Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 1491387 | Erythroid abnormalities in rheumatoid arthritis: the role of erythropoietin. | 1992 Nov | Erythroid alterations were studied in 136 patients with rheumatoid arthritis (RA). Anemia was present in 75 cases. A definite diagnosis was determined in 65. The most frequent anemia was that of chronic disease (ACD) (43 cases); 14 patients with ACD presented with moderate to severe anemia. Prevalence of deficiencies were also high (15 cases had iron deficiency anemia, IDA). Serum erythropoietin levels were different in patients with RA compared with a healthy control group (p < 0.00001). Serum erythropoietin was increased in ACD (49 +/- 28.8 U/l) with respect to both RA (38.6 +/- 12.7 U/l, p = 0.0036) and controls (18.2 +/- 7.6 U/l, p < 0.00001). Although hemoglobin (Hb) was similar in ACD and IDA, serum erythropoietin in ACD was lower than in IDA (p = 0.01). There was a negative relationship between Hb and serum erythropoietin in ACD (r = -0.42, p = 0.005). In conclusion, almost 50% of patients with RA have anemia and ACD is the most frequent. As serum erythropoietin in ACD is blunted, patients with moderate to severe ACD are possible candidates for erythropoietin treatment. | |
| 8861742 | Inflammatory and immunological parameters of disease activity in rheumatoid arthritis pati | 1996 Mar | The objective of this study was to analyze the anti-inflammatory effect of minocycline in rheumatoid arthritis. Serum samples of 65 RA patients who completed a 26-week randomized double-blind trial of minocycline (100 mg twice a day) versus placebo were studied. In this trial some clinical parameters and in particular the acute phase response decreased significantly in the minocycline-treated group. Serum levels of albumin and interleukin-6 (IL-6) were compared with CRP levels in order to study the acute phase response. Furthermore, rheumatoid factor (RF) and total immunoglobulin isotypes as well as serum levels of soluble interleukin-2 receptor (sIL2-2R) were determined in order to study immunological parameters of the disease. Immunoglobulins and cytokines were measured by ELISA. Serum levels of albumin remained stable, whereas serum CRP levels decreased both in the minocycline- and in the placebo-treated group. Serum levels of IL-6 decreased in the minocycline-treated group only and this decrease was positively correlated with the decrease in CRP levels. Minocycline significantly decreased serum IgM-RF, IgA-RF, total IgM and total IgA levels. In addition the ratio of IgM-RF/total IgM decreased in the minocycline-treated group. No such changes were observed in the placebo-treated group. The anti-inflammatory effect of minocycline in RA patients may be due to the reduction in the synthesis of IL-6 and rheumatoid factor. | |
| 8761183 | Anti-ganglioside antibodies in patients with rheumatoid arthritis complicated by periphera | 1996 Aug | Gangliosides are a diverse class of glycolipids found in the plasma membrane of mammalian cells and are particularly abundant in cells of the nervous system. Serum antibodies to gangliosides have been detected in various neurological disorders with some evidence that they play a pathogenic role. In this study, we have investigated whether anti-ganglioside antibodies were elevated in a group of patients with rheumatoid arthritis (RA) who developed peripheral neuropathy (PN). An ELISA technique was used to test sera from 28 patients with RA and PN. 38 RA patients without PN and 20 normal controls for the presence of IgG and IgM anti-GM1 and sulphatide antibodies. The patients with RA and PN had higher pain scores (P < 0.005), more extra-articular features (P < 0.05), higher erosive scores (P < 0.0001), lower haemoglobin (P < 0.005), higher ESR (P < 0.001) and were more often on disease-modifying drugs (P < 0.05). Twelve RA patients with PN (43%), but only two RA controls (5%), had positive titres against one or more gangliosides (P < 0.001). The neurologic disability score (NDS) correlated with RA duration (P < 0.05), and with levels of IgM anti-GM1 (P < 0.001) and IgM anti-sulphatide (P < 0.05) antibodies. We conclude that PN is more common in patients with severe rheumatoid disease, and a significant proportion have elevated levels of anti-ganglioside antibodies. | |
| 1422258 | Inflammatory cytokines and enzymes in synovial fluid of patients with rheumatoid arthritis | 1992 | Cytokines and lysosomal enzymes, which are produced by inflammatory cells, play a role in inflammation. We have found that synovial fluid (SF) in rheumatoid and septic arthritis contained a large number of white blood cells (WBCs) and high levels of cytokines and enzymes, while in contrast the SF of osteoarthritis and traumatic arthritis did not contain significant amounts. Measurements of WBCs, cytokines and enzymes in SF are useful for evaluating clinical disease activity. Assays for WBCs and enzymes are simple and rapid when compared to those for cytokines. | |
