Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 3485482 | Autoantibodies to human nuclear antigen(s)-HNA-in connective tissue diseases and other dis | 1986 Jan | Autoantibodies reacting with nuclear antigen(s) on human cells (HNA) with weak or without reactivity on nuclei of other species have been found by the indirect immunofluorescence technique used in routine tests for the diagnosis of autoimmune diseases. Precipitin lines were obtained by counterimmunoelectrophoresis (CIE) only when human lymphocyte extracts were used and not with rabbit thymus acetone powder. By comparison with reference sera, the autoantibodies directed to HNA were found to be different from SSA/Ro antibodies and did not give the fluorescence pattern of anti nuclear mitotic apparatus (NuMA) antibodies on HEp-2 cells. The prevalence of sera with anti-HNA antibodies not associated with other antinuclear antibodies (ANA) is low (about 0.7% of ANA found in routine assay). In association with ANA of other specificities, the prevalence of anti-HNA antibodies, demonstrated after absorption of sera with rat liver acetone powder, was higher (about 1% of ANA positive sera). By treatment with physicochemical agents and enzymes, the HNA was found to be a DNA (glyco)-protein complex extractable with saline solution, resistant to 56 degrees C for 6 h and stable at pH values ranging from 3 to 10. Anti-HNA antibodies were found in patients with mild connective tissue diseases, but also in idiopathic interstitial pneumonia and in chronic hepatitis. | |
| 3237695 | Pathology of primary congenital complete heart block. | 1988 Mar | Studies were done on the hearts of 4 infants and 2 adults with the clinical diagnosis of congenital complete heart block (CCHB) and on the hearts of 6 control patients of similar age groups but without any significant arrhythmia. All 6 patients with CCHB had absence of the fibers [approaches to atrioventricular node (AVN)] connecting the atrium and the AVN and common bundle (CB), as well as having partial or complete absence of the AVN. The mothers of 2 of the 4 infants with CCHB had antibodies to Ro antigen, and one mother (with Ro antibody) had evidence of having had active systemic lupus erythematosus (SLE). One infant developed SLE before the age of 1 yr. In one of the 2 adult cases with CCHB, the patient had evidence of having developed his CHB after birth, and the other adult patient probably had his CCHB since birth. It was suggested that these findings--and others in the literature--could be explained by there being two factors that lead to the occurrence of idiopathic heart block, whether it be truly congenital or acquired later in life: (a) a genetic predisposition to the condition together with (b) a precipitating injury. Thus, a patient with a genetic predisposition to insults to his conducting fibers might develop CCHB in utero due to some insult (e.g., due to damage by circulating anti-DNA antibodies in patients with SLE or by other unknown insults); or the "weak" fibers could be affected later in life by many different injuries--whether viral, hypersensitivity, anoxic, or due to aging. | |
| 1799186 | Clinicopathological findings of bucillamine-induced nephrotic syndrome in patients with rh | 1991 | This paper describes pathological and clinical investigations of glomerular lesions in bucillamine-induced nephropathy by analyzing biopsy materials from 9 patients with rheumatoid arthritis (RA). There was no specific predisposition for nephrotic syndrome induced by bucillamine in clinical profiles related to age, onset, duration of disease, sex, activity and dose of bucillamine. In light-microscopic, electron-microscopic and immunofluorescent findings, the characteristic changes were similar to those of idiopathic membranous glomerulonephritis (MGN). After discontinuance of bucillamine, the nephrotic syndrome improved slowly with or without corticosteroid therapy. Results confirmed that the most common lesion of nephrotic syndrome associated with bucillamine therapy in RA is MGN. We recommend that corticosteroid therapy should be restricted to cases with severe proteinuria. | |
