Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 2467351 | Neoantigenic group on Fc fragments in rheumatoid arthritis synovial fluids. | 1988 | Expression of neoantigens during denaturation of IgG by oxygen radicals or proteolysis was assumed to be a possible mechanism for stimulation of rheumatoid factor (RF) formation and/or granulocyte dependent inflammative joint destruction. The so-called human leukocyte elastase (HLE) regularly released by stimulated neutrophils f.e. into the RA synovial fluid is known to split IgG in vitro into papain like fragments and low molecular weight peptides. The n-terminal site of the HLE related Fc is bearing a neoantigenic group which is located near the hinge region but not expressed by the native IgG. The neoantigen itself is represented by the low molecular weight peptides produced by prolonged HLE-IgG proteolysis. Detection of HLE generated Fc in synovial fluids was performed by radioimmunoassay specific for the neoantigen. Patients were divided into the three groups; I RA (n = 23), II inflammative joint effusions except RA (n = 23), III osteoarthritis and trauma (n = 19). The biological effect of the neoantigen on to granulocyte oxidative metabolism was tested by Cytochrome C reduction and chemiluminescence. Neoantigen bearing Fc could be detected in 15 of 23 cases of group I, in group II in 11 of 23 cases and only in 7 of 19 cases in group III. The median concentrations were 0.62 micrograms in group I and zero in II and III. The HLE derived Fc were able to inhibit the oxidative metabolism of activated granulocytes in vitro. The O2- production of stimulated granulocytes was depressed dose dependent by the neoantigen. The neoantigenic group itself does not react with RF as proved by nephelometric titration of HLE derived Fc, neoantigenic peptide and native IgG against a RF standard. | |
| 2026869 | Cytokines in chronic inflammatory arthritis. VI. Analysis of the synovial cells involved i | 1991 May 15 | Granulocyte-macrophage CSF (GM-CSF) is a potent stimulator of macrophages and neutrophils and is produced by rheumatoid arthritis (RA) synovium. We now report studies that identify some of the synovial cells and cytokines responsible for local GM-CSF production and gene expression in RA. GM-CSF was assayed by ELISA in supernatants from cultured RA fibroblast-like synoviocytes stimulated with various cytokines (IL-1 beta, TNF-alpha, macrophage-CSF, IFN-gamma, IL-6, and TGF-beta). Immunoreactive GM-CSF was detected in IL-1 beta and TNF-alpha-stimulated cultures, but not in cells cultured in medium or stimulated with any of the other cytokines. IL-1 and TNF-alpha had a synergistic effect on GM-CSF production. GM-CSF gene expression by fibroblast-like synoviocytes was analyzed by ribonuclease protection assay, Northern blot analysis, and in situ hybridization. Both IL-1 beta and TNF-alpha induced GM-CSF mRNA accumulation, with a maximum effect after 4 h of stimulation. We then studied GM-CSF production by macrophage-like synoviocytes (MLS) isolated from fresh synovial specimens by flow microfluorimetry. Fresh MLS spontaneously secreted the cytokine and exogenous IL-1 beta or TNF-alpha had no effect. After 1 wk in culture, additional stimulation with IL-1 beta or TNF-alpha was required for GM-CSF production. Finally, in situ hybridization performed on freshly isolated subpopulations of synovial cells, identified GM-CSF RNA transcripts in MLS. | |
| 3392446 | [Osteoporotic changes in rheumatoid arthritis--longitudinal bone mass study and effect of | 1988 Mar | Serial measurements of bone mass were carried out by single photon absorptiometry and/or X-ray microdensitometry of the second metacarpus in 29 rheumatoid arthritis patients not treated by corticosteroids. The effect of 1 alpha-hydroxyvitamin D3 on rheumatoid arthritis was also investigated by longitudinal bone mass study. In premenopausal females and also males, the rate of radial diaphyseal bone loss was less than 1%/year and bone loss was seen only in the periarticular region of affected joints. On the other hand, bone loss was much more rapid in both the periarticular and diaphyseal regions in postmenopausal patients. 1 alpha-hydroxyvitamin D3 administration for more than 1 year produced no significant change of blood biochemical examination and Lansbury's index, but resulted in a significant attenuation of bone loss rate. | |
