Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
ID | PMID | Title | PublicationDate | abstract |
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7100807 | [Study of antihistone and anti-bicatenary RNA antibodies in connective tissue diseases usi | 1982 Apr | Use of an immunoenzyme technique to seek two types of antibody (AB): antihistones and bicatenary anti-RNA, led to study of their distribution in different connective tissue and autoimmune diseases. Total antihistone AB and the H1 and H2b antifractions were seen almost exclusively in lupus (52.5 per cent of cases), principally during active phases of the disease since 87 per cent of active forms had antihistone AB as against 15 per cent of inactive forms. Antihistone AB would thus appear to be a valuable laboratory investigation in the diagnosis and surveillance of lupus. Bicatenary anti-RNA AB were more widely distributed, being found in DLE, RA, scleroderma and in various disorders with antinuclear antibodies. However they were slightly more common in active forms of lupus and their titres appeared to fall more quickly than those of antinuclear AB and anti-DNA AB at the time of clinical improvements. In RA, bicatenary anti-RNA AB were more commonly associated with inflammatory and progressive forms but further studies involving larger populations would be necessary to confirm these findings. | |
6335421 | The detection of circulating immune complexes containing C1q and IgG using a new rapid ser | 1984 | An ELISA sandwich assay for detecting circulating immune complexes (CIC) was evaluated. Heat-aggregated IgG (HAG) containing Clq (HAG:Clq) is used to generate standard curves for quantitation of CIC. Sera from 488 normal donors had an means of 3.8 +/- 15.3 micrograms/ml HAG eq and 97.1% had concentrations less than 35 micrograms/ml HAG eq (2 SD greater than means) and were considered negative. Sera from rheumatoid arthritis (RA) patients in active disease tested 86% positive for CIC (means = 104.5 +/- 63.4 micrograms/ml HAG eq) while 100% with inactive disease were negative (means = 11.4 +/- 3.7 micrograms/ml HAG eq). Similarly, in systemic lupus erythematosus (SLE) patients with active disease, 100% were positive (means = 133.1 +/- 50.6 micrograms/ml HAG eq) while 80% with inactive disease were negative (means = 20.4 +/- 21.4 micrograms/ml HAG eq). In AIDS (AIDS related), 88.5% of AIDS sera and 77.1% of lymphadenopathy syndrome (LAS) sera had elevated CIC. Sera from asymptomatic homosexual controls showed 85% positive for CIC. The serum ELISA test for CIC compared favorably with the 125I-staphylococcus binding assay but was more sensitive than the 125I-C1qBA. The OKT4/OKT8 ratios were also significantly reduced in AIDS and LAS. | |
6976376 | Synovial fluid lymphocytes differ from peripheral blood lymphocytes in patients with rheum | 1982 Jan | Peripheral blood (PBL) and synovial fluid lymphocytes (SFL) from 12 patients with rheumatoid arthritis (RA) were analyzed using monoclonal antibodies that detect specific T cell surface antigens (OKT3, OKT4, OKT8, SC1) and antigens associated with lymphocyte activation (anti-Ia, OKT10, B3/25). RA patients' PBL contained 1010 +/- 74 OKT4+ and 401 +/- 62 OKT8+ cells/mm3 (ratio OKT4+/OKT8+ = 2.4 +/- 0.3). In contrast, SFL from these patients exhibited a significantly different proportion of T cell subsets (ratio OKT4+/OKT8+ = 1.1 +/- 0.5) (p less than 0.0001) with 630 +/- 180 OKT4+ and 595 +/- 225 OKT8+ cells/mm3. Synovial fluid contained significantly more activated T cells based on the presence of Ia-positive T cells (19 +/- 5%) and reactivity with antibody OKT10 (49 +/- 7%) compared with RA-PBL (8 +/- 3% Ia-positive T cells and 13 +/- 6% OKT10+). Compared with RA-PBL, normal PBL contained an elevated number of OKT8+ cells (610 +/- 48/mm3), a similar number of OKT4+ cells (1040 +/- 86/mm3), and a lower percentage of activated lymphocytes (3 +/- 2% Ia-positive T cells and 10 +/- 8% OKT10+ cells). SFL, RA-PBL, and normal PBL all showed less than 3% cells reactive with antibody B3/25 (anti-transferrin receptor antibody), a marker found on in vitro activated T cells. These findings demonstrate that the lymphocytes at the site of inflammation differ significantly from the lymphocytes present in the peripheral blood of the same patients. RA patients had a small but significant decrease in the number of OKT8+ cells/mm3 compared with normal PBL (p less than 0.01), suggesting that this lymphocyte subset may home to synovial tissues, where it becomes activated. | |