| 2209707 | Detection of interleukin 8 biological activity in synovial fluids from patients with rheum | 1990 Sep | The presence of neutrophils in the synovial joint of patients with rheumatoid arthritis (RA) is thought to be due to the activity of chemotactic factors released by activated cells in the joint. We have shown in this report, for the first time, the abundance of one such factor, interleukin 8 (IL 8), in the synovial fluid of patients both with RA and other non-RA joint diseases, and the spontaneous production of IL 8 mRNA by RA synovial cells in culture. There was no correlation between the levels of chemotactic activity and IL 8 protein, suggesting that other factors with similar neutrophil chemotactic activity are also present in the synovial fluid exudate. In support of this concept neither the level of chemotactic activity nor IL 8 protein levels correlated with neutrophil or leukocyte infiltration, indicating that the mechanism of migration into the inflammatory environment of the joint is complex. Such migration is likely to be due to a number of chemotactic signals in addition to IL 8, which may either synergize with, or inhibit, the action of IL 8. | |
| 2874329 | T lymphocytes of rheumatoid arthritis patients show augmented reactivity to a fraction of | 1986 Aug 9 | An acetone-precipitable fraction of Mycobacterium tuberculosis cross-reacts with human cartilage. Immune responses to this antigen were assessed in 34 patients with rheumatoid arthritis, 16 patients with degenerative joint disease, and 15 healthy controls. The RA patients differed from the other two groups in having more pronounced T lymphocyte responses to the antigen; their serum antibody levels were not higher. The responses of RA patients varied with duration of disease. In the first year (7 patients) T lymphocyte reactivity was increased in the synovial exudates of affected joints but not in peripheral blood, whereas the 19 with disease of 1-10 years' duration showed high reactivity in peripheral blood; in the 8 with disease for more than 10 years, lymphocyte reactivity did not differ from that in the patients with degenerative joint disease or the healthy controls. The observation that the three groups did not differ in their responses to streptococci and a T-cell mitogen indicates that reactivity of the RA patients to the mycobacterial fraction was specific. These results raise the possibility that bacterial antigens cross-reactive with cartilage proteoglycans may be relevant to the pathogenesis of RA. | |
| 3514310 | A long-term study of flurbiprofen in rheumatological disorders: I. Rheumatoid arthritis. | 1986 | Eight hundred and forty-two patients undergoing treatment for rheumatoid arthritis in hospital centres in the United Kingdom were evaluated as part of a long-term, variable dose study of the efficacy and safety of flurbiprofen in 1,396 patients with a variety of rheumatological disorders. Highly significant (p less than 0.001) improvements were evident in morning stiffness, grip strength, joint size, articular index and functional capacity at the end of the 18-month observation period reported here, as was a decrease in pain severity in all sub-groups, including those patients entering the study because of lack of effect of their previous therapy. Global assessments by doctor and patient showed highly significant improvements over this time period for both young and older patients, in whom objective improvements were less striking. Sixty-four per cent of side-effects reported were gastro-intestinal, CNS side-effects (headache, giddiness) accounting for 14%. The incidence varied according to whether or not concomitant therapy was being prescribed. Side-effects in the elderly were similar in nature to those in younger patients. | |
| 2784042 | Interleukin-2 in scleroderma: correlation of serum level with extent of skin involvement a | 1989 Mar 15 | STUDY OBJECTIVE: To assess whether interleukin-2 has a role in the pathogenesis of scleroderma. DESIGN: Observe serum effect on the in-vitro growth of an interleukin-2-dependent cytotoxic T-cell line and determine serum level by an enzyme-linked immunosorbent assay. SETTING: Outpatient rheumatology clinic of a university medical center. PATIENTS: Sera were collected from 47 patients with scleroderma, 20 patients with rheumatoid arthritis, and 14 matched control subjects. MEASUREMENTS AND MAIN RESULTS: A significant mitogenic effect was observed in sera from patients with scleroderma of recent onset; a lower proliferative response was seen in rheumatoid sera. Matched control sera had no mitogenic activity. Sera from patients with scleroderma of recent onset supported the in-vitro growth of an interleukin-2-dependent cytotoxic T-cell line. Matched control sera had no similar mitogenic activity. Interleukin-2 was found in sera from 41 of 47 patients with scleroderma (204 +/- 356 U/mL, mean +/- SD), in 9 of 20 patients with rheumatoid arthritis (2.04 +/- 5.16), and in none of 14 matched control subjects. There was a positive correlation between serum level and the skin progression index (skin score/disease duration). CONCLUSIONS: The presence of interleukin-2 in scleroderma sera strongly supports a role for T-cell activation in scleroderma. The association between serum levels and disease progression indicates that this T-cell process may participate in the progression of the disease. | |
