Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 3759100 | Decrease of transferrin C2 frequency with age. | 1986 | In previous studies, transferrin C2 has been found to be associated with spontaneous abortion, prematurity, phototoxic eczema and rheumatoid arthritis. We have suggested that the mechanism behind these negative effects may be that transferrin C2 increases the risk for damage through hydroxyl radicals. This hypothesis predicts that the C2 frequency should decrease with age. Such an effect is demonstrated in this report. In a population from northern Sweden the C2 gene frequency was found to decrease from 0.173 in newborns to 0.099 in 70-year-old healthy individuals. | |
| 2053916 | T cell responses to polypeptide fractions of Borrelia burgdorferi in patients with Lyme ar | 1991 Jun | Among 6 patients with prolonged episodes of Lyme arthritis, the mean response of peripheral blood lymphocytes (PBL) to all Borrelia burgdorferi antigens (stimulation index [SI] 46) was greater than that among 5 patients with brief attacks of Lyme arthritis (SI 13; P less than 0.1), as well as that among 7 control patients with rheumatoid arthritis and among 6 normal control subjects (in both instances SI 3; P less than 0.05). In individual patients with brief episodes of Lyme arthritis, PBL had similar low levels of reactivity with the 20-kd, 31-kd, 34-kd, 41-kd, 55/58-kd, and 66-kd spirochetal polypeptides. In individual patients with prolonged arthritis, PBL usually had similar marked responsiveness to the 34-kd, 41-kd, 55/58-kd, and 66-kd polypeptides, but they had greater reactivity with the 34-kd outer surface protein B than with the 31-kd outer surface protein A (P less than 0.05). In the 2 patients tested, paired samples of synovial fluid lymphocytes and PBL had a similar pattern of reactivity, but the response was 2-100-fold greater in synovial fluid lymphocytes. We conclude that patients with prolonged Lyme arthritis have T cell responses to multiple spirochetal polypeptides. | |
| 2547538 | Autoantibodies to DNA topoisomerase II in cryptogenic fibrosing alveolitis and connective | 1989 May | Sera from patients with autoimmune lung and connective tissue diseases were investigated for antibodies to topoisomerase II. Anti-topoisomerase II antibodies were detected by ELISA in 37% of sera from patients with cryptogenic fibrosing alveolitis (CFA), in one (8%) case of sarcoidosis and in 31% of sera from systemic lupus erythematosus (SLE) patients. Sera from rheumatoid arthritis, juvenile rheumatoid arthritis, progressive systemic sclerosis, Sjögren's syndrome and undifferentiated connective tissue disease were negative. CFA and sarcoidosis sera strongly reacted in immunoblotting with a 170 kD protein, also recognized by rabbit antiserum to recombinant topoisomerase II, while SLE sera presented a weak reaction. Pre-adsorption with dsDNA dramatically decreased the topoisomerase II binding in ELISA by the most positive SLE serum, but did not affect the binding by the most positive CFA serum, thus indicating that anti-topoisomerase II reactivity of SLE sera is probably due either to cross-reacting antibodies or, in part, to minor DNA contamination of our enzyme preparation. The determination of DNA topoisomerase II relaxation activity, performed after incubation with antibody-positive sera, showed that only CFA sera precipitate enzymatic activity. The finding that CFA presents antibodies to an enzyme essential to cell survival stresses the role of autoimmunity in the pathogenesis of idiopathic pulmonary fibrosis. This may offer further insight into the cause of autoimmune disease and prove a valuable tool in the study of enzyme molecular biology. | |
| 2418139 | Polynucleotide antibodies in connective tissue disease: viral markers or disease mediators | 1986 Feb | Antibodies to polynucleotides are seen primarily in systemic lupus erythematosus (SLE), but also occur in a variety of other connective tissue diseases. We looked at the prevalence of antinucleotide antibodies (double- and single-stranded RNA and DNA [dRNA, sRNA, dDNA, and sDNA]) in the sera of patients with SLE (70), rheumatoid arthritis (RA) (31), juvenile rheumatoid arthritis (JRA) (68), osteoarthritis (12), and of 22 patients with a preceding viral illness. In comparison with sera from a control population, elevated mean antibody levels to sRNA were found in the sera of all the patients with connective tissue disease, as well as in the sera of patients with preceding RNA, but not DNA, viral infections. Elevated mean levels of antibodies to dRNA were seen in all groups with the exception of RA. Elevated mean antibody titers to sDNA were not seen in patients with JRA nor were they present in the sera of patients with preceding RNA viral infections. Elevated mean anti-dDNA titers were seen only in sera from patients with SLE. High correlation coefficients between the levels of antibodies to sRNA and dRNA in sera from SLE and RA, and between sDNA and dDNA in sera from SLE suggest cross-reactivity of the antibodies in these diseases. Immunization of an elderly population with influenza (RNA) viral vaccine induced antibodies to sRNA only. These studies further document the prevalence of antipolynucleotide antibodies in the sera of patients with connective tissue diseases.(ABSTRACT TRUNCATED AT 250 WORDS) | |
