Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 1662480 | Detection of Epstein-Barr virus and human herpes virus type 6 in saliva from patients with | 1991 | Direct detection of these viruses was made by using the PCR for amplifying viral DNA. In virtually all adults low levels of the herpesvirus can be detected. Therefore it is necessary to quantitate the amount of viral DNA, and a method to compare the plasmid containing the cloned target gene was used here. After 35 cycles of amplification, 10 copies of the viral DNA per 100 microliters saliva were detected. The PCR was used to detect increased levels of EBV and HHV-6 in saliva from patients with lymphoproliferative diseases, suggesting that these viruses may play a part in their pathogenesis. Viral detection by such highly sensitive methods as PCR may allow better monitoring of medication, as well as early detection of EBV- and HHV-6 related diseases that may arise in these patients. The great sensitivity of PCR and its ability to analyse very small samples make this technique most suitable for clinical diagnosis. | |
| 3304739 | Ligand-binding and idiotypic cross-reactions between anti-DNA antibodies and antibodies to | 1987 Sep | Antibodies to DNA and K30p were purified by affinity procedures and tested for their ability to cross-react with K30p and DNA, respectively. Anti-ssDNA antibodies were shown to react with solid-phase K30p and be inhibited in a dose-dependent manner by soluble ssDNA and K30p. Conversely, anti-K30p antibodies were found to bind immobilized ssDNA and be inhibited with soluble inhibitor. These results show that certain subpopulations of anti-ssDNA and anti-K30p antibodies overlap in their ligand-binding specificities. Idiotypic (Id) analysis showed that anti-K30p antibodies did not react significantly with an anti-Id reagent directed against a common anti-DNA framework Id (AM Id), thus clearly separating K30p-binding anti-DNA antibodies into an AM Id-negative population. When anti-DNA antibodies were probed with an anti-Id reagent directed against a framework Id present on anti-K30p antibodies (SP Id), substantial reactivity was found. Thus the SP Id identifies a subpopulation of antibodies capable of binding both K30p and DNA. These results show that a subset of anti-ssDNA antibodies cross-react with K30p antigen and are idiotypically related to a subset of antibodies reactive with K30p. | |
| 2214602 | [Plasma endothelin in normal probands and patients with nephrologic-rheumatologic and card | 1990 Aug 2 | Plasma concentrations of the recently isolated potent vasoconstrictory peptide endothelin were measured in 382 patients. The investigations were performed by means of a sensitive radioimmunoassay specific for Endothelin-1, 2. The results from 110 healthy volunteers displayed a normal range of 44.67 +/- 3.51 pg/ml. Significantly raised levels were found in 33 patients with chronic end-stage renal failure both before and after hemodialysis. In contrast, 35 patients with compensated renal insufficiency did not differ from the normals. Sixty-five patients after kidney transplantation revealed significantly elevated levels, as did 27 patients with acute myocardial infarction, 8 after coronary bypass surgery, and 5 with liver cirrhosis. The mean values of 27 patients with untreated hypertension, 22 with secondary hypertension, of various causes and 16 with coronary artery disease were comparable to the normal population. The values were significantly decreased in 9 pregnant women with hypertension and proteinuria. A marked decline was found in 5 patients with systemic lupus erythematodes, while 20 patients with rheumatoid arthritis demonstrated only a slight decrease. The pathophysiological role of endothelin as a local or circulating hormone in regulating systemic blood pressure or release of other hormones remains to be determined. | |