| 8697652 | Positive and negative association of HLA-DR genotypes with Japanese rheumatoid arthritis. | 1996 Jan | OBJECTIVE: To clarify the relationship between the HLA-DR genotype and susceptibility to rheumatoid arthritis (RA) in Japanese patients. METHODS: HLA-DR typing and DRB1* genotyping were carried out by PCR and PCR-SSCP (single stranded DNA conformation polymorphism), respectively. RESULTS: In RA, the prevalence of HLA-DR4 was significantly higher (57.3%, p < 0.05). In particular, DRB1*0405 was predominantly higher (46.9%, p < 0.05) and DRB1*0401 was also increased although not significantly. HLA-DR8, especially DRB1*0802, was significantly lower (1.0%, p < 0.01). RA patients homozygous for DRB1*0405 showed slightly higher values for the erythrocyte sedimentation rate, gamma-globulin, and IgG, as well as positivity for rheumatoid factor and high titers for the Waalar-Rose test, and a decrease in the albumin/globulin ratio, albumin, and hemoglobin in comparison to patients without RA susceptibility genes, although the difference for each of these parameters was not significant. CONCLUSION: DRB1*0405 and DRB1*0802, which are both rare alleles in Caucasians, are positively and negatively correlated, respectively, with the pathogenesis of RA in Japan. | |
| 8129454 | Does parvovirus B19 have a role in rheumatoid arthritis? | 1994 Feb | OBJECTIVES: To determine whether parvovirus B19 (B19) infection is associated with rheumatoid arthritis (RA). METHODS: The polymerase chain reaction was applied to serum, cells isolated from synovial fluid, and synovial fluid. Enzyme immunoassay technique was used to detect antibodies against B19. RESULTS: Of 142 patients with early RA (onset of disease under one year) and 67 control patients, serological evidence of recent parvoviral infection was found in 4/135 and 2/62, respectively. However, no evidence for the presence of parvoviral DNA was observed in 18 synovial fluids, 21 samples of synovial fluid granulocytes or 40 sera, all obtained from 65 patients diagnosed with early RA. CONCLUSION: Although there is published evidence of chronic rheumatoid-like arthropathy following acute parvovirus infection, our findings do not support the involvement of B19 in the aetiopathogenesis of RA. | |
| 1592206 | Endogenous retroviruses: potential etiologic agents in autoimmunity. | 1992 May | The genomes of all organisms, from yeast to humans, contain thousands of endogenous retroviruses (ERV). In most species all or almost all ERV are noninfectious, but some ERV retain open reading frames capable of encoding proteins. RNA and proteins derived from ERV are expressed in humans and other species. Until recently, there was little evidence that this ERV expression resulted in any immunologic effects. Recent studies make it increasingly clear that some ERV have important immunologic effects. The immune effects of ERV expression raise the question of a possible pathogenic role in idiopathic autoimmune diseases. Interest in this question has been heightened by the observation that some infectious retroviruses cause manifestations of autoimmunity. Nonetheless, attempts to isolate infectious retroviruses from patients with idiopathic autoimmune diseases have generally failed. The possible role of ERV in idiopathic autoimmune diseases has not yet been fully explored. This review focuses on the known and the potential immune effects of ERV, especially as they may relate to autoimmune diseases. | |
| 1342474 | [Anticardiolipin antibodies in connective tissue diseases]. | 1992 Mar | The incidence of anticardiolipin (ACL) antibodies in connective tissue disorders other than systemic lupus was investigated in 113 subjects: 68 had rheumatoid arthritis, 23 primary Sjogren syndrome and 22 had systemic sclerosis. VDRL, thromboplastin time and determination of IgG and IgM ACL antibodies (ELISA) were performed in all subjects. Overall, 45% of patients were positive for ACL antibodies, mostly of the IgG variety (90%). No differences were observed among the investigated diseases. Positive ACL antibodies were not related to evidence of antiphospholipid syndrome nor to clinical characteristics of the different diseases. These results confirm that ACL antibodies may be present in connective tissue disorders other than systemic lupus, but they do not predict the development of antiphospholipid syndrome nor help to characterize the severity of the disease. | |
| 8235496 | Frequency of amyloidosis in Estonian patients with rheumatoid arthritis. | 1993 | Occurrence of secondary amyloidosis in hospitalized Estonian patients suffering from rheumatoid arthritis was studied using subcutaneous fat aspiration biopsies. Only 47 out of 59 samples included fat, and amyloidosis deposits were found in 11 of these (23%). The high frequency of amyloidosis may be due to selection of the most severe cases in the hospital. | |