| 2515595 | B-cell growth-promoting activity in supernatants from CD4+ cells from synovial fluid and p | 1989 | The purpose of this study was to compare CD4+ cells from peripheral blood (PB) and synovial fluid (SF) of patients with rheumatoid arthritis with regard to mitogen-induced production of B-cell growth-promoting activity. CD4+ cells were isolated by a direct immunomagnetic technique and supernatants from both unstimulated and mitogen-stimulated CD4+ cells were studied. B-cell growth-promoting activity was assayed using highly purified B cells obtained from peripheral blood of healthy individuals. The indicator B cells were isolated by an indirect immunomagnetic technique and solid-phase anti-mu was used for activation of the B cells. Supernatants of unstimulated CD4+ cells from SF and PB did not contain B-cell growth-promoting activity, while usually high levels of B-cell growth-promoting activity were detected in the supernatants from mitogen-stimulated cultures. There was no significant difference in the B-cell growth-promoting activity level between supernatants from SF CD4+ and patient PB CD4+ cells, nor was there any significant difference between SF CD4+ and control PB CD4+ supernatants. The results indicate that the CD4+ cells in the SF have a normal potential for producing B-cell growth-promoting activity. | |
| 2431451 | Granulocyte elastase as a new biochemical marker in the diagnosis of chronic joint disease | 1986 | Human granulocyte elastase (EC 3.4.21.37) is released from granulocytes in large amounts in chronic inflammatory joint diseases and is therefore of special pathogenic and diagnostic importance. In order to examine the diagnostic significance of this enzyme as a clinico-chemical parameter, we determined the concentration of granulocyte elastase in complex with alpha 1-proteinase inhibitor by an enzyme immunoassay in synovial fluids and plasma of patients with chronic joint diseases. In inflammatory synovial fluids the concentration of complexed elastase correlates well with the granulocyte number and may increase to an extremely high level. In 90% of patients with manifest rheumatoid arthritis increased elastase levels are also observed in the plasma, probably due to the large gradient between the synovial fluid and plasma concentration, whereas in osteoarthrosis normal plasma concentrations were observed. Thus, these results indicate that normal plasma concentrations in patients with chronic joint diseases exclude the diagnosis of rheumatoid arthritis with high probability. The simultaneous determination of complexed elastase in plasma and synovial fluid improves the nosological differentiation of chronic joint diseases. Elastase activity on a specific chromogenic substrate, which was found in many inflammatory synovial fluids, is mainly attributed to elastase alpha 2-macroglobulin complexes. In some purulent synovial fluids, however, we were able to detect free elastase, which has been shown to play an important role in the destruction of articular cartilage. | |
| 3395419 | Arthroscopic synovectomy of the knee joint: indication, technique, and follow-up results. | 1988 | Between 1981 and 1986, at the Orthopaedic Clinic of the University of Düsseldorf, arthroscopic synovectomy of the knee was performed on 59 joints in 56 patients. The follow-up examination covered 45 knee joints in 43 patients (18 female and 27 male patients). The follow-up results, taken at an average of 2.7 years after the arthroscopic synovectomy, have up to now been good and equal to those achieved using the conventional technique. In this experience, arthroscopic synovectomy is a surgical procedure that places less strain on the patient in the early postoperative healing period. An arthrotomy was no longer required in the hypertrophic synovial diseases treated during this time. Fibroarthrosis, not uncommon after conventional arthrotomy, did not occur. Only a few stab incisions were necessary to reach all--in particular the posterior--knee-joint cavities. Postoperative pain was markedly reduced from a preoperative level of 16.6 points (47%) (35 maximum points possible, or 100%) to a level of 29.5 points (84%) at follow-up. Patients who experienced an open synovectomy previously in the other knee now favor the arthroscopic procedure. The majority of the patients had a range of motion between 0 and 120 degrees within the first 2 weeks after surgery. Swelling disappeared from a preoperative score of 2.9 points (19%) (15 maximal points possible, or 100%) to 12.2 points (81%). Subjectively, 78% of the patients were satisfied with the result of arthroscopic synovectomy, 7% considered the procedure a partial success, and 15% were dissatisfied. | |
