Browse

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

ID PMID Title PublicationDate abstract
8741695 [Expression of Fas/Fas ligand and proto-oncogenes in rheumatoid synovial tissues]. 1996 Jul Expression of Fas antigen and Fas ligand (-L) were observed in synovial tissue from rheumatoid arthritis (RA) patients, whereas in only a few cells expressed these molecule osteoarthritis synovial tissue. Fas-L was expressed on CD45RO, CD4, CD8 or CD56 positive cells in RA synovial tissue. Moreover, 10 to 30% of synovial cells expressing Fas antigen were observed to be identical with apoptotic synovial cells and Fas expression was closely related to c-fos and c-myc. These findings suggest that activated T cells and natural killer cells infiltrating into the RA synovium may play an important role in the induction of apoptosis of RA synovial cells through Fas/Fas-L interactions.
7517675 Tenascin distribution in articular cartilage from normal subjects and from patients with o 1994 Jul OBJECTIVE: To determine whether tenascin is present in normal and diseased human cartilage. METHODS: Immunohistochemical and biochemical assays with a monoclonal antibody against all tenascin isoforms (BC-4) were used. RESULTS: Cartilage samples from osteoarthritis and rheumatoid arthritis patients contained increased amounts of tenascin compared with the levels in normal cartilage. Human fetal cartilage was also found to contain tenascin. In normal cartilage explants treated with interleukin-1 beta, tenascin was present in pericellular areas of all layers. Immunolocalization studies revealed that tenascin was most abundant in the superficial layers of osteoarthritic cartilage. Western blot analysis performed from dissociative extracts of diseased cartilage confirmed the presence of subunits of the native molecule. CONCLUSION: Tenascin is increased in arthritic cartilage and is weakly expressed in normal cartilage.
9569808 Antistreptolysin O, rheumatoid factor and C-reactive protein determination in patients wit 1996 Sep Recurrent oral ulcer (ROU) is a common disease whose the etiologic factors have not yet been identified. Although the autoimmune mechanism due to streptococcal antigens may be involved in this disease, serum immunoglobulins are reported to be higher than normal controls in various phases of ROU. Oral ulcers are one of the criteria in the diagnosis of some systemic diseases such as Wegener's granulomatosis, Behçet's syndrome, suppurative arthritis, Reiter's syndrome and neutropenias. Any patient with recurring oral ulcers should be evaluated medically for the possible presence or future development of serious systemic diseases. In this study of the 58% of the ROU patients who had positive ASO values, only one female patient had a moderate increase: ++ASO(= 400 IU), the rest had a slight increase: +ASO(= 200 IU). In the control group only 3 female subjects had +ASO (= 200 IU). The aim of this study was to determine whether there is any relationship between ROU and rheumatoid arthritis. Patients with ROU were examined for antistreptolysin O, rheumatoid factor and C-reactive protein and compared to healthy controls.
7869301 Analysis of the genes encoding the variable regions of human IgG rheumatoid factor. 1994 Nov OBJECTIVE: To better understand the immunoglobulin variable (V) region repertoire of rheumatoid factors (RF). METHODS: We characterized the heavy (H) and light (L) chain gene segments utilized in a monospecific IgG RF secreting hybridoma (AEE111F) which were derived from a patient with rheumatoid arthritis (RA). The hybridoma was established by fusion of a mouse myeloma cell line with bone marrow derived mononuclear cells from a patient with RA. First strand complementary DNA (cDNA) was generated and used for a polymerase chain reaction amplification of the H and L chain V domains. The amplified V domains were sequenced and compared with an extensive database of germline and cDNA V gene segments. RESULTS: The VH sequence was found to be 96% homologous to a previously described fetal VH3 cDNA (60P2). The VL sequence was also highly homologous to the previously described V lambda II gene (96%) derived from a patient with systemic lupus erythematosus which correlated with an 8.12 idiotype (Id), and to an antibacterial antibody against the Haemophilus influenzae type b capsular polysaccharide (94.7%). CONCLUSION: The overlap among this RF VL gene and the 2 reported V lambda sequences of antibodies that expressed anti-DNA related Id and an environmental pathogen specificity suggests that a part of the IgG RF isolated from patients with RA may thus be derived from the physiological natural antibody repertoire during an abnormal immune response and then develop high affinity, monospecific RF by the selection of an antigen driven mechanism.