| 2141878 | Some predictors of radiographic alveolar bone height reduction over 6 years. | 1990 May | The present study was undertaken to 1) develop a model to predict the proportion of sites with alveolar bone height reduction over 6 years by means of a few factors, 2) build a second model to predict the initial values of the dependent variable, and 3) describe the relationship between initial bone loss and the bone loss over 6 yr with age. 142 subjects (18-67 yr) were examined radiographically at baseline and 6 yr later using a standardized method. For each subject, the proportion of sites depicting significant alveolar bone height reduction during the study was assessed. Explanatory variables were: presence of initial bone loss, local plaque retaining factors, age, sex, number of missing teeth at baseline and rheumatoid arthritis. Employing multiple regression analysis, the combined effect of initial bone loss, plaque retaining factors, age and rheumatoid arthritis provided the best model suited to predict the proportion of sites undergoing bone loss over time. However, age, plaque retaining factors and number of missing teeth were the best predictors of initial bone loss. A logistic regression model was then used to study the significance of these predictors at the site level. This model indicated that alveolar bone loss over time at a given site is related mainly to presence of local factors and initial bone loss at that site as compared to the effect of other sites with local factors and initial bone loss in the subject. Age demonstrated a linear relationship with initial bone loss and a curvilinear relationship to periodontal disease progression.(ABSTRACT TRUNCATED AT 250 WORDS) | |
| 3668846 | Influence of concomitant aspirin or prednisone on methotrexate synovial fluid concentratio | 1987 Oct | Methotrexate (MTX) is currently being used in the treatment of patients with rheumatoid arthritis. The purpose of this study was to investigate the effect of two classes of drugs, steroids and salicylates, on MTX synovial fluid concentrations. A novel canine model of monoarticular inflammation was used, in which each animal served as its own control with both inflamed and normal knees in the same animal. After the 6-week immunization process, animals in each group received either no drug (control), prednisone or aspirin (low dose and high dose) for 1 week before MTX. On the day of the study, each animal was given i.v. MTX, and serial serum and synovial fluid samples were obtained. Laboratory, histologic and clinical observations supported the presence of monoarticular inflammation. The end-of-infusion synovial MTX concentration in inflamed knees was significantly greater than in normal knees (P less than .05), but, 2 hr after the end of infusion, they were not different. The end-of-infusion ratio of synovial fluid MTX concentration to serum MTX concentration (both total and unbound) was significantly lower in the prednisone group than in the other treatment groups (P less than .05). The end-of-infusion ratio of the MTX synovial concentration in the inflamed knee compared with the normal knee at 2 hr was significantly lower in the prednisone group than in the other three treatment groups (P less than .05). These results have therapeutic implications for the use of MTX in treating rheumatoid arthritis. | |
