Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
ID | PMID | Title | PublicationDate | abstract |
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7569462 | [Treatment with cyclosporine of refractory rheumatoid arthritis]. | 1995 Feb | Cyclosporine may be useful in the treatment of rheumatoid arthritis refractory to other immunosuppressive agents, in doses of less than 10 mg/kg/day to minimize its nephrotoxic potential, that is enhanced with prolonged use or concomitant administration of anti-inflammatory drugs. We report 15 patients aged 50 +/- 12 years with erosive rheumatoid arthritis lasting 5 +/- 4 years and refractory to other immunosuppressive agents. They were studied during one year and received cyclosporine in initial doses of 2.5 mg/kg/day that were increased to 5 mg/kg/day, assessing clinical response, blood pressure and serum creatinine. Nine patients, that received a maximal dose of 3.4 +/- 0.7 mg/kg/day during 7 +/- 4 months, improved; a 30% increase in creatinine was observed in 3, blood pressure raised in six and two had hepatic toxicity. In the six patients that did not improve, the mean treatment lapse was 4 +/- 3 months and the maximal dose achieved was 2.7 mg/kg/day; creatinine increased in one and blood pressure increased in 4. It is concluded that although the clinical response to cyclosporine was good, only 4 patients completed one year of treatment, due to the frequent secondary effects of the drug. | |
8297525 | Cellular immune mechanisms in rheumatoid arthritis and other inflammatory arthritides. | 1993 Dec | Advances in molecular genetics, cellular immunology and microbiology have offered promise in unravelling the aetiopathogenesis of inflammatory arthritides such as rheumatoid arthritis and reactive arthritis. Such insights are challenging the orthodox view that these diseases are primarily autoimmune in nature, and should lead to exciting and novel therapeutic approaches. | |
1295235 | [The role of antiglobulin antibodies in pathophysiology of various internal diseases]. | 1992 Jan | Antiglobulins are a heterogenous group of antibodies specific for a large number of antigenic determinants on the heavy chains of various classes and on light chains. They are capable of reacting with hidden antigenic determinants of gamma globulins after they have been exposed by the action of proteolytic enzymes or after antigen-antibody reaction during which changes occur in the spatial configuration of the Fc fragments of immunoglobulin causing that they assume immunogenic properties. Antiglobulin antibodies against episomes in the Pab fragment of other antibodies have a strong regulatory influence on the immune response in view of their ability of specific interference with the response to a specific antigen. Antiglobulin antibodies may exert a protective effect but also a pathogenic effect. The latter has been demonstrated in atopic diseases, in IgA glomerulonephritis, in rheumatoid arthritis, in infectious mononucleosis, cryoglobulinaemia, in patients with IgA deficiency associated with presence of antiglobulin antibodies to IgA after transfusion of plasma or intravenous infusion of gamma globulins containing IgA. | |
7559823 | Extensor tendon ruptures in rheumatoid arthritis. | 1995 Aug | The best treatment for extensor tendon rupture is prevention, either by medical management or surgical tenosynovectomy before tendon ruptures occur. Once a rupture has occurred, tendon transfer or free tendon grafting can provide acceptable restoration of extensor function. Communication with the rheumatologist is necessary to provide timely treatment for chronic dorsal tenosynovitis (and impending tendon rupture) or for single finger extension loss before the disease progresses to multiple finger extension loss. Consideration always must be given to associated joint involvement when planning surgical treatment. | |
1480243 | [Arthroscopic ankle arthrodesis: a new technique]. | 1992 Dec 26 | We report on 5 patients who successfully underwent an arthroscopic ankle arthrodesis in the department of Orthopaedics of the University Hospital in Nijmegen. Three patients had haemophilia, one rheumatoid arthritis, and one arthrosis following trauma. The results were satisfactory. The patients had surprisingly little postoperative pain. It appears from the literature that regarding morbidity in terms of infection, pseudarthrosis and consolidation time, arthroscopic arthrodesis compares favourable with the open procedures. | |
8614858 | Ultrasonographic imaging of the hand and wrist in rheumatoid arthritis. | 1995 Nov | OBJECTIVE: To assess ultrasound findings in patients with rheumatoid arthritis affecting the hand and wrist compared to normal volunteers. DESIGN: Metacarpophalangeal and carpal articulations were imaged ultrasonically. Two readers reviewed static images for synovial, cartilaginous, and bony abnormalities using severity and probability scales. Ultrasound findings were correlated with disease activity. PATIENTS: Ten normal volunteers and 29 patients with known rheumatoid arthritis. RESULTS: Synovial abnormalities and erosions were most commonly identified in the rheumatoid hand and wrist (p < 0.01). Criteria used for normal and abnormal cartilage did not predict normal and disease states. Significant differences in synovial abnormalities and erosions were observed between the inactive and mildly active disease groups as well as the active and mildly active disease groups (p < 0.01). CONCLUSION: Ultrasound can detect abnormalities of the hand and wrist in patients with rheumatoid arthritis compared to normal volunteers. Normal articular anatomy is well demonstrated ultrasonically. | |