| 1995763 | Serum erythropoietin levels in the anaemia of chronic disorders. | 1991 Jan | Serum erythropoietin (S-EPO) levels were measured in 50 patients with anaemia of chronic disorders (ACD), classified into three groups according to their aetiology: inflammatory (n = 20), infectious (n = 15) and neoplastic (n = 15). The inflammatory group showed a higher mean S-EPO level (mean value +/- SEM, 69 +/- 11 mU ml-1) than the neoplastic (43 +/- 5 mU ml-1; P less than 0.05) and infectious groups (27 +/- 4 mU ml-1; P less than 0.01). The S-EPO level in the inflammatory group also differed from that of 32 healthy controls (36 +/- 3 mU ml-1; P less than 0.05). Fourteen patients with added iron deficiency (12 subjects from the inflammatory group) showed the highest S-EPO concentration (72 +/- 17 mU ml-1). Conversely, S-EPO levels were lower in febrile subjects (12 patients with infection and five with malignancy) than in non-febrile patients (28 +/- 4 mU ml-1 vs. 55 +/- 7 mU ml-1; P less than 0.01). In the infectious group, the logarithm of S-EPO correlated directly with the haemoglobin and haematocrit values. We conclude that differences in S-EPO concentration in ACD may be further related to the patient's iron stores and temperature. A decrease in EPO production may contribute to the pathogenesis of ACD secondary to infection. | |
| 2495010 | Interleukin-1 induces interleukin-1 alpha and interleukin-1 beta gene expression in synovi | 1989 Mar | Cellular interactions involved in the chronic inflammatory response, characteristic of those found in the joints of rheumatoid arthritis patients, were investigated by examining the effect of interleukin-1 (IL-1), tumor necrosis factor alpha, and gamma-interferon on the regulation of IL-1 gene expression and production by synovial fibroblasts. Biologically active IL-1 was detected in lysates of IL-1-treated rat and human fibroblasts that had been isolated from synovial tissue by collagenase digestion. Northern blot analysis of RNA isolated from these cells revealed the expression of IL-1 alpha and IL-1 beta transcripts. Neither the IL-1 transcripts nor the biologic activity of IL-1 was found in untreated synovial fibroblasts. The messenger RNA induction in synovial cells was followed by a time- and dose-dependent expression of intracellular IL-1 activity. Human monocytes and human skin fibroblasts also responded to IL-1 treatment by producing IL-1-specific transcripts. These observations suggest that IL-1 plays a key role in stimulating immune and inflammatory responses and in sustaining those responses through continued production at sites of inflammation. | |
| 2789256 | IL-6/IFN-beta 2 in synovial effusions of patients with rheumatoid arthritis and other arth | 1989 Oct 1 | We have looked for IL-6, a cytokine that has immunomodulating and inflammation-associated activities, in joint exudates (fluid and mononuclear cells) from patients with rheumatoid arthritis and other arthritides using both biologic and biochemical assays. IL-6 was assessed by its ability to stimulate alpha 1-antichymotrypsin secretion from the human hepatoma cell line Hep3B clone 2, an activity which is blocked by an antiserum to Escherichia coli derived IL-6, and by the growth of the IL-6-dependent murine hybridoma 7TD1 cell line. IL-6 isoforms in synovial fluid were characterized by immunoaffinity chromatography followed by Western blotting. The presence of IL-1 in synovial fluids and its production by synovial fluid mononuclear cells was monitored by Western blotting and indirect immunofluorescence with polyclonal anti-IL-1 beta antisera. In an analysis of 30 effusions from 27 rheumatoid patients with acutely inflamed joints, abundant quantities of IL-6 (greater than 2 ng/ml) were detected in 23 by the alpha 1-antichymotrypsin bioassay. Several rheumatoid synovial fluids also had elevated IL-6 levels in the 7TD1 bioassay. Seven of nine nonrheumatoid effusions also contained high levels of IL-6 (greater than 2 ng/ml). No IL-1 (less than 0.25 ng/ml) could be detected by Western blotting in 10 rheumatoid effusions even though eight of these contained high levels of IL-6. The IL-6 activity could be neutralized with a rabbit antiserum to rIL-6. Multiple IL-6 isoforms (25, 30, 45 kDa) were present in two rheumatoid and one traumatic effusion studied. Fresh mononuclear cells isolated from various synovial effusions did not appear to make IL-6 constitutively, as no IL-6 could be detected in the media of cells cultured for 12 to 18 h after isolation. Similarly, there was no constitutive production of IL-1 by these cells. However, synovial fluid mononuclear cells could be induced to secrete both IL-6 and IL-1 after stimulation with LPS. The LPS-responsive cells were monocytes and not lymphocytes or dendritic cells. These findings suggest that IL-6 is involved in inflammatory joint disease. However, the primary cells synthesizing it may be located in the synovial lining instead of the joint exudate. | |