| 1968678 | Arthritis in DBA/1 mice induced with passively transferred type II collagen immune serum. | 1990 Feb | Arthritis was induced in DBA/1 mice by passive transfer of syngeneic anti-type II collagen (CII) serum concentrate. After transfer of serum containing 0.2 or 0.5 mg anti-CII auto-antibodies the first clinical signs of arthritis appeared 48 h after injection. Severe clinical arthritis was detected 96 h after injection. Immunohistochemical analyses of joints 48 h after serum injection revealed synovial foci in intercarpal and metacarpophalangeal joints of macrophage-like cells, expressing C3bi-receptors and major histocompatibility complex class II molecules, and infiltration of few CD4+ lymphocytes. Later (96 h after injection), the inflamed synovia were dominated by C3bi-receptor+ polymorphonuclear cells. In contrast to conventionally induced collagen arthritis (CIA), the inflammatory infiltrates, filling joint spaces and synovial tissue, were extensively dominated by polymorphonuclear cells, whereas macrophage-like cells expressing class II molecules and a few T cells were seen only in the periphery of the developing pannus. The anti-CII serum induced arthritis may be used as a model for studies of humoral mediated mechanisms operating in conventionally induced CIA as well as in rheumatoid arthritis. | |
| 2671335 | Pneumatosis intestinalis in children beyond the neonatal period. | 1989 Aug | Pneumatosis intestinalis (PI) is a well-recognized manifestation of necrotizing enterocolitis (NEC) in the newborn--a condition that often requires surgical intervention for infarcted bowel. However, little information is available concerning PI in older children or its management. Sixteen older infants and children (greater than 2 months) had x-ray findings of PI (intramural air). There were eight girls and eight boys ranging in age from 2 months to 8 years. Associated conditions included short bowel syndrome (SBS) (8), congenital heart disease (2), iron ingestion (1), nesidioblastosis (1), hemolytic anemia (1), rheumatoid arthritis (1), bronchopulmonary dysplasia (BPD) (1), and malrotation (1). Clinical presentation included abdominal distension (13), bloody diarrhea (12), bilious emesis (5), and lethargy (5). Two patients on steroids had unsuspected PI identified as an incidental operative finding during pancreatectomy for nesidioblastosis (1) and splenectomy for hemolytic anemia (1), respectively. Only four other children (iron toxicity, postcardiac catheterization, rheumatoid arthritis, and BPD required surgical intervention. Each manifested peritioneal irritation, acidosis, and hypotension or had pneumoperitoneum on abdominal x-ray. In ten of 14 patients, PI was managed nonoperatively with nasogastric suction, fluid resuscitation, intravenous (IV) antibiotics (seven to ten days), and repeated abdominal x-ray and physical examinations. Children with SBS comprised 50% of the total number of patients and eight of ten treated by observation. All had associated viral syndromes (rotavirus) or rhotozyme-positive stools and developed bloody diarrhea. There were two deaths (12.5%) in patients with iron toxicity and congenital heart disease who required resection of gangrenous bowel. All of the other patients survived.(ABSTRACT TRUNCATED AT 250 WORDS) | |
| 2081787 | The use of monoclonal antibodies for treatment of autoimmune disease. | 1990 Nov | Over the past decade monoclonal antibodies have been successfully employed in a number of animal models of autoimmune disease. We have used antibodies to the class II gene products of the major histocompatibility complex, the CD4 molecule on helper T cells, and the T-cell receptor. Monoclonal anti-class II antibodies have been administered to treat paralytic disease in the animal model of multiple sclerosis--experimental allergic encephalomyelitis. These antibodies not only reverse acute paralytic disease but also decrease the number of relapses in a model of relapsing/remitting multiple sclerosis when given after the first attack. The advantage of this form of therapy is that it is haplotype specific. In other words, in a heterozygous individual it is possible to block the major histocompatibility gene associated with disease susceptibility while leaving other major histocompatibility gene products free for antigen presentation. Thus, animals given this form of immunotherapy are not significantly immunosuppressed. Antibodies to the CD4 molecule have been equally effective in treating animal models of autoimmunity. We and others have reversed ongoing paralysis in experimental autoimmune encephalomyelitis. Relapses have been diminished after the administration of anti-CD4. Antibodies to CD4 have been used successfully to treat animal models of systemic lupus erythematosus, rheumatoid arthritis and myasthenia gravis. Recent trials with anti-CD4 have been successful in the treatment of rheumatoid arthritis and cutaneous T-cell lymphoma. The latter trial employed a chimeric human/mouse antibody. Antibodies to the variable region of the T-cell receptor have been employed to treat experimental autoimmune encephalomyelitis.(ABSTRACT TRUNCATED AT 250 WORDS) | |