8239648 | Alterations in the carbohydrate structures of an abnormal protein from sera of patients wi | 1993 Nov 15 | G4-11, an abnormal immunoglobulin G4 (IgG4) glycoprotein, highly purified from the sera of patients with rheumatoid arthritis and from healthy individuals, contains two asparagine-linked sugar chains in one molecule. Comparative studies of the sugar chains released by hydrazinolysis revealed that the structures of the sugar chains of rheumatoid arthritis G4-11 are quite different from those of normal individuals. Although all G4-11 contained biantennary complex-type oligosaccharides like in the case of serum IgGs, samples from patients with rheumatoid arthritis had less galactosylated forms than those from normal individuals. These results indicated that this galactose deficiency of the sugar chains occurs in the abnormal IgG4 molecule of rheumatoid arthritis patients, just as was found in whole serum IgG. | |
7911453 | Production of soluble ICAM-1 by mononuclear cells from patients with rheumatoid arthritis | 1994 Feb | The present study was designed to quantify the level of the soluble form of ICAM-1 (sICAM-1) produced by mononuclear cells (MNC) of rheumatoid arthritis (RA) patients, and to correlate these levels with the disease activity and with the amounts of cytokines or rheumatoid factors (RF) produced by MNC. Unstimulated synovial fluid (SF) MNC produced higher amounts of sICAM-1 than peripheral blood (PB) MNC in RA patients (P < 0.01). sICAM-1 production by PHA-stimulated MNC was higher in RA SF MNC than RA or normal PB MNC (P < 0.01). The amounts of SICAM-1 produced correlated with the amounts of soluble IL-2 receptor produced (P < 0.02) but not with IL-1B or the Lansbury activity index in RA PB MNC. sICAM-1 correlated with the amounts of soluble CD23 and IL-4 produced by normal PB MNC (P < 0.01). The amounts of sICAM-1 correlated with IgG-RF (P < 0.02) and IgM-RF (P < 0.01) produced by unstimulated MNC obtained from the bone marrow (BM) of RA patients. ICAM-1 expression of T-lymphocyte subsets, B lymphocytes, and monocytes obtained from RA PB and RA BM assayed by two-color flow cytometry ranged from 0.1 to 6%, which was not appreciably different from that of normal controls. The monocyte fraction of RA PB MNC produced significantly higher amounts of sICAM-1 than lymphocyte fraction. These results suggest that sICAM-1 produced by MNC may be a marker of cell activation in T and B lymphocytes, in contrast to the transient increase of ICAM-1 expression. | |
8496854 | Human monoclonal rheumatoid factor derived from rheumatoid synovial cells monospecific for | 1993 Apr | Rheumatoid factors (RF) in rheumatoid arthritis (RA) are polyclonal autoantibodies directed against antigenic epitopes located in the Fc portion of the IgG molecule. Hybridoma technology has overcome the difficulty of their polyclonality, so that monoclonal RF (mRF) can be examined for their individual binding specificities and genetics. We isolated a monoclonal IgM RF secreting hybridoma (designated H4) from the rheumatoid synovial cells (RSC) of a patient with RA. H4 bound specifically with rabbit IgG (RIgG) and had no human IgG (HIgG) reactivity. By direct binding ELISA and absorption experiments, 6% of the RIgG reactive RSC RF in this patient with RA was monospecific for RIgG. H4 was tested against RIgG F(ab')2 and pFc' fragments, and bound only to the pFc' fragment (CH3 domain). Moreover, H4 mRF had high avidity for RIgG in a capture ELISA. Total RNA was extracted and the variable region heavy (VH) and light (VL) chain cDNA were amplified using polymerase chain reaction technology. Sequence analysis of the IgM RF VH and VL chain genes indicated usage of the VH26 germline gene (VhIII gene family) and a new V lambda germline gene. Our results suggest preferential use of restricted germline genes in the formation of autoantibodies in human autoimmune diseases. The pathological significance of RIgG specific RF is still unclear. However, this finding suggests that all RSC RF production may not necessarily be induced by autologous IgG. | |
