Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
126639 Use of the reversed passive Arthus reaction as a test for anti-inflammatory agents. 1975 Feb The immune complex-induced reversed passive Arthus (RPA) reaction in the rabbit has been investigated as a screening test for detecting anti-inflammatory agents potentially more effective in the treatment of rheumatoid arthritis than those presently available. RPA lesions, characterized by edema, erythema, and hemorrhage, were elicited by intravenous injections of bovine serum albumin (BSA) followed by intradermal injections of rabbit anti-BSA antiserum. The anti-edema activities of compounds (mg quantities required for testing) were evaluated after their administration by the intradermal route (compounds admixed with antiserum) as well as by the intraperitoneal route. Of 14 reference anti-inflammatory agents tested by the intradermal screening procedure, only aurothioglucose and chloroquine were inactive. Other pharmacologically active compounds (e.g. antihistamines, anti-complement agents, cytotoxic-immunosuppressives) were also evaluated after their intradermal administration. Protoporphyrin, phloretin, and hexadimethrine bromide (Polybrene) were active. When whole antiserum, or the antibody fraction of the serum, was used to eliminate nonspecific edema, intraperitoneally administered reference agents were found to be effective in the RPA test.
2935580 Effects of Wy-18,251 (3-p-chlorophenyl)thiazolo[3,2-a]benzimidazole- 2-acetic acid), levam 1985 In vitro culture of normal BALB/c spleen cells with staphylococcal enterotoxin B (SEB) activates antigen non-specific suppressor T cells (Ts) which can be assayed by their ability to suppress antibody production in a plaque assay. Addition of the experimental immunomodulatory drug Wy-18,251 (10-100 microM) to cultures of spleen cells plus SEB significantly increased Ts activity relative to cultures without the drug. Similar results were obtained with levamisole, but, in contrast, indomethacin (0.1-10 microM) inhibited SEB-induced suppressor cell activity. The ability of Wy-18,251 to augment Ts activity could be therapeutically useful in the treatment of those autoimmune diseases, such as rheumatoid arthritis and systemic lupus erythematosus, in which hyperactive B cell function is a characteristic feature.
6363709 Cold reacting antinuclear antibody in Henoch-Schönlein Purpura. 1983 Nov Although the etiology is unknown, a number of features of Henoch-Schönlein Purpura (HSP) suggest an immune pathogenesis. Using indirect immunofluorescence, we evaluated 19 patients with HSP for the presence of cold reacting antinuclear antibody (ANA). Eighteen of 19 patients demonstrated cold reacting ANA of the IgG class when human epithelial cells were utilized as substrate. The immunofluorescent pattern was speckled in all. One patient demonstrated ANA when tested at room temperature, while the remaining 18 were negative at room temperature. Cold reacting ANA persisted for periods of 6 months to 6 years in 10 patients, regardless of concomitant disease activity. None of the HSP patients demonstrated cold reacting ANA when mouse kidney sections were employed as substrate. Moreover, none demonstrated antibody to DNA or to extractable nuclear antigen. Sera from 20 normal adults, 10 normal children, and 7 children with juvenile rheumatoid arthritis were all negative when tested for cold reacting ANA. Cold incubation altered neither the ANA titer nor the immunofluorescent pattern in 5 patients with systemic lupus erythematosus. These results indicate that patients with HSP elaborate a cold reacting ANA which is substrate dependent.
7060332 Oxaprozin disposition in renal disease. 1982 Apr Effects of renal disease on the disposition kinetics of oxaprozin, a nonsteroidal antiinflammatory analgesic, were assessed in 15 subjects who were normal, renally impaired, or who had been undergoing hemodialysis. Oral dose clearance (Cloral), volume of distribution at steady-state (V88d), and elimination half-life (t 1/2) did not substantially differ among the three groups. Mean fraction unbound oxaprozin in plasma (fup) increased from 0.08% in the normal group to 0.18% and 0.28% in the two azotemic groups. Consequently, unbound drug kinetic parameters, including intrinsic clearance (Clint) and V88du of unbound drug were reduced from 2.9 l/hr/kg and 193 l/kg in normal subjects to approximately 1.6 l/hr/kg and 91 l/kg in azotemic patients. The smaller volume of distribution is consistent with a decrease in oxaprozin tissue binding in azotemia. The decreased plasma and tissue binding and lower Clint suggest that, in the treatment of azotemic patients with rheumatoid arthritis, the dose of oxaprozin should begin at 600 mg once a day.