| 3324305 | The pathogenesis and consequence of non steroidal anti-inflammatory drug induced small int | 1987 | Non steroidal anti-inflammatory drugs (NSAID's) have recently been shown to cause small intestinal inflammation in the majority of patients receiving these on a regular basis for more than one year. The development of inflammation is preceded by an NSAID effect to increase small intestinal permeability. Increased intestinal permeability is shown to be related to drug potency to inhibit cyclooxygenase and the effect is systemically mediated rather than a local irritant one. More recently, increased intestinal permeability due to NSAID's has been reduced by concomitant prostaglandin administration, showing that prostaglandins are essential for maintaining intestinal integrity in man. It is proposed that altered intestinal permeability allows the mucosa to be exposed to bacterial degradation products or other toxins and together with reduced chemotaxic response and altered neutrophil function due to NSAID's, this series of events leads to bacterial invasion of the mucosa which is evident by the techniques of 111Indium leucocyte scans and faecal collections. The consequence of such inflammation is that it may explain intestinal perforations and strictures which are occasionally seen in subjects on NSAID's. Most patients with NSAID-induced small intestinal inflammation may be bleeding from the intestine, loosing protein and some have ileal dysfunction. The small intestine may be a greater source of morbidity than the stomach, in patients receiving NSAID's. | |
| 1927062 | Serum lipid pattern and apolipoproteins (A1 and B100) in active rheumatoid arthritis. | 1991 May | Cardiovascular diseases and atherosclerotic manifestations have been reported to be the most common causes of death in rheumatoid arthritis (RA). In the present investigation the levels of serum lipids, apolipoproteins (A1 and B100), total proteins, and albumin were studied in 35 female patients affected by active RA. Apolipoproteins A1 and B100 were significantly lower in RA patients than in controls. No significant difference was observed in total cholesterol, LDL cholesterol, or triglycerides. In contrast, HDL cholesterol and serum albumin were significantly lower in RA patients compared to controls. The finding of reduced apolipoproteins and HDL-cholesterol levels may represent an important factor in the etiology of cardiovascular and atherosclerotic disease in RA. Reduced levels of albumin in active RA may indicate a reduced rate of proteins like lipoproteins in the liver. | |
| 2542541 | Altered formation of leukotriene B4 in vitro by synovial fluid neutrophils in rheumatoid a | 1989 Mar | The synthesis of products of the 5-lipoxygenase pathway by synovial fluid (SF) and peripheral blood neutrophils of 12 patients with rheumatoid arthritis was compared in 3 experimental conditions using high performance liquid chromatographic analysis. Major differences were observed when blood and SF neutrophils were incubated with ionophore A23187, the formation of all 5-lipoxygenase products being lower (p less than 0.0005) in the SF neutrophils. Addition of exogenous arachidonic acid to the A23187 stimulated cells partially overcame the difference in 5-lipoxygenase product synthesis between the 2 neutrophil populations. In contrast, upon incubation with arachidonic acid alone, SF neutrophils produced significantly larger amounts of 5-lipoxygenase products. The increased reactivity of the SF neutrophil 5-lipoxygenase to arachidonic acid and the decreased 5-lipoxygenase product synthesis upon A23187 stimulation may be the consequence of the previous activation of the cells and 5-lipoxygenase product synthesis in situ. | |