7640371 | Histopathological and histoenzimological investigations of the rheumatoid articular cartil | 1994 Jan | Twenty seven biopsies of articular cartilage taken intraoperatively from patients with Rheumatoid arthritis (RA) and from control patients with traumas were examined using histopathological techniques (HE, VG, PAS-Alcian, Gömöri, Safranine 0) and histoenzymological techniques (Acid phosphatase-lysomal marker, Chondroitinsulphatase, Peroxidase). Histopathologically, the rheumatoid articular cartilage appears with superficial and deep cartilaginous fissures, frequent perichondrocytic gaps associated with modification of the tinctorial activity. At the pannus synovia-cartilage junction we found invasive and destructive synovial inflammatory infiltrates penetrating and eroding the cartilage. Histoenzymologically, the rheumatoid chondrocytes have a high lysosomal potential (phosphatasic, chondroitinsulphatasic) and highly oxidative potential (peroxidasic) specific for lesion modifications. | |
1732316 | Linear IgA bullous dermatosis associated with rheumatoid arthritis. | 1992 Jan | A case of linear IgA bullous dermatosis associated with rheumatoid arthritis is described. The eruption consisted of multiple irregular erythematous plaques and small numbers of tense vesicles mainly on the trunk. An immunofluorescence study showed linear IgA and IgG deposition along the basement membrane zone, whereas C3 deposition was not found. IgA or IgG anti-basement membrane zone antibody was not detected in the serum. Treatment with dapsone resulted in good control of the eruption. Coexistence of linear IgA bullous dermatosis and rheumatoid arthritis has not been reported previously. | |
8136803 | [Anti-inflammatory properties of interleukin-4]. | 1993 Feb | Interleukin 4 (IL4) is a cytokine produced by T cells and mast cells/basophils. IL4 has a key role in IgE production and in the pathogenesis of atopic diseases. Disorders such as rheumatoid arthritis are characterized by increased production of proinflammatory cytokines and reduced production of IL4. Furthermore, rheumatoid T cells are of the TH 1 type, not producing IL4. In contrast, circulating IL4 has been detected in scleroderma patients, whose T cells are of the TH 2 type, producing IL4. Since IL4 inhibits the production of proinflammatory cytokines such as IL1, IL6, TNF alpha and IL8, we hypothesized that a deficit in IL4 production might be related to the pathogenesis of rheumatoid arthritis. Addition of IL4 strongly reduced the production of proinflammatory cytokines and expression of corresponding mRNA by synovial membrane pieces from RA patients. RA synovitis is also associated with marked proliferation of synoviocytes. Studies of synoviocytes showed that IL4 inhibited the growth promoting effect of PDGF and IL1 beta. IL4 also inhibited production of IL6 by juxta-articular bone pieces. IL4 was found to reduce disease activity and progression in various arthritis models. These anti-inflammatory and anti-proliferative properties suggest that IL4 may be of potential clinical value in RA. Conversely, as IL4 induces dermal fibroblasts to secrete collagen, IL4 might be involved in the pathogenesis of scleroderma. | |
1378777 | Molecular basis for the association between HLA DR4 and rheumatoid arthritis. From the sha | 1992 Jun | Susceptibility to rheumatoid arthritis (RA) maps to residues QKRAA/QRRAA in the third hypervariable region of the HLA DR beta 1 chain. Peptides from the same area of MHC class II molecules are able to modulate the T-cell repertoire by deleting self-reactive T-cells. The Epstein Barr virus glycoprotein gp110 and the dna J heat-shock protein from E. coli mimic the third hypervariable region of HLA-Dw4DR beta 1. Thus, the same area of HLA DR beta 1 carries susceptibility to RA, modulates the T-cell repertoire and is mimicked by human pathogens. RA may originate from a particular shape imposed on the T-cell repertoire by the QKRAA/QRRAA sequence in the third hypervariable region of HLA DR beta 1. | |
8185691 | Synovial interleukin-1 receptor antagonist and interleukin-1 balance in rheumatoid arthrit | 1994 May | OBJECTIVE: To quantify interleukin-1 receptor antagonist (IL-1ra) and IL-1 production and gene expression by rheumatoid arthritis (RA) synovial tissue (ST) cells. METHODS: IL-1 alpha, IL-1 beta, and IL-1ra protein levels were measured by enzyme-linked immunosorbent assay in fresh and cultured ST cells, purified synovial macrophages, and fibroblast-like synoviocytes (FLS). The relative expression of the secreted form of IL-1ra (sIL-1ra) and the alternatively spliced intracellular form (icIL-1ra) was determined by reverse transcription polymerase chain reaction (RT-PCR) techniques. RESULTS: IL-1 alpha, IL-1 beta, and IL-1ra were present in fresh and cultured ST cell samples of synovium from RA and osteoarthritis patients. IL-1ra:IL-1 ratios ranged from 1.2 to 3.6, which is below the 10-100-fold excess of IL-1ra needed to inhibit IL-1 bioactivity. Isolated CD14+ synovial macrophages secreted IL-1ra, but the amount was much less than that of alveolar or in vitro-derived macrophages. Cultured FLS contained intracellular IL-1ra but secreted little IL-1ra into the culture supernatants. RT-PCR showed that icIL-1ra mRNA was more abundant than sIL-1ra mRNA in FLS and unfractionated ST cells. CONCLUSION: IL-1ra production by RA ST cells is deficient relative to total production of IL-1. | |