6978519 Purification and characterization of a nuclear SS-B antigen. 1982 Jan A nuclear SS-B antigen was isolated from a saline extract of acetone powder of rabbit thymus by precipitation with ammonium sulphate, affinity chromatography with Blue Sepharose CL-6B, and preparative agarose gel electrophoresis. The mol. wt of the antigen was 68,000. Its electrophoretic mobility was similar to that of pre-albumin, and the iso-electric point was around pH 4.0. The main amino acids of the antigen were glutamic acid, leucine, lysine and alanine. Both histidine and tyrosine were also found. The purified antigen precipitated with anti-SS-B sera but not with any other reference antisera. It resembled La and Ha antigens in susceptibility to proteolytic and nucleolytic enzymes and to heat. The purified SS-B antigen, however, had a higher molecular weight than did the Ha and La antigens. The molecule could not be split into subunits with mercaptoethanol or acid. Counter-electrophoresis showed antibodies to the SS-B antigen in sera from patients with rheumatic diseases, including rheumatoid arthritis, systemic lupus erythematosus and Sjögren's syndrome, but not in amy of the control sera.
6754627 Detection of basophil sensitization by IgE antibodies to nuclear antigens in connective ti 1982 Responses of the IgE type to various nuclear antigens have been explored using the human basophil degranulation test (HBDT) to single (SS) and double-stranded (DS) deoxyribonucleic acid (DNA), nuclear ribonucleoprotein (nRNP), and Sm antigens. This study was conducted on systemic lupus erythematosus (SLE) patients as compared to rheumatoid arthritis (RA) polymyositis (PM), scleroderma (SCL) and mixed connective tissue disease (MCTD). SLE and MCTD patients showed a high level of basophil degranulation to the four antigens. Degranulation to nRNP protein was higher in MCTD than in SLE cases. HBDT to the four antigens were constantly negative in control donors and in RA, PM and SCL. Basophil degranulation to DS-DNA in SLE was blocked by previous exposure of the blood to anti-human-IgE antiserum. These results exemplify the specificity of the HBDT, making this simple and fast test a useful tool in the diagnosis of connective tissue diseases.
6458701 Immunosuppressive effects of deflazacort - a new glucocorticoid with bone-sparing and carb 1981 Sep Deflazacort is a synthetic glucocorticoid with fewer adverse effects on bone and carbohydrate metabolism than prednisone or beta-methasone. Its antiinflammatory effects have compared favorably to prednisone in European studies of rheumatoid arthritis. We compared the immune effects of prednisone and deflazacort in normal volunteers. Circulating lymphocytes were reduced similarly by equivalent doses of both drugs; monocyte numbers were reduced more by deflazacort. Each drug suppressed autologous mixed lymphocyte reaction in vitro and in vivo; this effect persisted longer with deflazacort. Deflazacort may be a superior therapeutic agent because of its lower toxicity and longer duration of one immunosuppressive effect; it might be effective in alternate day regimens.
310883 Antibody to extractable nuclear antigen in the rheumatic diseases. 1978 Winter Two hundred and eighty-four patients with various rheumatic diseases were studied for the prevalence of antibodies to extractable nuclear antigen (anti-ENA) using an improved haemagglutination technique. Anti-ENA rarely occurred in patients with rheumatoid arthritis, scleroderma, polymyositis, dermatomyositis and Sjögren's syndrome. Seventeen per cent (13/72) of patients fulfilling at least four preliminary ARA criteria for systemic lupus erythematosus (SLE) demonstrated anti-ENA. The predominant antibody was directed at ribo-nuclease-resistant ENA (anti-Sm). Antibodies to ribo-nuclease-sensitive ENA (anti-RNP) occurred in the minority of patients with SLE (2/72) and the mixed connective tissue disease syndrome (MCTD). A trend toward an increased incidence of renal disease in SLE patients with anti-Sm was present. Sequential analysis of anti-Sm in patients with SLE showed a fall in titre paralleling the normalization of anti-DNA antibody titres and serum complement values. No case of unrecognized MCTD was uncovered in our rheumatic disease population.