| 2091373 | Neutrophil, monocyte and lymphocyte locomotion in rheumatic fever and rheumatoid arthritis | 1990 Apr | Neutrophil, monocyte and lymphocyte chemotaxis was investigated in 19 patients with active rheumatic fever (10 with carditis), in 15 patients with rheumatoid arthritis and in 20 healthy, age-matched controls. Chemotaxis assays were repeated in the rheumatic fever patients on the fifth day of therapy and two weeks after remission. Neutrophil and monocyte chemotaxis was found to be significantly decreased in the rheumatoid arthritis patients when compared with the controls and rheumatic fever patients. In contrast, neutrophil chemotactic activity was significantly higher in the rheumatic fever patients when compared with the healthy controls. Monocyte and lymphocyte chemotaxis in patients with rheumatic fever was not significantly different when compared with the controls. Neutrophil, monocyte and lymphocyte locomotion was found to be significantly decreased on the fifth day of salicylic acid or prednisolone treatment. | |
| 3711609 | Wrist arthrodesis. | 1986 May | Twenty consecutive patients were treated with wrist arthrodesis. Nine patients had rheumatoid arthritis, and eleven patients had a variety of other arthritic conditions. The average follow-up time was 34 months. Clinical examination and roentgenograms showed that eighteen patients had solid fusion of their wrists, with an average of 11 weeks of immobilization. Two patients had delayed union--one of them removed his cast after the operation. No reason for the delayed union was found in the second patient, who had rheumatoid disease. Ultimately, both patients had solid fusions after a total immobilization time of 20 weeks and 16 weeks, respectively. Solid fusion, pain relief, and satisfactory functional results can be achieved following wrist arthrodesis. Prerequisites for obtaining such results are as follows: First preoperative assessment of the patient's upper extremity level of function and range of motion (ROM) of all other joints of the extremity, and radiographic assessment of wrist and hand deformities. Second, during surgery, rigid fixation should be obtained and wrist deformity if present, as in rheumatoid disease, should be corrected. Third, a postoperative rehabilitation program should include range of motion of other joints, muscle strengthening, and functional activities. | |
| 3203189 | Detection of suspected inflammatory joint disease with a new simple self-administered hand | 1988 Dec | A self-administered hand test was used to screen 5262 persons aged 40-70 living in a rural district in southern Sweden. It revealed evidence of hand impairment in 13%. The prevalence of RA was 1.1%. At the screening procedure a subgroup of 48 previously unrecognized individuals with inflammatory joint disease was identified. They were assessed by a rheumatologist, who established the following diagnoses: four definite RA, eight probable RA, three psoriatic arthritis, one unclassifiable arthritis, 10 osteoarthritis and 22 non-specific arthralgia. No advanced RA was detected. Two were seropositive and another was erosive. One with RA, one with psoriatic arthritis and three with arthralgic symptoms were unable to work. Most had only a minor need for further medical aid. The test was thus able to identify persons with hand impairment. Follow-up studies will address the practical implications of the screening procedure. | |
| 2143713 | [Evaluation of tolerability and efficacy of a nabumetone preparation in the treatment of p | 1990 Jun 15 | In an open uncontrolled trial 30 patients (4 males, 26 females) aged 43-70 years suffering from active rheumatoid arthritis (diagnosis based on American Rheumatoid Association criteria) were treated with nabumetone (one 1 g capsule daily per os). Symptoms were evaluated according to subjective and objective parameters (spontaneous resting pain, night pain, pain during movement. Huskinsson's visual analogic scale, Ritchie's articular index, hand grip, duration of morning stiffness; number of joints involved, global function capacity, Lee index); an overall improvement was observed. In view of the prevalence of positive judgements, nabumetone may be considered a valid resource for symptomatic management of active rheumatoid arthritis. Treatment had to be withdrawn in four cases: for gastrointestinal side effects in 3 cases, slight erythema in one case, often accompanied by increasing severity of the painful symptoms. Tolerability both general and local was considered good. | |