8596163 | Treatment of progressive rheumatoid interstitial lung disease with cyclosporine. | 1995 Nov | A 62-year-old man with longstanding rheumatoid arthritis (RA) presented with dyspnea. Active rheumatoid interstitial lung disease was documented by high resolution computed tomography, gallium scan, and bronchoalveolar lavage. He responded to high dose prednisone, but had unacceptable side effects. Chlorambucil and cyclophosphamide were not steroid sparing. After starting cyclosporine 3 mg/kg/day he was able to stop prednisone and his symptoms improved and stabilized. Pulmonary function showed sustained improvement during 2 years of followup. His RA has been well controlled. Side effects have been mild hypertension and increased serum creatinine. | |
7599511 | Effects of zinc supplementation on the phagocytic functions of polymorphonuclears in patie | 1994 Dec | The phagocytosis of blood polymorphonuclear cells (PMNs) was measured by cytofluorometry in 22 patients with inflammatory rheumatic diseases before and after a 60-day treatment with 45 mg zinc daily or a placebo, and the values were compared with those obtained in a group of healthy subjects. Plasma zinc was lower than controls before supplementation and phagocytosis assessed by the percentage of PMNs exhibiting phagocytic activity was significantly impaired. Zinc supplementation increased the percentage of phagocytic PMNs and the mean phagocytic activity, particularly in subjects with initial low phagocytosis. The impairment of PMN phagocytosis could therefore be corrected by zinc supplementation, but the clinical consequence of this stimulant effect remains unknown. | |
1308968 | [Immunosuppressive therapy of secondary amyloidosis associated with rheumatoid arthritis o | 1992 Dec | Ten cases of renal amyloidosis associated with rheumatoid arthritis (n = 9) or Still's disease (n = 1) were studied retrospectively. One patient had end-stage renal failure at first presentation, whereas the nine others had nephrotic syndrome without renal failure as the initial manifestation of amyloidosis. In the three untreated patients, renal function deteriorated steadily and dialysis was rapidly necessary. In contrast, among the six patients given chemotherapy, four had normal renal function under therapy. These favorable therapeutic results are analyzed and compared with previously published data on the treatment of secondary amyloidosis. | |
8922170 | The management of rheumatoid nodules. | 1996 Oct | Rheumatoid nodules are present in approximately 25% of patients with seropositive rheumatoid arthritis (RA) and are the most common extra-articular lesions of this disease. Current methods of treatment include a variety of antirheumatic agents, surgical excision, or observation. Treatment options for the rheumatoid nodule are limited, due in part to the highly variable nature of the nodule. This series describes 4 seropositive RA patients, all with extensive rheumatoid nodules. Three were successfully treated by surgical excision, and 1 was successfully treated with conservative management. Surgical treatment is effective. Indications include local pain, nerve compression, limited range of motion, erosion, and infection. | |
1616322 | Controlled trial of methotrexate versus 10-deazaaminopterin in the treatment of rheumatoid | 1992 May | A 15 week double blind controlled trial of methotrexate and 10-deazaaminopterin for the treatment of rheumatoid arthritis (RA) was performed in 26 patients. Significant improvement in all measured clinical parameters was observed in the two patient groups. The drugs were well tolerated; only one patient (10-deazaaminopterin) withdrew from the study because of side effects. It is concluded that, in the context of this relatively short clinical trial, 10-deazaaminopterin is at least as beneficial as methotrexate in the treatment of RA. | |
8575138 | Gliadin immune reactivity in patients with rheumatoid arthritis. | 1995 Sep | OBJECTIVE: To investigate whether patients with rheumatoid arthritis (RA) have immunological or clinical evidence of gluten hypersensitivity. METHODS: Antigliadin antibodies (AGA) and antireticulin antibodies (ARA) were determined in two groups of RA patients and in a control group of patients with spondylarthropathies. In the first group of 42 patients with recent-onset RA, AGA and ARA were studied longitudinally during a one-year follow up period. In the second group of 36 patients with advanced RA and various abdominal symptoms examined by upper gastrointestinal endoscopy, AGA and ARA were determined cross-sectionally. RESULTS: Increased AGA (IgA or IgG) levels were found in 37% (29/78) of all RA patients compared to 12% (3/25) of controls. ARA positivity (IgG) was found in 4% (3/78) of RA patients and in none of the controls. AGA positivity was increased in patients with early RA compared to patients with advanced disease (48% vs. 25%) but the difference was not statistically significant. However, no true gluten hypersensitivity with positive AGA and ARA together with villous atrophy was observed. CONCLUSION: Despite the increased AGA positivity found distinctively in patients with recent-onset RA, none of the RA patients showed clear evidence of coeliac disease. AGA positivity in early RA may indicate a role of the gut immune system in the initiation of RA. |