136874 Immunogenetic aspects of allotransplantation. 1976 It now appears unequivocal that three markers exist in a linkage group in chromosome 6 of man: HLA-A, HLA-B and PGM3 (Fig. 1.) Tentatively, two other HLA loci and one Ir gene have been mapped close to HLA-B. The probable map order is HLA-A - HLA-C - HLA-B - HLA-D - Ir. The biological functions of these loci are unknown. However, HLA-A, B and C are important in allograft rejection. Other closely linked loci (HDR, CML) appear to be important in the first events of the allograft rejection (first set) and in generation of killer cells. HLA-D might be important in cellular recognition and graft-versus-host reactions (matching at HLA-D decreases the incidence and severity of graft-versus-host disease), and the Ir genes in the defense against infections. HLA-B and HLA-D loci are important markers in studies of disease susceptibility. HLA-B locus antigens HLA-B27 and HLA-B8 are frequently associated with arthritic or autoimmune disorders. HLA-D determinants have been found in association with multiple sclerosis and C2 deficiency (HLA-DW2); juvenile diabetes and Addison's disease (HLA-DW3) and adult type of rheumatoid arthritis (HLA-DW4).
12309933 Mexican plants and human fertility. 1979 Jul
6437730 A comparative study of glucose oxidase versus FITC-labeled antibody techniques for the det 1984 Sera from 98 patients were examined for antinuclear antibodies (ANA). The patient population has been previously identified clinically as having the following diseases: systemic lupus erythematosus, scleroderma, dermato or polymyositis, discoid lupus, rheumatoid arthritis, Raynaud phenomena only, undifferentiated connective tissue disease, and psoriasis. All sera samples were tested using both HEp-2 cells and rat kidney tissue as substrates and were stained with both fluorescein-conjugated antihuman antibody and glucose oxidase-conjugated antibody to human IgG. Each serum was initially tested at a screening dilution of 1:40 with PBS. Positive sera were serially diluted until an end point was observed. The number of dilutions for each specimen in all four combinations was compared mathematically using the Pearson product moment correlation. Using this method, glucose oxidase- and fluorescein-conjugated antinuclear antibody (FANA) techniques appear to have a high positive correlation (r = 0.92 kidney, r = 0.95 Hep-2) in this patient population. In our experience, the glucose oxidase technique offers comparable results to FANA and is ideally suited for the hospital laboratory, especially facilities without the benefit of a fluorescent microscope.
6871584 Clinical features of early cases of systemic lupus erythematosus in Iraqui patients. 1983 Aug The clinical features of early cases of systemic lupus erythematosus (SLE) in 67 (55 female and 12 male) patients are reported in a prospective study and its prevalence rate is calculated. The disease accounted for 0.67% of all medical admissions and it was the third most frequent inflammatory rheumatic disease. By comparison with rheumatoid arthritis and extrapolation of the data, the prevalence of SLE was one case per 1867 of the population, one per 1127 of the total female population and for women aged between 10 and 49 years it was one per 616. Multisystem involvement was noted in all patients. Our results were presented and compared with other studies. Significant differences between our study and others were noted with respect to alopoecia, mouth ulcers, pericarditis and pleurisy. Subclinical involvement of the liver was noted in 26% and of the lungs in 19%. Hepatomegaly was noted twice as often in younger compared with older patients. SLE is a disease with an apparently increasing prevalence in Iraq. There is a need for a greater awareness on the part of practising physicians and more widespread availability of sensitive laboratory tests for diagnosis of the disease.