| 2303514 | Two-stage reimplantation for the salvage of total knee arthroplasty complicated by infecti | 1990 Feb | Thirty-eight total knee replacements (in thirty-five patients) that were complicated by infection were treated with a two-stage protocol for reimplantation. The clinical results in these knees (nine of which have been previously reported on) were evaluated at an average follow-up of four years (range, 2.5 to ten years). There was only one documented recurrence of infection with the original organism. Three patients in whom the immunological system was suppressed had a subsequent hematogenous infection with a different organism. According to the knee-rating system of The Hospital for Special Surgery, there were eleven excellent, thirteen good, six fair, and seven poor results. For one patient who had severe polyarticular rheumatoid arthritis, the result could not be rated. The results of this study suggested that the two-stage protocol for reimplantation, with a six-week interval of intravenous antibiotic therapy, is the procedure of choice for the treatment of an infection around a total knee arthroplasty. A patient who has polyarticular rheumatoid arthritis and in whom the immunological system is suppressed may not be an ideal candidate for the protocol. Gram-negative bacterial infection may be treated with this protocol, provided the organism is sensitive to relatively non-toxic antibiotic medication. | |
| 3150793 | Cytokines in chronic inflammatory synovitis. | 1988 | Cytokines likely play a role in the pathogenesis of rheumatoid arthritis and other chronic inflammatory arthritidies. Recent studies on the cytokine profile of inflammatory synovitis have provided insight into the mechanisms of cellular activation in the inflamed joint. Although gamma interferon has been proposed as a major macrophage activating factor and inducer of class II major histocompatibility antigens in the joint, studies using sensitive and specific immunoassays have shown that the concentration of this lymphokine in synovial fluid is probably not sufficient to account for the high level of HLA-DR expression on Type A synoviocytes and macrophages in the joint. In contrast, GM-CSF has recently been identified in synovial effusions of patients with rheumatoid arthritis and is produced by synovial tissue cells in vitro. Like gamma interferon, GM-CSF is a known macrophage activating factor and induces HLA-DR on cells of macrophage lineage. Furthermore, supernatants of cultured synovial tissue cells contain an HLA-DR inducing factor that is neutralized by specific antibodies to GM-CSF but not by antibodies to gamma interferon. These data suggest that GM-CSF plays a significant role in macrophage activation in the synovium. | |
| 2011600 | Protective effect of transforming growth factor beta 1 on experimental autoimmune diseases | 1991 Apr 1 | Interleukin 1 (IL-1) and tumor necrosis factor alpha are thought to contribute to the inflammatory response associated with autoimmune diseases. Transforming growth factor beta 1 (TGF-beta 1) counteracts many effects of these cytokines and has various immunosuppressive properties. In the present study, it is shown that microgram amounts of TGF-beta 1, injected daily for 1-2 weeks, protect against collagen-induced arthritis (CIA) and relapsing experimental allergic encephalomyelitis (REAE), the animal models for rheumatoid arthritis and multiple sclerosis, respectively. When administered during induction of the disease, TGF-beta 1 prevents CIA but only delays the onset of REAE by 2-3 days. However, when administered during a remission. TGF-beta 1 prevents the occurrence of relapses in REAE. The results suggest that TGF-beta 1 has powerful anti-inflammatory effects, mimicking in some respects the beneficial effects of immunosuppressive drugs in these experimental models of autoimmune disease, but without discernable adverse effects. | |
| 1764847 | Elevated IgA anti-gliadin antibodies in juvenile chronic arthritis. | 1991 Nov | Increased intestinal permeability secondary to treatment with non-steroidal anti-inflammatory drugs (NSAIDs) and raised levels of anti-gliadin antibodies (AGA) have been reported in adults with rheumatoid arthritis. We have therefore retrospectively investigated the presence of serum AGA of the IgA and IgG classes in 70 patients with juvenile chronic arthritis (JCA). Serum IgA (but not IgG) AGA were found to be higher in JCA patients than in controls (6.2 +/- 8.7 vs 2.1 +/- 1.5 AU/ml; p less than 0.0001). This finding was observed independently of the JCA onset subtype or disease activity; however, lower levels of IgA AGA were found in patients with pauciarticular JCA and in those in remission. No significant differences in IgA AGA serum levels were observed between untreated patients and patients treated with NSAIDs. Five patients who presented the highest levels of IgA AGA were further studied a second time; serum IgA AGA were found to be markedly reduced or normalized and no clinical or laboratory evidence of coexistent coeliac disease was observed. In conclusion, our results suggest that the elevation of IgA AGA seen in our patients is secondary to non-specific immune stimulation rather than to an NSAID-induced increase in intestinal permeability. | |