| 2479078 | Application of an enzyme-linked immunosorbent-inhibition assay to quantitate the release o | 1989 | The effects of the chondroprotective agents (Arteparon, SP-54 and DH40J) on the release of proteoglycan degradation products (as keratan sulphate peptide fragments) from articular cartilage implanted into rat subcutaneous air pouches have been investigated by using an enzyme-linked immunosorbent-inhibition assay (ELISIA). The ELISIA technique was capable of quantitating the keratan sulphate peptides (KS peptides) in fluids within the range of 100-2,000 ng/ml by using the monoclonal antibody line 1/20/5-D-4 and human articular cartilage KS peptides as standard reagents. It was found that the levels of KS peptides present in the air-pouch fluid of rats treated with the chondroprotective drugs was significantly less than in fluid aspirated from the pouches of non-drug-treated control animals. On the basis of these findings we suggest that the assessment of KS peptide by ELISIAs may provide a useful means of monitoring proteoglycan breakdown products in biological fluids (e.g. synovial fluids or blood) and for evaluating the effects that antiarthritic drugs may have on this process. | |
| 1940389 | Production of monoclonal antibodies against inactivated alpha 1-antitrypsin. Cross-reactiv | 1991 Oct 25 | 15 different monoclonal antibodies (mcAbs) have been raised against the cleaved (inactive) form of the serpin alpha 1-antitrypsin (AT). In initial experiments these mcAbs were analysed for their ability to bind the native and the cleaved form of this inhibitor: eight of the 15 mcAbs appeared to react predominantly with cleaved AT. Additional experiments with mixtures of purified native AT, AT complexed to neutrophilic elastase and inactivated AT revealed that all mAbs that preferentially reacted with inactivated AT also bound to complexed AT. Using two of the mcAbs against inactivated AT a quantitative and sensitive sandwich-type radioimmunoassay was developed to determine levels of proteolytically inactivated AT in biological fluids. With this assay increased levels of inactivated AT were found in synovial fluid from patients with rheumatoid arthritis corresponding to about 2.4% (range 0.3-11%) of total AT. Approximately 10% of this inactivated AT appeared to consist of AT complexed to neutrophil elastase. The mcAbs described here further illustrate the structural resemblance between the complexed and cleaved forms of AT. In addition, these mcAbs appear to be useful tools for the study of AT in human disease. | |
| 1696227 | Pancreatic cytokeratin: an antigen of pancreatic exocrine cell autoantibodies in type 1 (i | 1990 Jun | Autoantibodies reacting with human pancreatic exocrine cells were investigated by immunofluorescent techniques in 107 patients with Type 1 (insulin-dependent) diabetes mellitus, 20 first-degree relatives of the Type 1 diabetic patients, 347 patients with Type 2 (non-insulin-dependent) diabetes, 34 with alcoholic pancreatitis, 26 with rheumatoid arthritis and 107 normal control subjects. Both immunoblotting analysis and double-immunostaining methods were used to characterize the antigens targeted by the pancreatic exocrine cell autoantibodies. Sera positive for human pancreatic exocrine cell cytoplasm, producing a "fine fibrillar" pattern, were found in 21% (23/107) of the Type 1 diabetic patients. The autoantibodies were present in 39% (15/38) of Type 1 diabetic patients diagnosed within 3 months, and the prevalence decreased with duration of diabetes. The antibodies were of the IgM class in 87% (13/15) of recent-onset Type 1 diabetes cases, but IgG-autoantibodies became more prevalent with increasing duration of diabetes. Three out of 347 (0.9%) Type 2 diabetic patients and 4 of 20 (20%) first-degree relatives of Type 1 diabetic patients had autoantibodies targeted against pancreatic exocrine cells. None of the patients with alcoholic pancreatitis or rheumatoid arthritis and none of the control subjects had these antibodies. Immunoblotting analysis and double-immunostaining demonstrated that the autoantibodies reacted with 40 kilodalton cytokeratin in pancreatic exocrine cell cytoplasm. The antibody was absorbed by the Triton X-100-insoluble fraction of pancreatic extract. These results indicate the presence of distinct autoantibodies to pancreatic exocrine cells in Type 1 diabetes. This suggests the provocative concept that the cytoskeletal system of pancreatic exocrine cells is involved in the pathogenetic process of Type 1 diabetes. | |