1339917 Effects of methylcobalamin (vitamin B12) on in vitro cytokine production of peripheral blo 1992 Recently in Japan, one form of vitamin B12, methylcobalamin also known as methyl B12, has attracted the attention of physicians as a therapy for patients with rheumatoid arthritis. However, its immunological actions in vivo are still unknown. In this study, we induced the in vitro production of such cytokines as interleukin-6 (IL-6), interferon-gamma (IFN-gamma), and interleukin-1 beta (IL-1 beta) by adding various mitogens (phytohemagglutinin:PHA, concanavalin A: ConA, or pokeweed mitogen:PWM) as well as recombinant interleukin-2, and we investigated the effects of methyl B12 (final concentration, 8-8,000 ng/ml) on the production of these cytokines by peripheral mononuclear cells. As compared to the controls, IL-6 production induced by PHA and ConA on Day 4 of the culture was suppressed by an average 60-70% when methyl B12 (80-8,000 ng/ml) was added to the medium. IFN-gamma production decreased dose-dependently with methyl B12, i.e., it decreased to 46% of the control when this production was induced by rIL-2, and decreased to 56-66% when it was induced by mitogens. The effect of methyl B12 on IL-1 beta production on Day I of the culture was small. These findings indicate that methyl B12 suppresses mainly the cytokine production of T lymphocytes. Such suppressive effects as shown in the in vitro situation are expected to be expressed also in vivo in patients with rheumatoid arthritis, especially at articulation lesion sites.
7586777 Folic acid and cyanocobalamin levels in serum and erythrocytes during low-dose methotrexat 1995 Jul OBJECTIVE: To compare folic acid (FA) levels in patients being treated with methotrexate (MTX) with those of untreated patients in order to investigate potential folate depletion by MTX and its possible relationship to the drug's efficacy. METHODS: In 33 patients on low-dose MTX therapy and in 24 controls, FA and cyanocobalamin (B12) levels were determined in serum and red blood cells (RBC). In addition, MTX levels in the RBC and serum were measured, and clinical and laboratory measures of disease activity were evaluated. RESULTS: MTX treated patients had lower FA levels than controls (median 4.36 vs 7.37 ng/ml, p < 0.001). A significant correlation between serum FA and MTX/RBC (p < 0.01) and between the weekly dose and MTX/RBC (p < 0.01) was seen. There was apparently no correlation between FA and the cumulative total MTX. MTX patients had lower B12/RBC levels than the controls (p < 0.001); the serum levels of B12 were not different. Clinical features, ESR and CRP did not correlate with FA, B12 or MTX levels. CONCLUSIONS: The degree of folate depletion during MTX therapy depends primarily upon the weekly administered dose. Folate depletion may be related to B12 deficiency in RBC. Since FA levels were not related to parameters of disease activity it is conceivable that MTX does not exert its action in RA primarily by inhibiting dihydrofolatereductase. Therefore, additional folate compounds, if necessary, should not lead to a reduction in the efficacy of MTX.
8299250 Relationship between blood and joint tissue DHEAS levels in rheumatoid arthritis and osteo 1993 Nov To assess the relationship between blood and tissue steroid levels, cortisol and dehydroepiandrosterone sulphate (DHEAS) were measured by radioimmunoassay (RIA) in blood and joint tissues from a group of patients with RA (N = 29) ranging in age from 26 to 80 years (mean 63, SD: 13) and another group with secondary osteoarthritis (OA; N = 23), ranging in age from 47 to 86 years (mean 66, SD: 9), all of whom were scheduled for surgical correction of joint dysfunction. Seventeen of the RA patients were on steroid treatment at the time of the study. Assessing all the patients together, it was found that the tissue concentrations of DHEAS very closely paralleled the blood levels (r = 0.875; p < 0.001). The mean blood and tissue concentrations of DHEAS were found to be significantly reduced in RA, compared to those in OA (geometric means 540 vs. 2100 nmol/l blood, respectively, and 160 vs. 420 nmol/kg tissue, p < 0.001). Individual data indicated, however, that: (a) 3/29 patients with RA exhibited normal levels; (b) the reduction was more accentuated in those patients on steroid treatment; and (c) 5/23 patients with OA, who were treated for cardiovascular disorders, also had reduced DHEAS levels. Significant differences were not found between the mean cortisol levels in RA and those in OA, nor was there a correlation between the blood and tissue levels of this steroid. The possible influence of reduced DHEAS levels on immune-mediated diseases and/or pathophysiology is unknown, and needs to be investigated.