| 3289386 | Natural history of alpha-1-protease inhibitor deficiency. | 1988 Jun 24 | Alpha-1-protease inhibitor (A1PI) exists in over 30 biochemical variants (the Pi system), inherited as autosomal codominant alleles. Homozygotes of Pi type Z have only 10 to 20 percent of the normal serum A1PI concentration and have a high risk of developing pulmonary emphysema. A1PI is an inactivator of polymorph lysosomal elastase, the unopposed action of which may damage the lung. Cigarette smoking is an important additional risk factor. Neonatal hepatitis occurs in 10 to 20 percent of Pi type Z persons, and cirrhosis develops in a number of them in later childhood or in adult life. In heterozygotes of Pi type MZ, pulmonary or hepatic disease may also develop, though they are at lesser risk than type Z homozygotes. Specific A1PI replacement therapy derived from human plasma is now available and has been administered to Pi type Z patients by weekly intravenous infusion without adverse effects. A controlled clinical trial would be desirable, though this would be attended by organizational and economic problems. | |
| 3361544 | Postmarketing surveillance in rheumatology: analysis of purpura and upper abdominal pain. | 1988 Feb | A system of postmarketing surveillance of antirheumatic drugs employing prospective protocol based consecutive patient cohorts is described, together with use of recursive partitioning techniques for statistical adjustment for potentially confounding variables. An analysis of 2 side effects (purpura and upper abdominal pain) is presented. Purpura was found to be associated with age, sex, disease duration, and amount of disability. The combination of aspirin and prednisone was associated with the highest prevalence of purpura. Upper abdominal pain also varied across drug classes. Within the nonsteroidal antiinflammatory drug category, there were clinically important differences in the relative prevalence of upper gastrointestinal pain between specific drugs. | |
| 3356714 | The cemented kinematic-II and the non-cemented porous-coated anatomic prostheses for total | 1988 Apr | One hundred and sixty consecutive total knee arthroplasties were performed in 143 patients: 110 procedures, with a cemented kinematic-II prosthesis and fifty procedures, with a non-cemented porous-coated anatomic prosthesis. Each patient was evaluated before the operation and six weeks and three, six, twelve, and twenty-four months postoperatively. At a minimum twenty-four-month follow-up, the average Hospital for Special Surgery knee-rating score for the patients who had a cemented kinematic-II prosthesis was 9 points higher than the average score for the patients who had a non-cemented anatomic implant (88 points and 79 points). At the same follow-up period, the maximum flexion of the knees that had a cemented kinematic-II prosthesis was greater than that of the knees that had a non-cemented anatomic prosthesis (106 degrees and 97 degrees). In addition, the rate of reoperation for the patients who had a cemented kinematic-II replacement was 4 per cent, compared with 12 per cent for the patients who had a non-cemented anatomic prosthesis. On the basis of this prospective, non-randomized clinical review of unselected patients, we concluded that the results with the cemented kinematic-II prosthesis were superior to those with the non-cemented anatomic prosthesis at a minimum twenty-four month follow-up; however, these superior results may be related to the use of cement or to differences in the designs of the prostheses, the ages of the patients, or the postoperative management of the two groups of patients. | |
| 2181675 | NSAID-induced gastric injury: its pathogenesis and management. | 1990 Feb | Injury to the gastric mucosa associated with the use of aspirin and other NSAIDs appears to be principally attributable to impairment of mucosal defense mechanisms against damage by acid and pepsin, that are mediated largely by prostaglandins. Modification of the drug dose or delivery system and substitution of a less gastrotoxic agent, such as a nonacetylated salicylate, are among the initial approaches that have been used to reduce the risk of NSAID-induced gastric injury. Other recommended measures include the avoidance of cigarettes, concentrated alcohol, and combination therapy with multiple NSAIDs. In high-risk patients, especially those with previous peptic ulcer disease, prophylactic therapy with a cytoprotective or acid-secretion-reducing drug is indicated. Drugs often used in the treatment of NSAID-associated mucosal damage include H2-receptor blockers, which inhibit gastric acid secretion, and agents such as synthetic prostaglandins and sucralfate, which improve mucosal defense. More potent inhibitors of gastric acid, such as drugs which block H+/K+ ATPase, may offer improved results for healing NSAID-induced gastric ulcers resistant to other therapy. Because NSAID-induced gastric lesions are not always accompanied by symptoms, patients receiving these drugs must be closely monitored for signs of gastric injury. Small ulcers can generally be healed with antiulcer medications. In patients with larger ulcers, withdrawal of NSAID therapy is usually required, at least until healing has occurred. | |