1086990 | [Endoscopic study on the gastric tolerance of antalgic-antirheumatic substances:parsalmide | 1976 Oct 31 | The gastric tolerance of parsalmide, a new analgesic, antirheumatic and sedative substance was tested on a group of 50 arthrorheumatic patients with the purpose of assessing gastric damage if any. It was also compared with the tolerance of the better known antitrheumatic drugs in current use. The study was conducted with the endoscopic method, parsalmide being administered in quantities of 600 mg/die per os, broken up into 3 doses, for a period of 20 days. Unlike phenylbutazone, indomethacin and cortisone, parsalmide showed no ulcerogenous effect nor haemorrhage type alterations at gastroduodenal level, at least in the cases treated. Furthermore, the slight surface oedematous gastropathies that appeared during the research were not important enough to demand suspension of the treatment. Endoscopically this picture can be judged of little clinical importance (as with the majority of well known analgesic-antirheumatic drugs) and its incidence came within the mean. A fair tranquillizing action, detectable in the particularly amenable behaviour of the subjects undergoing endoscopy, is also worth reporting. | |
175396 | The arthropathy of hemochromatosis. | 1976 Mar | Five cases of hemochromatosis arthropathy are presented and the distinctive radiological features of the disease are described. Although the condition is typically degenerative, showing subchondral cyst formation, sclerosis, and thinning of cartilage, its distribution is characteristic. Selective degenerative changes of the second and third metacarpophalangeal joints are striking, particularly in the hands, while abnormalities in the intercarpal joints are variable and the interphalangeal joints are spared. Chondrocalcinosis involving both fibrous and hyaline cartilage is frequently seen as well, particularly in the large joints. The calcification is due to deposition of calcium pyrophosphate crystals, perhaps resulting from iron inhibition of pyrophosphatase. | |
1123459 | Kinetics of salicylates in blood and joint fluid. | 1975 Feb | Samples of blood and joint fluid from 30 patients who had taken acetylsalicylic acid were examined for concentrations of total salicylates. The data were arranged in groups according to diagnosis of the joint disease. Analysis of the data did not show significant differences in the kinetics of total salicylates into blood. In groups, the time to first appearance of 0.3 mg/liter averaged 6 minutes, and levels "close to maximum" concentration averaged about 23.0 mg/liter. Time to first appearance of 0.3 mg/liter of total salicylates in joint lfuid ranged from 10 to 31 minutes. The average level of maximum concentration of total salicylates in joint fluid was 14.8 mg/liter. Transport of total salicylates from blood to joint fluid showed a pattern consistent with the type of joint disease. Support was found for the hypothesis that diffusion was the major factor in the process of movement of total salicylates from blood to joint fluid. The histopathologic changes in different types of synovitis influenced the biophysical properties of the inner part of the joint capsule. | |
7026114 | The use of birth control pills in women with medical disorders. | 1981 Sep | Since little absolute data exist in the form of large prospective studies in patients with specific illnesses who are on oral contraceptives, the clinician must rely on well-founded empiric decisions in prescribing the pill for these patients. The decision should be based on a firm understanding of the pathophysiology and laboratory effects of the oral contraceptives. This must be juxtaposed with an understanding of the efficacy and effects of the estrogen and progestational components of the birth control pill and their interactions with maintenance medications. In the final analysis, though, the clinician must rely on a trial and error method in treating these patients. It must be stressed, however, that these women require careful monitoring, both clinically and biochemically. It is comforting to note that in all diseases studied to date, the use of birth control pills has not precipitated a catastrophic change. | |
806958 | [Lymphocytic subpopulations implicated in the rheumatoid rosette phenomenon]. | 1975 May | The significance of the phenomenon of rheumatoid rosettes (RR) was studied in 21 subjects suffering from rheumatoid polyarthritis (RP) and in 16 controls. Certain technical factors influenced the prevalence of RR. Thus the number of RR increased in the RP patients and the controls with increase in the number of sensitized 0 Rhesus - red corpuscules; nevertheless there was a significant difference between the results obtained with the RP patients and the controls. The length of incubation and the temperature played an important role: prolonged contact times (30 min to one night), particularly at 4C considerably increased the numbers of RR, which reached 10 per cent both, in the controls and in the RP patients. The separation of lymphocytes by filtration through nylon according to Greaves' technique was followed by a study of the T cells (E rosettes), the B cells (surface immunoglobulins), and the RR. In all cases (RP and controls), the numbers of RR increased after filtration through nylon which retained the B cells. Separation of the lymphocytes by the centrifuging of the E rosettes showed that the proportion of RR was clearly higher in a population rich in B lymphocytes and lower in a population rich in T lymphocytes. Futhermore, filtration through nylon of cell suspensions rich in B lymphocytes showed a considerable rise in the RR and parallel drop in the number of B cells. Reduction of the RR by centrifuging did not affect the numbers of T or B cells. In the light of these results, it seems that the cell responsible for the formation of the RR does not have the characteristics of either the T or the B lymphocytes: a lymphocyte carring a receptor for the fragment Fc of the immunoglobulins (K cells) could be involved. In this case, the RR should be related to the EA rosettes of which they perhaps represent and active fraction. | |