7473465 Sex hormone status and bone mineral density in men with rheumatoid arthritis. 1995 Aug OBJECTIVE: Sex hormone status has been proposed as an important determinant of low bone mineral density (BMD) in both men and women. Our objective was to study the relationship between sex hormones and BMD in patients with rheumatoid arthritis (RA), and how steroid therapy affects both. METHODS: We studied 99 men with RA to assess their BMD and sex hormone status. A comparative group of 68 age paired men was used. We made comparative tests, linear correlations, and multiple regression analysis. RESULTS: We found significant reductions in lumbar BMD (p = 0.0005), femoral BMD (p < 0.0005), salivary testosterone (p = 0.01), androstenedione (p = 0.007), and dehydroepiandrosterone sulfate (DHEAS) (p = 0.03) in patients with RA. In contrast, serum testosterone concentrations were normal. Salivary testosterone showed correlation with femoral BMD (r = 0.36; p < 0.001). By multiple regression analysis, weight, serum testosterone concentrations, and the cumulative dose of corticosteroids were significant predictors of lumbar BMD (r = 0.41; p = 0.001). Weight, age, androstenedione concentrations, and the cumulative dose of corticosteroids were the significant predictors of femoral BMD (r = 0.79; p < 0.0005). CONCLUSION: We confirm there is reduced BMD in men with RA; corticosteroids contribute, but are not the only factor in the pathogenesis of low BMD in patients with RA; we found decreased levels of androstenedione, DHEAS, and salivary testosterone in men with RA; and salivary testosterone, as with free testosterone, is correlated with BMD in patients with RA, with lower levels contributing to low BMD.
7533784 Cartilage and bone metabolism in rheumatoid arthritis. Differences between rapid and slow 1995 Mar Serum concentrations of specific cartilage and bone molecules reflecting tissue turnover were measured in two well-defined patient groups with early rheumatoid arthritis with distinctly different disease outcome to see if early differences in their levels are prognostic of the rate of joint destruction. Compared with a matched normal population, increased concentrations of cartilage oligomeric matrix protein (COMP) were found in all patients who developed rapid hip joint destruction. In contrast, levels of a putative marker of cartilage aggrecan synthesis, the chondroitin sulfate epitope 846, were increased only in patients with slow joint destruction. Levels of bone sialoprotein (BSP) were increased in both groups, as were levels of the C-propeptide of type II procollagen (CPII), a marker of collagen II synthesis. The increased concentrations of the 846 epitope in patients with slow joint destruction suggest increased aggrecan synthesis. The low levels of the 846 epitope in patients with rapid joint destruction, concomitant with elevated levels of CPII, suggest a selective increase in collagen synthesis. The elevated BSP levels indicate an increased bone turnover in both groups. Thus elevated serum levels of COMP may indicate an unfavorable prognosis for rapid joint destruction, whereas elevated 846 epitope indicates a more favorable prognosis.
8060082 Radiation necrosis overlying the ankle joint after injection with yttrium-90. 1994 May A 35-year-old woman with rheumatoid arthritis presented with radiation necrosis and an open wound overlying her ankle joint, 8 months after injection with yttrium-90 to facilitate radiosynovectomy. This problem was successfully treated by surgical excision of the area of radiation damage and closure with a fasciocutaneous flap.