| 1660324 | Thrombomodulin expression by human blood monocytes and by human synovial tissue lining mac | 1991 Dec 15 | Thrombomodulin is an essential cofactor for the activation of the anticoagulant protein C by thrombin. We have identified the expression of thrombomodulin messenger RNA (mRNA) and protein in peripheral blood monocytes. While untreated monocytes expressed thrombomodulin mRNA by Northern blot analysis, lipopolysaccharide-treated cells had decreased mRNA expression. Thrombomodulin antigen was shown in the cytoplasm and on the surface of monocytes by immunohistochemical staining, and thrombomodulin activity was shown on the surface of intact monocytes. One population of synovial lining cells that normally expressed mononuclear phagocyte antigens also expressed thrombomodulin in both noninflamed osteoarthritic synovium and in inflamed rheumatoid arthritis synovium. However, these cells did not express another endothelial protein, von Willebrand factor. We conclude that both circulating and tissue mononuclear phagocytes are capable of expressing thrombomodulin. | |
| 2397609 | Reactive oxygen species modify human DNA, eliciting a more discriminating antigen for the | 1990 Sep | During the development of an ELISA to measure anti-DNA antibodies in systemic lupus erythematosus (SLE) sera, native dsDNA was found not to be the most appropriate antigen to use in ELISA assays for differentiating between SLE patients and those with rheumatoid arthritis (RA), a disease also associated with circulating serum anti-DNA antibodies. By modifying the ELISA technique to incorporate human DNA, denatured by reactive oxygen species, to detect anti-DNA antibodies in SLE sera, results consistently showed an increase in antibody binding when compared with the native antigen; no such trend was observed in the comparable group of RA patients. Using this assay serum anti-dsDNA antibody levels were measured in a group of 20 controls, 20 RA patients (10 seropositive and 10 seronegative) and 30 SLE patients (15 with clinically active disease, 15 with inactive disease). A comparison with the standard radioimmunoassay used to measure anti-DNA antibodies for the diagnosis of SLE showed that the ELISA assay using modified DNA performed better than the standard radioimmunoassay offering an improvement in both clinical specificity and sensitivity. The improved method particularly reduced the problem of false-negative results for SLE patients shown clinically to be either mildly active or inactive. | |
| 2479495 | Changes in concanavalin A-reactive proteins in inflammatory disorders. | 1989 Nov | Quantitative changes of concanavalin A (Con A)-reactive proteins in serum samples obtained from rats with induced inflammation and from patients with inflammatory and autoimmune diseases were examined by use of lectin blots. Treatment of rats with a single dose of fermented yeast to induce inflammation caused an extensive increase in Con A-reactivity. These changes were time dependent and were similar in both sexes of the animals. When we examined serum samples obtained from patients with various inflammatory disorders for their Con A-reactive proteins as compared with normal donors, we noted that the Con A-reactivity increased in patients with rheumatoid arthritis and systemic lupus erythematosus. Among all the glycoproteins examined by lectin blots with use of Con A, a set of five proteins was selected for detailed analysis by densitometric scanning. These included alpha 2-macroglobulin, P-150, P-95, P-40, and P-35, of Mr 180,000, 150,000, 95,000, 40,000, and 35,000, respectively, by sodium dodecyl sulfate-polyacrylamide gel electrophoresis under reducing conditions. Densitometric scanning analysis of the lectin blots revealed that the Con A-reactivity of these proteins increased during inflammation. Because alpha 2-macroglobulin is not an acute-phase protein in humans, an increase in Con A staining of this protein suggested that altered glycation is associated with autoimmune diseases. Thus, study of changes in Con A-reactive proteins in human sera may facilitate our understanding of the etiology and pathophysiology of autoimmune diseases. |