| 1941816 | The clinical course of Felty's syndrome compared to matched controls. | 1991 Aug | In a cohort of 919 patients with definite or classic rheumatoid arthritis followed prospectively since 1966, we identified 36 patients with Felty's syndrome (FS). Their clinical course was compared to that of 72 matched controls from the same cohort. Patients with FS had more extraarticular features and more infections than control patients. The presence of joint erosions, serial Lansbury indices, and death rates were similar in both groups. Cardiovascular disease was the commonest cause of death in both groups, accounting for 32% of all deaths. Sepsis accounted for 10% of deaths in the group with FS and 13% of deaths in the controls. | |
| 3720025 | Studies of the effect of mitoxantrone on adjuvant induced arthritis in rats. | 1986 Aug | When rats with developing or established adjuvant arthritis are treated with mitoxantrone, the hind paw inflammation associated with the disease is inhibited. Radiographic analysis of the hind paws indicates that the agent suppresses joint destruction associated with the lesion. Comparative studies with cyclophosphamide indicate that mitoxantrone is more efficacious and at least 20 times more potent than cyclophosphamide. Mitoxantrone also appeared more effective when given by the subcutaneous route than the peritoneal route of administration. | |
| 2347546 | Sjögren's syndrome in patients with primary biliary cirrhosis. | 1990 May | Symptomatology and objective findings of Sjögren's syndrome were evaluated in 38 consecutive patients with primary biliary cirrhosis. Symptoms of Sjögren's syndrome were present in 18 (47.4%) patients, but were severe enough to warrant therapy in only four (10.5%). Nineteen patients consented to evaluation for Sjögren's syndrome, which included Schirmer's I test, measurement of parotid flow rate and serum autoantibodies, labial minor salivary gland biopsy and human leukocyte antigen typing. Histological changes diagnostic of Sjögren's syndrome were present in five patients (26.3%). All five patients had symptoms of Sjögren's syndrome and three had abnormal Schirmer's I tests, but none had corneal ulcerations or decreased parotid flow rates. Results of serological tests and human leukocyte antigen typing were not similar to those described in patients with primary Sjögren's syndrome but were similar to those described in patients with rheumatoid arthritis and Sjögren's syndrome. These findings indicate that Sjögren's syndrome associated with primary biliary cirrhosis is a form of secondary Sjögren's syndrome resembling that associated with rheumatoid arthritis. | |
| 3700003 | Ultrastructural study of neuromuscular and vascular changes in connective-tissue diseases. | 1986 | Ultrastructural changes of the neuromuscular and microvascular systems were investigated in muscle biopsies obtained from patients with rheumatoid arthritis, systemic lupus erythematosus, dermato- and polymyositis and progressive systemic sclerosis. Myofibrillar degeneration, Z-disc streaming, mitochondrial abnormalities, alteration of the T system and sarcoplasmic reticulum were the main ultrastructural alterations observed in biopsy material. At the same time, severe peripheral nerve-fibre lesions were also observed. Thickening of the basement membrane around capillaries was repeatedly demonstrated, above all in rheumatoid arthritis and progressive systemic sclerosis. Immunocomplexes around capillaries and small vessels as well as along the sarcolemmal basement membrane were also often demonstrated. | |
| 3230564 | Detection of the major rheumatoid factor cross-reactive idiotype precedes human IgG bindin | 1988 Dec | A patient with polyarthritis and subcutaneous nodules was studied for expression of rheumatoid factors (RF) by numerous techniques for 5 months after presentation. Assays for RF binding human or rabbit IgG in whole sera, assays for hidden RF binding human or rabbit IgG, and assays for expression of the major RF cross-reactive idiotype (RCRI) in whole sera or by pokeweed mitogen induced plasma cells were performed (PWM-PC). In this patient, increased expression of RCRI in sera and among PWM-PC preceded detectable RF binding human IgG, and paralleled hidden RF and RF binding rabbit IgG expression. | |