7960501 Yersinia enterocolitica: an inducer of chronic inflammation. 1994 The aim of the present study was to elucidate the connection between yersiniosis and chronic inflammation. During the period 1974-83, Yersinia enterocolitica infection was diagnosed in 458 hospitalized patients by antibody response, or isolation. The patients were followed for 4-14 years (1987); 160 were readmitted with chronic disease. Fifty-three patients had persistent joint complaints, 18 developed ankylosing spondylitis, 14 rheumatoid arthritis, and 17 iridocyclitis. Thirty-eight patients suffered from chronic abdominal pain, and another 28 from chronic diarrhoea. Two who underwent proctocolectomy microscopically had ulcerative colitis. Eleven patients developed neurological disease; others developed conditions such as chronic nephritis, thyroid disease, insulin-dependent diabetes, etc. Chronic hepatitis, found in 22 patients, was significantly correlated with positive test for antinuclear antibody and rheumatoid factor, and with death. Several patients developed chronic multiorgan disease, probably with chronic hepatitis as pivot. Regarding the whole material, the difference between observed and expected cumulative survival rates remained significant for 8 years (0.9189 < 0.9456; p < 0.025), indicating a substantial impact on long-term survival exerted by chronic yersiniosis.
9036722 [Possible effect of hormones on immune and inflammatory processes in female patients with 1996 The influence of gender on the prevalence of rheumatoid arthritis (RA) is well known. We examined 40 female patients with RA to show the possible influence of androgen hormones on inflammation and immune system. We measured blood count, blood sedimentation rate, C-reactive protein routinely and free and bound testosterone, dehydroepiandrosterone-sulfate (DHEA-S), prolactin, insulin like growth factor-1 (IGF), IgA-rheumatoid factor (IgA-RF) and the monocyte marker CD 14 of radioimmunoassays and enzymeimmunoassays. The female patients with RA had lower androgen levels correlating with higher inflammatory markers which are not rising significantly with higher age. The significantly raised IgA-RF with abnormal low testosterone levels points out a poor prognosis for developing joint erosions. The simultaneously reduced levels of prolactin may be rather caused by cytokines and could have additional connections to the anemia in RA. Somatomedin correlated inversely to the degree of inflammation, measured by BSR, CRP and CD 14, a fact which could indicate a reduced, Somatomedin-induced, synthesis in matrix and collagen of cartilage in "active" RA. The results point to the existence of a reciprocal connection of the endocrine system with the immune system.
8927383 [The rheumatic forefoot]. 1996 Aug The prevalence of rheumatic forefoot arthritis is estimated at 85-95%. Early synovitis of the metatarsophalangeal (MTP) joints is frequently neglected or overlooked. The disease leads to depression of the forefoot arch, dislocation of the MTP joints and hallux valgus with severe metatarsalgia. Operative treatment may give good results in 77-91% of cases. Our preferred treatment consists of resection arthroplasties for the smaller toes and use of Swanson spacer for the big toe, extensive capsular and tendon release from the dorsal approach, reduction of the first metatarsal bone, relocation of the extensor hallucis tendon and postoperative corrective dressing for 6-12 weeks. With this technique, we obtained 36 good results out of 46 forefoot reconstructions, the mean observation period being 30 months.
7561350 [The solubility of calcium pyrophosphate dihydrate crystals]. 1995 Jul The solubility of calcium pyrophosphate dihydrate crystals (CPPD crystals), which cause pseudogout, was studied in vitro and vivo. The in vitro experiment using 0.1 M tris buffer and 0.2 M glycine buffer indicated that changes in pH and pyrophosphatase activity played a major role in the solubility of CPPD crystals. An experiment using the synovial fluid from patients with pseudogout, rheumatoid arthritis, and from those with osteoarthritis suggested that changes in the synovial fluid pH due to inflammation affected the solubility of these crystals. In addition, an experiment using the air pouch in rat showed that inflammation due to the CPPD crystals was maximum at about 9 hours after CPPD injection, and that inflammatory cells appearing at this time then had a major influence on the crystals' solubility. From these results, it appeared that CPPD crystals released into the joint cavity were mostly dissolved by inflammatory cells, but that crystal dissolution was also affected by changes in the synovial fluid itself, particularly by a change in pH.