| 8128543 | [Autoimmune diseases--principles and selected examples]. | 1993 Dec 1 | Autoimmune diseases present themselves as syndromes of different dysfunctions of the immune system due to multiple disturbances of immuninformation and regulation. Because of the lifelong persistence of the auto-antigen, chronic progredient diseases develop with a variety of symptoms and different stages within the clinical course. It may be that at first glance symptoms of lesser importance, like skin disorders or proteinuria, can be markers of a systemic manifestation of an immunopathy. The underwriting of proposal ought to be based on information of the own and family history as well as on recent clinical and serological findings and on the possible involvement of other organs. | |
| 7836027 | Dynamic training and circulating neuropeptides in patients with rheumatoid arthritis: a co | 1994 | This study aimed at evaluating the effects of a dynamic physical training programme on circulating levels of corticotropin-releasing hormone (CRH), beta-lipotropin (beta-LPH), and beta-endorphin (beta-EP) after high-intensity training for 6 weeks (60 min twice a week) and after low-intensity training (home-training) for another 6 months in patients with rheumatoid arthritis (RA) and in healthy subjects. Additionally, differences in neuropeptide levels between the two groups were studied. A total of 30 patients with RA were randomly allocated to the study, 15 in the training group (TG) and 15 in the control group (CG). In addition, 20 healthy subjects (10 in TG; 10 in CG) participated. In addition to the biochemical analyses, the following variables were assessed for the RA group: pain and disability (Stanford health assessment questionnaire), joint tenderness (Ritchie articular index), disease activity, muscle function, aerobic capacity, sociodemographic data and attitudes. The results obtained at the start revealed significant differences (p < 0.05) between RA patients and healthy subjects concerning CRH levels, RA patients showing the lower levels (RA-group Md = 24 pmol/L, healthy group Md = 29 pmol/L). No significant differences concerning beta-LPH and beta-EP were found here. After the high-intensity training period, a significant increase of the CRH levels were found for the RA-TG (pretest Md = 24 pmol/L, after 6 weeks Md = 27 pmol/L, p < 0.05). No such results were found for the healthy-TG or the control groups. Concerning beta-EP, significant differences between the RA-TG and healthy-TG were found after the training. RA patients generally showing higher levels as compared with the healthy (RA-group Md = 42 pmol/L, healthy group Md = 36 pmol/L, p < 0.05). The same pattern was found for the beta-LPH levels. In conclusion, the effects of physical training on circulating neuropeptides remain still incompletely examined, and there is no definite answer to the question whether increased beta-EP levels are good or bad. | |
| 1380987 | Activation and differentiation of myelomonocytic cells in rheumatoid arthritis and healthy | 1992 Jul | We analyzed expression of HLA-DR and CD14 molecules on myelomonocytic cells and its regulation by various inflammatory cytokines in 6 patients with rheumatoid arthritis (RA) and 4 healthy individuals who had undergone bone marrow aspiration. At start of the bone marrow culture there was a significantly higher number of HLA-DR and CD14 positive bone marrow mononuclear cells in patients with RA than in normals. In addition, RA bone marrow mononuclear cells expressed an up to 10-fold higher mean density of both molecules than normal bone marrow mononuclear cells during the whole culture period of up to 14 days. The effect of the cytokines interferon-gamma (IFN-gamma), tumor necrosis factor alpha (TNF alpha), granulocyte monocyte colony stimulating factor (GM-CSF) and interleukin 1 (IL-1) on the expression of CD14 or HLA-DR was different: IFN-gamma strongly upregulated HLA-DR expression and down-regulated CD14 expression while TNF alpha, GM-CSF and IL-1 mainly stimulated CD14 expression on bone marrow mononuclear cells. Our data suggest that RA bone marrow mononuclear cells exhibit an activated phenotype and that TNF-alpha GM-CSF and IL-1 mainly stimulate the differentiation of bone marrow macrophages whereas IFN-gamma activates them. | |
| 7846570 | Postmortem osseous and neuropathologic analysis of the rheumatoid cervical spine. | 1994 Oct 15 | METHODS: Eleven patients with paralysis, secondary to rheumatoid arthritis of the cervical spine were analyzed postmortem. Neurologic classification (Ranawat) included one Class 2, four Class IIIA, and six Class IIIB. Rheumatologic changes included atlantoaxial subluxation, basilar invagination, and subaxial subluxation. During autopsy the entire cervical spine was removed, including the occiput and foramen magnum. The spinal cord and medulla oblongata were removed en toto and examined histologically by a neuropathologist. RESULTS: Nine of the eleven cases revealed abnormal histology of the spinal cord, and in two patients, the spinal cords were normal. Three histologic types of spinal cord compression were identified. In Type 1 (four cases) severe chronic