| 2104218 | Autocrine regulation of rheumatoid arthritis synovial cell growth in vitro. | 1990 Mar | Rheumatoid arthritis (RA), and not osteoarthritis (OA) synovial cells proliferate in serum-free medium, a finding that suggests that, in vitro, RA synovial cells may be stimulated to grow by the continuous autocrine production of at least one polypeptide growth factor. Adding monoclonal antibody 1D11.16, or rabbit polyclonal anti-tumor growth factor beta (anti-TGF-beta) antibodies (both neutralizing antibodies to TGF-beta 1 and TGF-beta 2) to RA synovial cells, in culture, caused a significant reduction in cell growth, an effect not seen when other growth factor antibodies (platelet-derived growth factor [PDGF], epidermal growth factor [EGF], or EGF receptor) were added to the culture medium. Taken together, these data are consistent with the concept that RA synovial cell growth in vitro is driven endogenous TGF-beta. Moreover, when EGF was added to the culture medium, this caused the numbers of RA, and not OA, synovial cells to increase significantly. This finding suggests that RA synovial cells are in G1 phase of the cell cycle; an effect that could be mediated by endogenous TGF-beta. | |
| 2377807 | [Monoclonal gammopathy of uncertain significance in rheumatic disease]. | 1990 May | Among 358 patients with rheumatic diseases, the incidence of monoclonal gammopathy of undetermined significance (MGUS) as detected by immunofixation was 4.4% (11 of 248 patients) in rheumatoid arthritis (RA), 3% (1 of 32 patients) in systemic lupus erythematosus (SLE), 6% (3 of 49 patients) in Sjögren's syndrome (SS) and 3% (1 of 29 patients) in progressive systemic sclerosis (PSS). Solid tumor was present in 4 (36%) of the 11 RA-MGUS patients. In these cases the monoclonal component could be related to a paraneoplastic syndrome rather than to rheumatic diseases. The association of rheumatic diseases, MGUS, solid tumor and immunological disorders are discussed. | |
| 1971754 | Polymorphisms in the VK gene patterns of rheumatoid arthritis patients and control individ | 1990 | Restriction nuclease digests of DNAs from rheumatoid arthritis patients and control persons were studied by blot hybridization using immunoglobulin VK gene probes of subgroups I-III. Two restriction fragment length polymorphisms (RFLP) were detected in Bg1II digests with a VKI gene probe. One of the RFLPs is linked to rheumatoid arthritis with a relative risk of 5 (p less than 0.01). The observation may be of pathogenetic interest. | |
| 3407454 | Stabilization of the unstable upper cervical spine in rheumatoid arthritis. | 1988 | We present our clinical experience and the results of surgical treatment of 13 patients with rheumatoid involvement of the cervical spine, namely severe atlanto-axial dislocation. A posterior fusion was carried out using a bicortical H-shaped iliac crest bone graft and steel wire. Postoperatively all patients were immobilized for 8 weeks in a Halo cast. There were no postoperative complications and all patients showed a stable fusion confirmed by radiography. Complete pain relief was obtained in 9 patients, partial in 4. | |
| 2567539 | Definition of DRw10 by restriction fragment length polymorphism. | 1989 Apr | To better define the presence of the DRw10 haplotype which has sometimes proved difficult to type by using serologic reagents, Southern blot analysis was performed on seven DRw10 heterozygous individuals with rheumatoid arthritis. Using the restriction enzymes Taq I or BamH I, the restriction fragment length polymorphism (RFLP) pattern for the DRw10 haplotype was clearly distinguishable from that of other DR alleles. Digestion with Taq I revealed a unique DR beta/Taq I 12.20 fragment. A characteristic DR beta/Taq I 4.60 fragment was also present only in DRw10 and DR1 haplotypes. Digestion with the restriction enzyme BamH I revealed a DR beta/BamH I 5.07 fragment also present in DRw10 and DR1 haplotypes, and a DR beta/BamH I 4.30 fragment shared with the DRw52 and DR2 haplotypes but not found in DR1 haplotypes. The pattern was readily distinguished from those given by the haplotypes DR4, 7 and w9. Family studies of five individuals demonstrated appropriate segregation of the restriction fragments. In particular, segregation of DRw10 haplotypes from DR1 haplotypes was clearly shown in a family in which the DRw10 haplotype was associated with rheumatoid arthritis in two individuals. Southern blot analysis proved to be a useful alternative method for identifying the DRw10 allele in certain combinations where this allele has been difficult to define serologically. | |