8849378 Pancytopenia secondary to methotrexate therapy in rheumatoid arthritis. 1996 Feb OBJECTIVE: To assess the frequency of methotrexate (MTX)-induced pancytopenia in rheumatoid arthritis (RA). METHODS: A MEDLINE literature search was conducted to identify articles published during the last 15 years (1980-1995) that presented data on MTX-associated pancytopenia. Two case reports of our own experience are also presented. In addition, articles that examined risk factors associated with MTX-related pancytopenia were identified. RESULTS: A total of 70 patients with pancytopenia related to MTX therapy were identified (68 reported in the literature, 2 from our own experience). Sixty-one of the patients were described in published case reports, 7 patients were from 5 long-term prospective studies. In many of these cases, predisposing factors for the development of pancytopenia were described. The 5 long-term prospective studies reported toxicity data on patients who had been treated with MTX for at least 13 weeks. A total of 511 patients were included in the prospective trials, yielding an overall incidence of pancytopenia of 1.4% (7 of 511). Of the 70 cases reported, 12 patients died (17%). Most of them had impaired renal function, hypoalbuminemia, concurrent infection, and/or concomitant medication with more than 5 drugs. The minimal cumulative MTX dose leading to fatal pancytopenia was 10 mg, observed in one of our patients. CONCLUSION: Pancytopenia is not an uncommon side effect of low-dose pulse MTX therapy in RA. It can lead to serious complications, including death.
8345790 Apolipoproteins A-I and B and cholesterol in synovial fluid of patients with rheumatoid ar 1993 Jul Synovial fluid (SF) of patients with rheumatoid arthritis (RA) has been noted to contain cholesterol crystals and increased amounts of cholesterol compared with normal SF. SF, plasma apolipoproteins (apos) A-I and B, and cholesterol in 12 untreated classic RA patients (inflammatory arthritis) and eight untreated degenerative joint disease ([DJD] noninflammatory arthritis) patients were analyzed. Results showed that mean apo A-I, apo B, and cholesterol levels of RA SF were significantly higher than those of DJD SF (apo A-I, P = .004; apo B, P = .0008; cholesterol, P = .0004). Regression analyses of plasma and SF apo A-I and apo B (r = .72, P = .008 and r = .63, P = .02, respectively) suggested an increased permeability for these lipoprotein constituents across RA synovial membrane that was not observed in DJD synovial membrane. These data suggest that RA synovium but not DJD synovium is more permeable to major apoproteins of low- and high-density lipoproteins (LDL and HDL). These apolipoproteins have been shown to influence the immune response and may therefore be involved in the pathogenesis of RA.
8181256 Antibodies to heat shock protein 65 kD in type 1 diabetes mellitus. 1994 Jan To determine whether antibodies to mycobacterial heat shock protein of 65 kD molecular weight (hsp 65) could be important in the pathogenesis of Type 1 diabetes we tested patients before and at diagnosis of diabetes, as well as patients with rheumatoid arthritis. Using ELISA, increased hsp 65 antibodies were detected in 2 of 8 pre-diabetic twins, 1 of 13 newly diagnosed untreated diabetic patients and 3 of 10 rheumatoid arthritis patients. Levels of hsp 65 antibodies in pre-diabetic twins, median (range), 0.25 (0.104-1.904) and newly diagnosed diabetic patients (mean +/- SD) (0.299 +/- 0.220), did not differ significantly either from each other or from their control subjects (0.134 +/- 0.123). In contrast, levels of hsp 65 antibodies in rheumatoid patients (0.59 +/- 0.42) were significantly higher than in their control subjects (0.21 +/- 0.18; p = 0.02). Of twins studied prospectively before diagnosis, at diagnosis but before insulin treatment, and soon after diagnosis, three of four had hsp 65 antibodies at some stage. We conclude that serological immunity to mycobacterial hsp 65 can occur in Type 1 diabetes, but it is neither a characteristic nor a specific feature of the disease.
8472870 Autoimmune T-cell recognition sites of human thyrotropin receptor in Graves' disease. 1993 Mar Five overlapping synthetic peptides representing two regions of thyrotropin (TSH) binding sites of human thyrotropin receptor (TSHR) (peptides 12-30, 24-44, 308-328, 324-344 and 339-364) were investigated for their ability to cause proliferation of peripheral blood lymphocytes (PBL) from eight patients with Graves' disease. The same experiment was done using PBL from four cases with Hashimoto's thyroiditis, two cases with subacute thyroiditis, two cases with rheumatoid arthritis (RA) and eight normal volunteers. PBL obtained from each patient with Graves' disease responded to one or more of peptides 12-30, 24-44, 308-328 and 324-344, while peptide 339-364 had no stimulating activity. The level of stimulating activity of each of the four aforementioned TSHR peptides varied from patient to patient. None of the five TSHR peptides caused the proliferation of PBL from patients with Hashimoto's thyroiditis, subacute thyroiditis, or RA and from normal volunteers. The results indicate that the proliferation of PBL by TSHR peptides is specific in patients with Graves' disease and that the regions of TSHR which are involved in the binding to TSH are also the target of autoimmune T-cell recognition in Graves' disease. The difference in T-cell response from patient to patient could be explained by genetic regulation toward each autodeterminant.