mechanical compression revealed marked mechanical distortion, flattening, and destruction of the cord with secondary Wallerian degeneration of the ascending and descending tracts without anoxicischemic neuron changes. In Type 2 (three cases), there was vascular compression showing ischemic damage to the cord with necrosis of the lateral columns in the ischemic watershed regions supplied by anterior and posterior spinal arteries. In Type 3 (two cases), there was mild mechanical compression showing focal gliosis at the site of compression without ascending or descending tract injury. Two of the eleven cases had thrombosis of the vertebral arteries. Of the eleven cases analyzed, two had normal spinal cords. CONCLUSION: This autopsy analysis of rheumatoid cervical spine suggests that paralysis can be due to both mechanical neural compression and/or vascular impairment. | |
| 1512760 | Asialylated IgG in the serum and synovial fluid of patients with rheumatoid arthritis. | 1992 Jul | A novel enzyme linked immunosorbent assay has been developed that detects an asialylation change in the IgG molecules from patients with rheumatoid arthritis (RA) by the binding of biotinylated RCA 1 (ricin) to capture IgG. Elevated levels of asialylated IgG were detected in paired serum and synovial fluids (SF) of patients with RA. When compared with healthy controls, particularly in the SF (p less than 0.05) correlations of the asialylation change were found in paired samples (p less than 0.01) and between asialylated IgG and rheumatoid factors (p less than 0.01), C-reactive protein (p less than 0.02) and the Lee and Ritchie indices p less than 0.02 and 0.05, respectively. We found the proportion of asialylated IgG was higher in DR4 positive patients, indicating a possible association of these individuals to a sialyl transferase abnormality. | |
| 7688639 | Epitopes on the CB-11 peptide of type II collagen recognized by antibodies from patients w | 1993 Aug | Using the technique of epitope scanning, the binding sites of antibodies to the CB-11 peptide of type II collagen, which is known to induce an inflammatory arthritis in animal models, have been investigated. Sera from seven patients have been tested against 272 peptides representing the CB-11 sequence, each patient produced a different profile of antibody binding and a number of epitopes have been identified. The specific nature of this binding has been established by the reduction in binding by absorption with type II collagen. The reactivity of sera from a further 13 patients, to peptides representing the two most frequently recognized epitopes, has been assessed. | |
| 1555039 | Anti-Proteus antibodies in rheumatoid arthritis same-sexed sibships. | 1992 Apr | One hundred and forty-two RA patients and 121 of their healthy same-sexed siblings were tested for antibodies (Abs) to Proteus mirabilis and Escherichia coli by indirect immunofluorescence. Eighty-five individuals had active RA (CRP greater than 10 mg/l) and 57 inactive RA. The anti-Proteus Ab titre in the active RA group was significantly higher than in the inactive RA and non-RA group (P less than 0.0001 in both cases). Anti-Proteus Abs were significantly elevated in 30 individuals with active RA compared with their healthy HLA-identical same-sexed siblings (P less than 0.001). In 42 HLA-DR4 positive and 15 HLA-DR4 negative active RA patients, the Ab titre was non-significantly higher in the former group. Anti-E. coli Abs were not significantly elevated in any of the groups. Longitudinal data on 36 RA patients demonstrated a significant positive correlation between changes in CRP and changes in anti-Proteus antibody titres (r = 0.52, P less than 0.001). These observations require an explanation. | |
| 8853224 | Effects of desferrioxamine therapy on chronic disease anemia associated with rheumatoid ar | 1996 | OBJECTIVE: To investigate the effects of desferrioxamine (DFO) infusion on chronic disease anemia (CDA) of rheumatoid arthritis (RA) by evaluating interleukin-6 (IL-6) and erythropoietin (EPO) production. PATIENTS AND METHODS: Five patients with RA and CDA (group I) were treated with DFO, 500 mg daily, through a continuous 10-h subcutaneous infusion 5 days a week for 4 weeks. One month after withdrawal, DFO was resumed in all five group I patients (group II) with an increase to 1 g daily following the previous treatment schedule. Clinical and laboratory parameters were evaluated weekly during the two study periods. Serum EPO was measured by radioimmunoassay. IL-6 was detected by the enzyme-linked immunoabsorbent assay method. RESULTS: No significant variations in hematological parameters, IL-6 or EPO levels were observed in group I patients. After 1 week of DFO 1 g daily, reticulocyte counts and EPO improved significantly. Hemoglobin and hematocrit rose significantly after 3 weeks of 1 g daily DFO therapy. Four weeks after DFO withdrawal, EPO, reticulocyte counts, hemoglobin and hematocrit returned to baseline levels. A significant improvement in the clinical parameters of disease activity was observed, particularly in group II patients. CONCLUSION: DFO improves CDA in RA patients. The beneficial effects on erythropoiesis seem to be related to improved EPO responsiveness to the anemia. | |