| 3498592 | Phenotype of peripheral blood lymphocytes in patients with progressive systemic sclerosis: | 1987 Aug | To understand better the role that immune mechanisms could play in the pathogenesis of progressive systemic sclerosis (PSS), the phenotypes of peripheral blood lymphocytes (PBL) from 24 PSS patients and normal controls were compared by a panel of monoclonal antibodies. PBL T cells of patients expressed an increased percentage of several activation markers as defined by monoclonal antibodies B33.1 (anti-Ia), TAC (anti-interleukin 2 receptor) and 5E9 (anti-transferrin receptor). These antigens were also found on PBL of patients with quiescent disease suggesting the persistence of an ongoing immune response despite the absence of clinically apparent disease activity. Patients treated with D-penicillamine had uniformly normal proportions of Ia+ T cells (less than 5%) although the percentage of cells positive for Tac and transferrin receptor continued to be elevated. A second finding was that the percentage of natural killer (NK) cells studied with the monoclonal antibody against NK cells B73.1 (Leu 11c) and particularly an OKT8+ NK cell subset was low in patients (10.4 +/- 4.7) compared with controls (15.9 +/- 5.8). Finally, both treated and untreated patients displayed increased OKT4+/OKT5+ ratios compared to controls. These data suggest that PBL from PSS patients are activated and have abnormal proportions of cell subpopulations. These abnormalities are also present in patients with quiescent disease. The observed effect of D-penicillamine on Ia expression in PSS PBL may reflect a mechanism of action of this drug in the control of autoimmune diseases. | |
| 2181673 | Reduced risk of NSAID gastropathy (GI mucosal toxicity) with nonacetylated salicylate (sal | 1990 Feb | This randomized, investigator-blinded, parallel group endoscopic study evaluated the effects of salsalate and naproxen on the gastroduodenal mucosa over a 3-month period in patients with RA. Using therapeutic doses of the drugs, 8 of 21 patients (38%) in the naproxen group had endoscopically shown active ulcers (seven patients) or diffuse erosions (one patient), whereas none of the 18 patients treated with salsalate (0%) had such lesions (P = .003). Five of the eight naproxen-treated patients with evidence of GI damage were asymptomatic at the time of endoscopic verification of their lesions. The most significant disadvantage of salsalate was its higher incidence of otologic problems accounting for six of the nine discontinuations with salsalate. However, the findings of this study suggest that patients receiving salsalate are at lower risk for developing significant gastropathy than those treated with naproxen. The relative benefit-to-risk ratio of salsalate indicates that this drug should be considered as a significant alternative NSAID therapy. | |
| 2510276 | Prophylactic and therapeutic role of rioprostil in NSAIDs induced gastroduodenal lesions. | 1989 | In a randomized, double-blind, placebo-controlled, prospective trial, the activity of rioprostil, a new prostaglandin E1 alcohol analogue, on non-steroidal anti-inflammatory drug-induced gastroduodenal mucosal lesions is studied in 30 patients with rheumatic diseases. Both treatment regimens, rioprostil, 150 micrograms t.i.d., and rioprostil, 200 micrograms b.i.d., for a period of 12 weeks, significantly reduce the rate of mucosal lesions in all patients when compared to placebo. Furthermore, rioprostil achieves a reduction in gastrointestinal symptoms without enhancement of joint disease activity, and significantly reduces antacid intake. Therapy is safe and well tolerated by all patients. It can be concluded from this study that prostaglandins could play an important part in the prevention and treatment of gastrointestinal damage due to NSAIDs. | |