7796664 [The role of intestinal permeability in the pathogenesis of ankylosing spondylitis]. 1995 Feb By use of low molecular weight polyethlene glycol (PEG400) as tracer, a revised Chedwick method with capillary gas chromatography was used to examine the intestinal permeability in 49 subjects including patients with ankylosing spondylitis (AS) and rheumatoid arthritis (RA) and healthy controls. Recovery percentage, maximal recovery percentage [Rmax(%)] and Rmax(w) were used to find the effect of bowel permeability in the pathogenesis and disease flare up of AS, as well as the role of HLA-B27 for the bowel permeability. The results showed that in AS group, the recovery of first component (242D) was higher and the Rmax(%) was lower than those in the controls. No statistical difference was found with other indexes. The results indicated that bowel permeability is not elevated in AS. The passage of enteral bacteria antigen into the host may not result from the process of nonspecific penetration. We postulate that there may somehow be a process of "active transportation" in the pathogenesis of AS. More studies of the process are necessary to clarify its importance in the early stage of AS.
8102225 Alkaline phosphatase isoenzyme activities in rheumatoid arthritis: hepatobiliary enzyme di 1993 Jul OBJECTIVES: Hyperphosphatasaemia has been observed occasionally in patients with rheumatoid arthritis (RA), and it has been suggested that the serum alkaline phosphatase (ALP) level is related to the activity of the disease. Therefore, the relationship between serum ALP and RA was studied. METHODS: The serum activities of hepatobiliary enzymes (ALP isoenzymes, gamma-glutamyltranspeptidase (GTP), leucine aminopeptidase (LAP), aspartate aminotransferase (AST), and alanine aminotransferase (ALT)), immunoglobulins, RA haemagglutinin test (RAHA), C reactive protein (CRP), and erythrocyte sedimentation rate (ESR) were observed in 288 patients with rheumatoid arthritis. RESULTS: Serum biliary ALP (ALP1) activity was detected in 31.6% of the patients. In patients positive for ALP1 the respective values of total ALP (ALPt) (p < 0.001), liver ALP (ALP2) (p < 0.001), bone ALP (ALP3) (p < 0.05), gamma-GTP (p < 0.001), LAP (p < 0.001), immunoglobulins IgG (p < 0.01), IgA (p < 0.01), and IgM (p < 0.01), RAHA (p < 0.001), CRP (p < 0.001), ESR (p < 0.001), and articular index (p < 0.001) were significantly higher than in patients who did not have ALP1. Significant Spearman's rank correlations (rs) were demonstrated between serum ALP2 level and the respective values of ALPt (rs = 0.9128, p < 0.001), ALP1 (rs = 0.4443, p < 0.001), ALP3 (rs = 0.5898, p < 0.001), gamma-GTP (rs = 0.2903, p < 0.001), LAP (rs = 0.3093, p < 0.001), IgA (rs = 0.2299, p < 0.01), IgM (rs = 0.1773, p < 0.05), RAHA (rs = 0.2420, p < 0.01), CRP (rs = 0.3532, p < 0.001), ESR (rs = 0.4006, p < 0.001). the articular index (rs = 0.4006, p < 0.001). However, no significant difference or correlation was noted for either AST or ALT. In many patients who showed abnormal hyperphosphatasaemia, hepatobiliary enzyme dissociation was observed: levels of ALPt (in 12.8%), ALP1 (in 31.6%), ALP2 (18.8%), gamma-GTP (in 4.3%), and LAP (in 19.3%) were abnormally high, but both AST and ALT were within normal limits. CONCLUSION: These findings are considered to be characteristic of RA, and suggest the existence of latent or subclinical hepatobiliary involvement and an association between the expansion of hepatobiliary involvement and the mechanism of disease activation. Thus measurement of the serum levels of ALP and its isoenzymes in RA is considered to be important.