| 2663516 | Familial Mediterranean fever (recurrent hereditary polyserositis) in children: analysis of | 1989 Jun | The clinical profile, course and complications of familial Mediterranean fever (recurrent hereditary polyserositis) seen in 88 children over a period of 11 years are presented. Forty eight children (55%) started their illness below the age of 5 years, and the mean age of onset was 4.9 years. Peritonitis occurred in 85% of children, arthritis in 50%, pleuritis in 33% and erysipelas-like lesions in 16%. Two children developed renal amyloidosis, and one third of the children were subjected to unnecessary operative surgery, reflecting the diagnostic difficulties. The arthritis was mono-articular in 80% and polyarticular in 20% of children with arthritis, and was seronegative (rheumatoid factor and antinuclear antibodies). Human leucocyte antigen (HLA) typing for the B-27 antigen carried out in ten children with arthritis was negative. The synovial attack showed a wide variation in the clinical presentation, course and duration of arthritis, causing diagnostic difficulties. The difficulties in the differentiation of recurrent hereditary polyserositis (familial Mediterranean fever) arthritis from the common causes of acute and chronic juvenile arthritis and the seronegative spondyloarthropathies are discussed. Of 45 children treated with colchicine, 42 children (93%) achieved a therapeutic response. | |
| 3288324 | Neoplastic associations of rheumatic diseases and rheumatic manifestations of cancer. | 1988 May | Associations between rheumatic diseases and malignant neoplasms are still inferential and based largely on epidemiologic data. Rheumatoid arthritis predisposes weakly to the occurrence of lymphoreticular neoplasms. This is more clearly true of Sjögren's disease, whether or not it is associated with RA. A subset of DM/PM which becomes manifest in close temporal proximity to a neoplasm may be a paraneoplastic reaction, but DM/PM, in general, does not predispose to neoplasia. Scleroderma in its early phase is associated with the development of breast cancer in women, and after a decade or longer, if pulmonary fibrosis has developed, with lung cancer. Of the drugs that have been used to treat these diseases, cyclophosphamide is most strongly implicated as a carcinogenic agent, particularly inducing lymphoreticular neoplasms and carcinoma of the bladder. Musculoskeletal symptoms that may be clues to the existence of cancer may either be caused by invasion of the neoplasm or be mediated by unidentified neurohumoral mechanisms. Except for multiple myeloma, primary neoplasms of skeletal tissues tend to occur under the age of 50 years. Metastatic disease occurs congruently with the age incidence of the primary neoplasm. Metastases may mimic mono- or oligoarticular arthritis if they happen to be periarticular or synovial. These metastases result most often from carcinoma of the lung or, in women, carcinoma of the breast. Hypertrophic pulmonary osteoarthropathy usually is due to carcinomas of the lung other than the small cell variety, and infrequently from other intrathoracic primary or secondary neoplasms. RA may be mimicked. Both skeletal metastases and HPOA are detected with greater sensitivity, but not specificity, by isotopic scanning techniques than by radiography. Of the other paraneoplastic musculoskeletal syndromes, neuromyopathy is the most frequent. It must be distinguished from cachexia, polymyositis, polymyalgia rheumatica, and the myasthenic syndrome. Both neuromyopathy and Eaton-Lambert (myasthenic) syndrome are predominantly associated with small cell carcinoma of the lung and both are best diagnosed by electromyography. Carcinomatous polyarthritis and the palmar fasciitis-arthritis syndrome occur with various neoplasms, although the latter appears to be particularly associated with ovarian carcinomas. The paraneoplastic arthritides test negatively for the rheumatoid factor, but no reliable positive immunochemical clues have as yet been identified. | |