48497 | Interaction of the hinge region of human immunoglobulin G with a murine lymphocyte membran | 1975 May | Evidence is presented which indicates the presence on murine lymphocytes of a membrane receptor for determinants on the hinge region of human IgG. These determinants are exposed following pepsin scission of IgG molecule, i.e. on the F(ab')2 fragment. The evidence for a hinge receptor derives, in vivo, from splenic localization of F(ab')2 in germinal centres and, in vitro, from immunofluorescent binding studies. The sequential immunofluorescent pattern for the uptake of human F(ab)2 fragments into murine spleen germinal centres was identical with that previously observed for heat-aggregated human IgG, but F(ab')2 fragments appeared to be retained in the germinal centres for a shorter time than aggregated IgG. Experiments with nude mice and T cell-deprived mice showed that the localization of F(ab')2 fragments does not require T cells. Competition experiments suggest that the receptor for F(ab')2 may bear little relation to the receptor for aggregated IgG. The relevance of such a lymphocyte membrane receptor to the immunopathology of rheumatoid arthritis is discussed in the light of previous findings that a proportion of the serum IgG of patients with rheumatoid arthritis has a structural anomaly compared with control IgG, characterized exposure of new determinants at the hinge region. | |
1076826 | Single-breath pulmonary diffusing capacity. Reference values and application in connective | 1976 | 1.1. Diffusing capacity of the lungs was measured by using a Mark 4 Resparameter. The single-breath diffusing capacity (D) for carbon monoxide was found to be dependent on the lung volume (VA) during the breath-hold. The same applied to D/VA and to the time constant (tau) for carbon monoxide uptake. This confirms the theoretical considerations and the results of other investigators. This effect should be taken into account especially when making serial determinations of D on the same subject. 1.2. The repeatability of the method was found to be reasonably good; the coefficient of variation was about 4% in normal subjects, as well as in a series of patients with rheumatoid arthritis. 1.3. The effect of the correction for haemoglobin concentration was calculated and tabulated for a set of possible values of DM/Vc and haemoglobin. This correction did not reduce the scatter of D values in normal subjects, but it was adopted for clinical use for theoretical reasons. Caution in its use and interpretation of the correction is emphasized. 2.1. Healthy males and females, 20-69 years of age, were examined to establish reference values for the D measurement. Multiple linear regression equations were calculated stepwise, and equations based on age and height were then used in the clinical prediction equations. Similarly, prediction equations were calculated for clinical spirometry. 2.2. The prediction equations were compared with some published reference values. The equations provide a basis for the evaluation of the effect of various factors, such as age and smoking, in different populations. 3.1. Respiratory function, clinical symptoms and chest x-ray findings were examined in patients with connective tissue diseases. Three different investigations were thus formed: a) consecutive patients (free of lung disease other than that possibly due to a connective tissue disease) with definite rheumatoid arthritis (RA, 21 cases), systemic lupus erythematosus (SLE, 18 cases) or scleroderma (SCL, 6 cases) were subjected to detailed tests. b) 129 patients from the Rheumatism Foundation Hospital, Heinola, Finland, were subjected to measurement of diffusing capacity and vital capacity in addition to chest radiography and routine clinical assessment c) the histological findings on 12 patients subjected to a needle biopsy of the lung in order to exclude other conditions were compared with the results of diffusing capacity and x-ray examinations. 3.2. Restrictive impairment of the respiratory function was the general finding in all of these groups. The reduction in diffusing capacity was out of proportion to the reduction in lung volume, however, in most cases with abnormally low values. Low D values were encountered in about half of the RA and SLE and in all of the SCL patients in group a, and in 13% of the "average" RA patients studied in Heinola. The typical histological finding in patients with reduced D was a thickening of the alveolar wall... | |