| 3510685 | Clinical advantages from measurement of IgM-rheumatoid factor by enzyme immunoassay. | 1986 Feb | Two enzyme immunoassays for rheumatoid factor (RF) were compared with the traditional latex agglutination test. Preference is expressed for an ELISA specific for IgM-RF because it yields specific, quantitative results. Variability of this assay was least in sera containing moderate levels of RF and it was less precise at low concentrations. Survey of a random selection from the local population showed a similar prevalence of IgM-RF positivity as revealed by previous surveys using agglutination techniques. We conclude that measurement by ELISA yields no great increase in the discriminative ability of RF testing. | |
| 3298296 | Health status and utility measurement viewed from the right brain: experience from the rhe | 1987 | Questionnaires for measuring function, health status, and quality of life have been developed for the rheumatic and musculoskeletal disorders. These new measures are as valid and as reliable as traditional measures of clinical status in clinical trials and health services research and add a valuable dimension to outcome assessment. However, they have limitations for use in patient care. Questionnaires cannot determine the etiologic basis of functional disability; nor cover any one function in enough depth; nor deal with the relative nature of function; nor account for the differences in functional priorities. Questionnaires are statistical approaches and based on normative model; patient care is humanistic emphasizing differences. Nevertheless, the interaction between psychometric approaches and concerns of patient care is a necessary and desirable goal for all we seek to accomplish with clinical investigation. | |
| 3066330 | Immunophotometric quantification of extravascular immunoglobulin deposits in the synovial | 1988 | The amount of extravascular immunoglobulin deposits in the synovial membrane of patients with osteoarthritis and rheumatoid arthritis was studied in comparison with that of patients suffering from non-joint diseases. Immunoglobulin deposits were immunostained using the three-layer immunoperoxidase method. The staining results were quantified with the help of a microscope photometer connected with a scanning stage. Several experiments involving artificial test substrates, diseases with allegedly increased extravascular deposits or diseases not exhibiting extravascular deposits of immunoglobulins are used to validate the described microspectrophotometrical approach for measuring extravascular immunoglobulin deposits. The scanning photometry demonstrates significantly higher amount of extravascular immunoglobulin deposits in rheumatoid arthritis as compared with osteoarthritis and non-joint diseases. | |
| 2877852 | Comparison of white blood cell dyscrasias during sulphasalazine therapy of rheumatoid arth | 1986 | A total of 7 out of 158 rheumatoid arthritis patients followed for 6 months have developed leucopenia during sulphasalazine therapy at our centre. Two of these patients developed profound leucopenia which necessitated admission to a laminar flow unit, and case reports of these are documented in detail. These results are compared with those from other centres in the United Kingdom where patients with rheumatoid arthritis have been treated, and also with experience gained from patients with inflammatory bowel disease who have been treated with sulphasalazine. | |
| 2964958 | A cellular deficiency in the rheumatoid one-way mixed lymphocyte reaction. | 1988 Jan | Activated lymphocytes expressing transferrin receptors (TFR) are present in the peripheral blood in rheumatoid arthritis. Characterization of these cells shows a CD4 dominance with depressed expression of CD8 and NK antigens, similar to synovial infiltrates. In the present study, one-way mixed lymphocyte reactions were performed to compare the response of rheumatoid patients with that of normal individuals. The TFR+ cells generated were characterized by double-label immunofluorescence. The TFR+ cells from rheumatoid responders showed elevated CD4+ cells and depressed CD8 and Leu-7 (NK) expression compared with normal, throughout the response. This defect was corrected by adding recombinant interleukin 2 at the beginning of the culture period. CD8+ cells stimulated to express TFR following interleukin 2 supplementation of the rheumatoid responses co-expressed HLA-DR. Functional studies indicated that TFR+ CD8+ cells were not cytotoxic, indirectly suggesting them to be suppressor cells. These findings indicate that significant immunoregulatory abnormalities in rheumatoid arthritis may reflect abnormal interleukin 2 biology. |