| 2201199 | Immunotherapy of collagen-induced arthritis by a T-cell antiproliferative molecule. | 1990 Aug | The present study describes a novel experimental immunotherapeutic methodology for the reduction of inflammatory synovitis that is noted in an animal model of rheumatoid arthritis. The reduction in inflammation is noted in the animals administered a contra-interleukin-2 (IL-2) cytokine secreted by a cloned T-cell line. The mechanism of reduction of inflammation by this cytokine is through the inhibition of activation and differentiation of T lymphocytes. The cytokine inhibits the in vitro mitogen activation of T-cell lymphocytes as well as antigen-specific activation of a collagen type II specific T-cell line. In addition, decreased levels of messenger RNA coding for interleukin-2 are noted in T lymphocytes and IL-2 activation of the collagen type II specific cell line is inhibited by the contra-IL-2 cytokine. This initial description of a reduction in inflammation by a contra-IL-2 lymphokine suggests that immunoregulatory biologic molecules that are antagonists to IL-2 may be useful for the experimental immunotherapy of cartilage connective tissue pathology. | |
| 2697951 | [The effect of dimethyl sulfoxide on the thromboelastographic indices and the microcircula | 1989 | Using a blind method for assessing the results, a study was made of the effect of dimethylsulfoxide (DMSO) on fibrin formation and microcirculation in 42 patients with rheumatic diseases (rheumatoid arthritis, systemic scleroderma, Raynaud's syndrome). It has been shown that the therapeutic effect of DMSO in rheumatic diseases is determined to a definite degree by its normalizing action on fibrin formation and microcirculation. | |
| 2535630 | Silicone lymphadenopathy with concomitant malignant lymphoma. | 1989 Nov | Six cases of axillary lymphadenopathy induced by silicone elastomer following silastic finger joint arthroplasty have been reported; 2 cases had associated malignant lymphoma. This is the 3rd reported case of malignant lymphoma with concomitant silicone lymphadenopathy discovered 8 years after insertion of silastic finger joint arthroplasty for longstanding rheumatoid arthritis. Histology revealed a partially replaced reactive lymph node with immunoblastic lymphoma. Both sides contained single and clusters of multinucleated giant cells with silastic particles, as well as formed asteroid bodies. Malignant lymphoma is associated with rheumatoid disease, but to date, silicone particles have not been linked to malignant lymphoma. | |
| 3769251 | Significance of operative cultures in total hip arthroplasty. | 1986 Oct | The significance of operative cultures to the development of deep infections in total hip arthroplasties performed for failures of previous surgeries was studied. Four hundred fifty conversion total hips were followed for three or more years. Twenty-nine percent had had more than one prior surgery. One hundred twenty-one organisms in 81 hips (18%) were found. Gram-positive cultures were increased in rheumatoid arthritis. Twenty (4.4%) of the hips became infected. Nine (11%) of the hips with positive cultures and 11 (3%) of the hips with no growth at conversion later developed infections. Failed total hip arthroplasties with a positive culture had a 40% rate of reinfection. Rheumatoid hips had a two-times higher infection rate, and 80% were caused by gram-negative organisms. Hips with a gram-negative growth at the time of conversion had a higher infection rate than hips infected with gram-positive organisms. | |
| 2585906 | [A case of adult Still's disease with severe pulmonary complications]. | 1989 Sep | We reported a case of adult Still's disease accompanied by pericarditis, pleuritis and extensive pneumonitis with respiratory failure. A 59-year-old woman was admitted to our hospital because of high grade fever and sore throat. She had a spiking fever between 38 degrees C and 40 degrees C. Surface lymph nodes were palpable in the neck and inguinal lesions and hepatosplenomegaly was recognized. Laboratory data showed a marked increase in peripheral leukocytes, erythrocyte sedimentation rate, liver dysfunction and anemia. Serologic tests were negative for various autoantibodies and rheumatoid factor. She received various antibiotics, but there was no improvement. Later, a rheumatoid rash which suggested adult Still's disease developed. The diagnosis of adult Still's disease was made by skin biopsy and clinical course. Although pericarditis, pleuritis and extensive pneumonitis were accompanied with severe respiratory failure, her symptoms improved with steroid pulse-therapy. A transbronchial lung biopsy revealed moderate fibrosis and cell infiltration in alveoli. |