatoid arthritis (RA). In this study RA 33 antibodies were detected using Western blotting with HeLa cell nuclear extract in a group of 94 RA patients and 259 controls. Anti-RA 33 was present in 35% of 94 RA patients, with a similar frequency in RF positive (32%) and RF-negative (45%) RA patients. RA-33 antibody was also present in 60% of a group of 30 patients with anti-U1 RNP positive mixed connective tissue disease. The specificity of anti-RA 33 for RA was 84.6%. Anti-RA 33 antibody was already present in sera from 23.5% of 18 patients with RA of less than one year's duration. Anti-RA 33 antibody was the only positive immunological marker in 3/20 cases of seronegative adult RA. No correlations were found between anti-RA 33 antibody and AKA or APF. Patients with erosive RA and patients whose ESR was > or = 50 mm after 1 hour were more likely to be anti-RA 33 positive (47.6% vs 24.4% and 42.8% vs 29.4%). These results suggest that anti-RA 33 antibody, in the absence of anti-U1-RNP antibodies, can be added to the list of the helpful serological markers for rheumatoid arthritis.
1516597 Tumor necrosis factor alpha is associated with disease activity and the degree of anemia i 1992 Jul To elucidate the role of tumor necrosis factor alpha (TNF) in determining anemia of chronic disease (ACD) in rheumatoid arthritis (RA), 24 patients were studied for disease parameters, TNF serum levels and bone marrow for erythroid colony growth and compared with six controls. Serum TNF alpha was highest in ACD and correlated well with RA disease parameters. Both TNF and other RA disease parameters correlated inversely with degree of anemia. BFUe counts were lower in ACD, correlated positively with Hb and negatively with erythrocyte sedimentation rate (ESR). TNF reduced whereas anti-TNF upregulated in vitro erythroid colony counts. TNF production occurred in similar amounts in bone marrow cultures in the three groups. From these preliminary findings we conclude that ACD in RA correlates with by RA disease activity and that TNF may serve not only as an RA disease marker but also could be one of the factors mediating impaired erythropoiesis in ACD in active RA.
8093497 Influence of non-inherited maternal HLA antigens on occurrence of rheumatoid arthritis. 1993 Jan 23 Many HLA-associated diseases occur in patients not carrying the putative predisposing antigen. The suggestion that this might be due to disease heterogeneity is not sufficiently supported by available data. We hypothesise that HLA-DR4-associated genetic susceptibility to rheumatoid arthritis is due to an effect of DR4 on T-cell receptor repertoire expression and that the presence of antigen in the mother is capable of producing this effect in her children, even when DR4 is not inherited by them. To investigate this possibility we HLA typed 94 rheumatoid arthritis patients and their parents and 86 control families. An increased frequency, compared with controls, of non-inherited maternal HLA-DR4 was found predominantly in the mothers of DR4-negative patients. Unexpectedly, we also found an increased frequency of non-inherited maternal HLA-DR6 and a decreased frequency of non-inherited maternal HLA-DR3 in the mothers of DR4-positive patients. The results of our analyses are consistent with our hypothesis.