| 8370165 | Contrasting levels of in vitro cytokine production by rheumatoid synovial tissues demonstr | 1993 Sep | Synovial membrane samples obtained at knee arthroplasty from 22 patients with rheumatoid arthritis (RA) were characterized histologically. Two groups were identified. Tissue samples from 15 patients demonstrated multiple focal lymphoid aggregates of mononuclear cells (group A). Samples from the remaining seven patients demonstrated diffuse mononuclear cell infiltration (group B). Samples of each synovial membrane (0.25 g) were cultured for cytokine production. The highest levels of IL-1 beta and IL-6 were produced by group A tissues: 19.1 +/- 19.6 ng/ml IL-1 beta (mean +/- s.d.) and 264.4 +/- 301.9 ng/ml IL-6, versus 3.8 +/- 6.6 ng/ml and 54.7 +/- 42.6 ng/ml respectively. Small quantities of IL-2 and IL-4 were measured in both groups: the levels of IL-2 in group A cultures were highest (P = 0.04). Moreover, using MoAbs, the most intense cytokine staining in the tissues was detected in group A. Similar total numbers of each cell subpopulation and similar quantities of immunoglobulin and rheumatoid factor synthesis were measured in both groups. It is suggested that the presence of multiple focal lymphoid aggregates associated with higher levels of cytokine production observed in group A represent a greater degree of immunological activation, and may represent a subgroup of patients with a greater potential for articular destruction. | |
| 8250607 | Extra-articular manifestations of rheumatoid arthritis: risk factors for serious gastroint | 1993 Nov | OBJECTIVES: Serious upper gastrointestinal events are an important threat to patients with arthritis who are treated with non-steroidal anti-inflammatory drugs (NSAIDs). In this study risk factors for serious upper gastrointestinal events are identified in patients with possible or definite rheumatoid arthritis (RA). METHODS: A retrospective analysis of factors that might contribute to the risk of serious upper gastrointestinal events was performed in a cohort of 2315 consecutive patients with possible or definite RA. The relative influences of disease severity, drug treatment, particularly with corticosteroids, and history of peptic ulceration were analysed with a conditional logistic regression model for the 106 patients with serious upper gastrointestinal intestinal events and for an equal number of control patients who were matched for age, gender, number of criteria for RA, and disease duration. RESULTS: The incidence rate for serious upper gastrointestinal events was 4.0/1000 patients in each year. The study reconfirmed that age over 60 years, history of peptic ulceration, and use of corticosteroids are risk factors. The presence of extra-articular manifestations of RA was associated with a two to 11-fold increase in the risk for serious upper gastrointestinal events. This risk was independent of the use of corticosteroids. CONCLUSION: Disease severity, in particular the presence of extra-articular features, may be an important factor in the pathogenesis of upper gastrointestinal ulceration in patients with RA who are treated with NSAIDs. | |
| 8064718 | Treatment of patients with refractory rheumatoid arthritis with extracorporeal protein A i | 1994 May | OBJECTIVE: To evaluate the safety and effectiveness of extracorporeal immunoadsorption with protein A (PROSORBA) columns in the treatment of refractory rheumatoid arthritis (RA). METHODS: Eleven patients with refractory RA were enrolled in an open prospective trial of 24 weeks' duration. Nine patients received 15 treatments over a 12-week period, 1 patient received 15 treatments over a 15-week period, and 1 patient received 12 treatments over a 9-week period. RESULTS: Using the composite criteria of Paulus, et al, 9 patients met the > or = 50% criteria when tested at Week 13, while 4 and 2 patients met the > or = 50% and > or = 20% criteria, respectively, when tested at Week 24. In addition, most of the clinical variables in the 9 responders at Week 13 had significantly improved (p < 0.05); 8 of these responders were able to continue for the entire 24-week study without a change in their arthritic medications, and 2 met the American College of Rheumatology criteria for clinical remission at Weeks 12, and 28 and have remained in remission for 6 and 5 months, respectively. Treatment associated side effects were of short duration and resolved without sequela. Four patients became symptomatically anemic during the treatments. CONCLUSION: Our preliminary study suggests that extracorporeal immunoadsorption therapy with protein A columns was well tolerated and may be effective in the treatment of RA. Further expanded and controlled trials are indicated to explore this new therapeutic modality. |