| 3330094 | Immunoregulating peptides II. In vitro effects of TP5 analogs on E-rosette formation and c | 1987 | The effects of seventeen synthetic analogs of thymopentin (TP-5) have been studied in the active and azathioprine-inhibited E-rosette tests. Thymopentin was gradually shortened from the C terminus to peptides and single amino acids. Thymopoietin 32-34 (Arg-Lys-Asp-RGH-0205-TP-3) (II) and thymopoietin 32-35 (Arg-Lys-Asp-Val-RGH-0206-TP-4) (I) were the most active peptides. Dipeptide Arg-Lys produced significant stimulatory effect on azathioprine (ED75) inhibited E-receptor. Treatment of azathioprine (ED75)-inhibited E-rosette forming cells (ERFC) with arginine or especially lysine increased the number of ERFC. Some of TP-4 analogs decreased further the number of ERFC decreased by azathioprine ED30. These "suppressive" peptides as well as TP-3 caused a partial arrest of K 562 cell proliferation up to 96 hours. Results suggest that TP-5 is not the smallest active fragment of thymopoietins, since peptides (TP-3 and TP-4) exhibit similar or higher T-cell membrane activation on E-receptor. Arginine, lysine, and acidic aspartyl residue seem to be a necessary basic structure to produce a cumulative chemical signal on the activity of T-lymphocytes. | |
| 2574207 | A CD4 cell is capable of transferring suppression of collagen-induced arthritis. | 1989 Dec 15 | Collagen-induced arthritis can be suppressed by i.v. injection of intact type II collagen (CII) but not type I collagen before immunization. To identify the mechanism mediating this suppression, splenocytes were obtained from mice injected with CII or OVA and administered to recipients that were subsequently immunized with CII. Mice receiving cells from donors injected with CII had a lower incidence of arthritis and lower antibody titers than those receiving cells from OVA-injected donors. Treatment of cells with 3000 rad of gamma-irradiation abrogated the suppression. To determine the phenotype of these donor cells, spleen cells were fractionated by adherence to plates coated with mouse anti-IgG to enrich for Thy-1+ phenotype. Thy-1+ cells injected into naive mice could significantly suppress arthritis. Further depletion of T cell subsets by panning revealed that depletion of CD4+ cells prevented the transfer of suppression whereas removal of CD8+ cells had no effect. Isolated CD4+ cells transferred into naive mice were also suppressive. Recently the Pgp-1 (Ly-24) Ag has been described to identify a unique memory subset of CD4+ cells when present on the cell surface. In CII-tolerized spleen populations, removal of the Pgp-1+ (Ly-24) subset of T cells abrogated suppression and transfer of isolated Pgp-1+ cells suppressed arthritis. These findings indicate that the Pgp-1+ subset of CD4+ cells can suppress collagen-induced arthritis and suggest that a CD4+ memory cell down-regulates autoimmunity. In addition, treatment of donor animals with cyclosporin, which inhibits the development of CD4+ cells, abrogated suppression. | |
| 2109776 | Quantitative analysis of cytokine gene expression in rheumatoid arthritis. | 1990 May 1 | Previous studies of the cytokine profile of rheumatoid arthritis (RA) have been primarily limited to the assessment of the levels of these mediators in synovial fluid (SF) or synovial tissues (ST) by biologic or immunologic assays. We have studied cytokine gene expression in RA by in situ hybridization of SF cells, enzymatically dispersed ST cells, and frozen sections of ST. RA ST cells (n = 7) were studied and a high percentage of cells hybridized to the following anti-sense probes: IL-6 = 19 +/- 3.3%; IL-1 beta = 9.9 +/- 1.7%; TNF-alpha = 5.8 +/- 1.4%; granulocyte-macrophage-CSF = 2.2 +/- 0.8%; transforming growth factor-beta 1 = 1.3 +/- 0.2% (p less than 0.05 for each compared to sense probes). Similar results were found using osteoarthritis ST cells, although the percentage of cells expressing the IL-6 gene (7.1 +/- 2.5%) was significantly less in osteoarthritis compared to RA. RA ST cells did not significantly bind the IFN-gamma probe (0.2 +/- 0.1% positive), although they were capable of expressing the IFN-gamma gene if stimulated with PHA. The OKM1+ population of ST cells (i.e., macrophage lineage cells) was greatly enriched for IL-1 beta and TNF-alpha, whereas the OKM1- population (lymphocytes, fibroblasts, and type B synoviocytes) was enriched for IL-6. The vast majority of cells expressing the IL-6 gene were non-T cells. Furthermore, hybridization to RA ST frozen sections localized IL-6 mRNA to the synovial lining layer, which is comprised of type A and type B synoviocytes. In contrast to the high level of cytokine gene expression observed in ST, SF cells did not hybridize significantly to any of the cytokine probes. If stimulated with LPS or PHA, SF cells expressed IL-1 beta or IFN-gamma genes, respectively. | |