6681132 The retention and distribution in the rabbit knee of a radionuclide complexed with a lipop 1983 Apr The application of radiosynovectomy to patients with rheumatoid arthritis has been severely restricted by the difficulty of preventing leakage of the radioisotope from the joint cavity. We have synthesised a lipophilic chelator, 3-cholesteryl 6-[N'-iminobis(ethylenenitrilo)-tetraacetic acid]hexyl ether (Chol-DTTA) which can complex with a variety of beta-emitting radionuclides and is incorporated into the lipid phase of liposomes. The retention in the synovial cavities of rabbit knees of liposomes containing Chol-DTTA, complexed with the gamma-emitting tracer 51Cr, has been measured over a period of 21 days and compared with colloidal and water-soluble preparations. The distribution of the radionuclide between the tissues of the joint was also examined. Results show retention of 51Cr delivered in chelator liposomes to be greater than 99% after 24 h. At this time, over 93% of the radioactivity had become associated with the synovium. We conclude that chelator liposomes offer considerable promise as vehicles for radioisotopes in radiosynovectomy.
6977559 Comparative tissue absorption of oral 14C-aspirin and topical triethanolamine 14C-salicyla 1982 Jan The local, articular, and systemic absorption of oral and topical salicylates was studied in dogs and humans using radioisotope techniques. Topical triethanolamine 14C-salicylate was found capable of percutaneous absorption into the knee joint and surrounding tissues. In dogs, topical salicylate application resulted in higher salicylate concentrations than oral aspirin in a number of tissues, despite lower blood levels. In patients with rheumatoid arthritis, intraarticular 14C-salicylate levels after triethanolamine 14C-salicylate cream were 60 per cent of those obtained with oral aspirin. Four of six patients reported equal improvement in local discomfort after oral and topical salicylates. A potential role for topical salicylate cream in the treatment of localized rheumatic disorders is suggested.
6972970 Alterations in T gamma cells in patients with chronic idiopathic thrombocytopenic purpura. 1981 Aug The number and percentage of T cells bearing Fc gamma receptors (T gamma) was quantitated in peripheral blood of patients with the autoimmune disease chronic ITP. In over half the patients, low initial percentages were obtained, the great majority of which returned to within the normal range after incubation under capping conditions. The phenomenon could be reproduced by pretreating normal T cells with immune complex containing sera or aggregated HGG. Furthermore, a reversible reduction in T gamma cells was observed in control patients with nonimmune thrombocytopenia and in pregnancy. In each case an association was observed between the reduced T gamma cell levels and the presence of circulating immune complexes, which suggested that the results could be explained by masking of Fc gamma receptors with preformed IgG-containing complexes. By contrast, patients with other autoimmune diseases such as scleroderma and rheumatoid arthritis had high or normal numbers of T gamma cells, respectively. Taken together, the findings do not support the existence of a gross deficiency of suppressor cells in patients with autoimmune disease and emphasize the need for caution in selection of markers for identification of T cell subsets.
6975376 Mixed connective tissue disease - a subset with sequential clinical and laboratory feature 1981 Jul Twenty-three patients who lacked the full picture of mixed connective tissue disease (MCTD) initially, developed new findings or experienced regression of initial features with time. Each patient had at least 1 extractable nuclear antigen (ENA) antibody titer greater than or equal to 1:10,000 composed exclusively of ribonucleoprotein; but variation in titer occurred in 9 and Sm antibody was transiently found in 3 patients. Four initially had other diagnoses and negative antinuclear antibody tests (ANA) before developing speckled ANAs. Eleven patients had consistently speckled ANAs. As suggested by earlier clinical observations, MCTD can change clinically and serologically. This study demonstrates the sequential development of the features of SLE, polymyositis, rheumatoid arthritis and in addition emphasizes the serologic studies may also vary over time in these patients.
6796481 [Studies of D-penicillamine (4) : effects on antibody formation (author's transl)]. 1981 Jul The value of D-penicillamine (D-PA) in the treatment of rheumatoid arthritis is now well established, however, the mode of action remains obscure. We studied the effects of D-PA on the primary and secondary homocytotropic antibody formation with various doses, timing, quantity of antigen stimuli and stress loading in mice. Homocytotropic antibody was assayed by rat PCA (IgE) or mouse PCA (IgG1), and the effects were compared with those of the other antirheumatic drugs such as aurothiomalate and chloroquine diphosphate and the immunosuppressive agents such as hydrocortisone and cyclophosphamide. The antibody formation was slightly suppressed by D-PA under various conditions induced by different quantities of antigen stimuli, while the effects of the other antirheumatic drugs and the immunosuppressive agents on the primary and secondary responses differed from that of D-PA. Stress loading applied with oral consecutive administration of saline for 3 weeks or by restraint with adhesive plaster from 3 days before the primary immunization reduced the antibody formation. D-PA restored the reduced IgE antibody formation after the secondary immunization and also weight of the spleen. These observations suggest that D-PA acts as an immunomodulating agent as the spleen weight and IgE antibody formation were recovered under conditions of induced stress.