| 2109076 | Recent advances in defining the role of misoprostol in rheumatology. | 1990 Feb | Recent findings suggest that the prostaglandin E1 analog misoprostol may be associated with significant antiinflammatory and immunomodulatory effects. The addition of misoprostol to diclofenac significantly reduced the effective dose of the latter in the carrageenan acute inflammation rat model. A number of in vitro and animal studies have shown that misoprostol substantially increases the immunomodulatory effect of cyclosporine or steroids, and a study in renal transplant recipients revealed that the addition of this agent to cyclosporine and steroid treatment produced a significant improvement in renal function and a marked decrease in the incidence of graft rejection. Further, other recent data suggest that misoprostol may exert a protective effect against the damage to cartilage that appears to be induced by some nonsteroidal antiinflammatory drugs by decreasing the synthesis of cytokines. Further studies of misoprostol in these various contexts are warranted. | |
| 2575282 | Polyclonal B-cell activation by bacteria that induce nonsuppurative sequelae. | 1989 | The polyclonal B cell activation (PBA) process induced by Klebsiella pneumoniae K34 (klebs) and Yersinia enterocolitica 03 (yers) was investigated. Both heat-inactivated bacteria and their cell wall biostructures (klebsM, muriene, protein I etc.) stimulate human blood B cells to differentiate into immunoglobulin-secreting cells without prior proliferation and without T cells. Klebs-activated B cells secrete mainly IgM and to a lesser degree IgG (mainly IgG2). The PBA process was regulated by CD4+ cells and monocytes, but not by CD8+ cells. While interleukin 2 is able both to induce proliferation and to enhance differentiation in klebs-activated B cell cultures, the low-molecular-weight B cell growth factor (BCGF) did not lead to a significant amount of 3H-thymidine uptake. In addition, in klebs-activated B cell cultures various anti-polynucleotide autoantibodies and the 16/6 idiotype were detectable. Thus, bacteria that induce nonsuppurative sequelae (e.g. klebs, yers) can use several mechanisms to overcome tolerance in their host. | |
| 3554614 | Erythrocyte insulin receptor in insulin autoimmune syndrome: effects of corticosteroid the | 1987 Feb | Changes in the erythrocyte insulin receptors were studied in a patient with insulin autoimmune syndrome before and after corticosteroid therapy. In this case, despite a quite low fasting plasma glucose value (29 mg/100 ml), a 75 g oral glucose tolerance test (OGTT) showed a diabetic curve and extremely high immunoreactive insulin (IRI) levels were observed. After 6 months duration of the disease, corticosteroid was given to the patient and hypoglycemic attacks disappeared with an improvement of the levels of plasma glucose. The number of insulin receptors decreased from 58 to 29 sites/erythrocyte and an increase in binding affinity or maximal binding ability were observed after the treatment with corticosteroid. These receptor changes, for the most part, might be derived from the steroid effects, since there were similar results when we administered steroid for a long term to a certain disease. There was a 20% reduction in the amount of insulin binding IgG purified from the serum one month after treatment with corticosteroid as compared with that purified from the serum before the treatment. The results suggest the usefulness of corticosteroid therapy in treatment of the insulin autoimmune syndrome. |