7279820 Pattern of renal amyloidosis in Indian patients. 1981 Jan Two hundred and thirty-three patients with renal amyloidosis were studied in an attempt to identify the incidence and pattern of the disease in northern India. The incidence of amyloidosis was 1.01% of 6431 post-mortems and 8.4% of 1980 renal biopsies from patients who presented with clinical evidence of glomerular disease. Two hundred and three patients (87.1%) had secondary amyloidosis, 22 (9.4%) had primary amyloid and 8 patients (3.5%) had amyloidosis associated with multiple myeloma. Tuberculosis of various organs was the commonest predisposing disease accounting for 59.1% of secondary amyloidosis, followed by chronic suppurative lung disease in 24.1%. Rheumatoid arthritis, chronic osteomyelitis and lepromatous leprosy were seen in a small percentage of patients (2 to 8%). Proteinuria of varying degree was present in all the 233 patients and 12.9% of them had a daily protein excretion of more than 10 g. Post-mortem examination of 65 patients with renal amyloidosis showed that 75.3% also had amyloid deposit in the spleen, 63% in the liver, and 50.8% in the adrenals. Clinical evidence of disappearance of proteinuria was observed in 3 patients with secondary amyloidosis; in 2 of them, the regression of amyloidosis was confirmed by serial renal biopsy performed 3 and 5 years after the initial diagnosis.
6967943 Two types of Ia-positive T cells. Synthesis and exchange of Ia antigens. 1980 Aug 1 Two distinct types of Ia-positive T cells have been described. One type represents a blastoid T cell responding from stimulation by mitogens, antigens, and in allogeneic and autologous mixed lymphocyte culture reactions. This is a large cell that is strongly positive for Ia antigens as measured by a variety of different antisera. The other general type is a smaller cell with a lower expression of Ia antigens that is found at low levels in normal peripheral blood and is markedly elevated in various pathological states. It also rises rapidly after inoculation with tetanus toxoid and PPD in sensitized individuals. This cell does not incorporate thymidine and is enriched in the Tgamma fraction; it can be markedly concentrated from normal lymphocytes, and current evidence indicates that it is a T cell. The marked elevation of this cell in the blood of patients with rheumatoid arthritis is of special interest. Considerable evidence indicates that, at least in certain instances, the Ia antigens are synthetized by the cells that carry them. Incorporation of labeled amino acid experiments and the in vitro translation results presented above indicate this. However, the ready exchange of Ia antigens between cells in the experiments described indicates that uptake from other cells may be a significant source.
501898 Escape from sodium and potassium retaining actions of aspirin-like drugs used in a patient 1979 Aug Escape from sodium and potassium retaining actions of aspirin-like drugs used in a patient with Bartter's syndrome. An analysis was done with regard to the mode of escapes from sodium and potassium retaining actions of aspirin-like drugs in a patient with Bartter's syndrome. In the indomethacin therapy of the syndrome, there was a delay in the initiation of potassium escape as compared to sodium escape, whereas no delay was seen in the ibuprofen therapy. This delay was probably related to the direct or indirect inhibition of sodium-potassium exchange in the distal nephrons. The course of aspirin therapy went midway between the above two. In the spironolactone therapy, the mode of escape was a mirror image of the one in the indomethacin therapy. Also, in a patient with rheumatoid arthritis, but without Bartter's syndrome, the escapes from the effects of indomethacin were seen. In order to understand the effect of these drugs on potassium excretion in Bartter's syndrome, some other intrarenal events, such as the influence on chloride transport in the loop of Henle leading to potassium conservation, may have to be considered.