6223751 | Studies of rheumatoid synovial fluid lymphocytes. II. A comparison of their behavior with | 1983 Apr | Synovial fluid lymphocytes (SFL) and peripheral blood lymphocytes (PBL) from patients with rheumatoid arthritis were compared for their response to lectin stimulation and for their behavior in the autologous mixed lymphocyte reaction (AMLR). The SFL proliferative response to phytohemagglutinin (PHA), as measured by tritiated thymidine incorporation at 72 hr, was lower than that of PBL (P less than 0.001). When T-cell growth factor (TCGF) was added to the medium, there was an increase in the SFL proliferative response to PHA (P less than 0.05). In contrast, TCGF did not alter significantly the PBL proliferative response to PHA. Mixing experiments were performed to determine whether the poor SFL proliferative response was due to passive absorption and removal of in situ-generated TCGF by "suppressor" cells. When cultured together, SFL did not suppress the PBL proliferative response to PHA, suggesting that decreased production of TCGF rather than competitive binding of TCGF results in the poor SFL proliferative response to lectin stimulation. In the AMLR, synovial fluid non-T cells were found to be more stimulatory to peripheral blood T cells than were peripheral blood non-T cells (P less than 0.001). In comparison to peripheral blood T cells, synovial fluid T cells were poor responders in the AMLR. Repetitive in vitro autologous stimulation of peripheral blood T cells resulted in proliferative responsiveness analogous to that of SFL, i.e., a relatively poor proliferative response in the AMLR and a poor response to PHA. The latter could be augmented by TCGF. The SFL requirement for exogenous TCGF is consistent with a state of immune activation. In vivo stimulation by non-T cells may play an important role in the immune activation which characterizes rheumatoid SFL. | |
6352095 | Antigen presenting cells in situ: their identification and involvement in immunopathology. | 1983 Sep | Macrophages and other dendritic non-lymphoid cells have been shown to be functionally capable of presenting antigen to induce lymphocyte responses. These cells can now be studied in situ and distinguished, one from another, within normal tissues and sites of cellular infiltration. Analysis of the microenvironment within which these cells are found can be made with immunohistological methods using monoclonal antibodies (McAbs) and cytochemical techniques. In some cases McAbs are specific for particular types of antigen presenting cell. Using such reagents, evidence is accumulating that these cells may be intimately involved in the pathogenesis of immunoregulatory disorders. What is now required is a more definitive correlation between functional capacity and cell phenotype established with cells isolated from blood, and from normal and pathological tissues. If this is possible the immunopathologist may be able, not only to analyse complex microenvironments but also directly determine the interactions and mechanisms at play within the diseased tissues. | |
306905 | Evaluation of the simultaneous estimation of anti-dsDNA and anti-ssDNA antibodies for clin | 1978 Mar | The double-antibody solid-phase assay for DNA antibodies permits simultaneous and quantitative determination of antibodies to dsDNA and ssDNA. Using this method, 170 sera, mainly ANA-positive, were examined for the presence of anti-dsDNA and anti-ssDNA to assess the role of these antibodies in the ANA reaction. It was found that in the SLE group of patients, their ability to respond to dsDNA was correlated with the multiorgan symptomatology of disease. Anti-ssDNA titres are also highest in this group. However, anti-ssDNA titres predominate over anti-dsDNA in other collagen diseases. This predominance increases as we progress from the SLE group to undefined mild collagenosis, because the response to dsDNA decreases more than the response to ssDNA. This observation suggests that the clinical manifestation of the collagen diseases and multiorgan manifestation of SLE is linked with the pattern of response to DNA in the majority of cases. In conclusion, it appears that the determination of both ssDNA and dsDNA antibodies can be of value for the prognosis and management of patients with connective tissue disease. | |
3109 | Acid, neutral, and alkaline hydrolases in arthritic synovium. | 1976 Feb | The levels of six lysosomal enzymes (acid phosphatase, beta-acetylglucosaminidase, cathepsin D, beta-galactosidase, arylsulfatase A, and beta-glucuronidase) and four neutral and alkaline hydrolases (esterase, inorganic phyrophosphatase, alkaline phosphatase, and 5'-nucleotidase) were measured in osteoarthritic, rheumatoid and control synovia. All enzyme levels in diseased synovium except esterase values in osteoarthritis were significantly elevated compared with controls. The mean values of the group of acid hydrolases and the group of neutral and alkaline hydrolases in osteoarthritic synovia were 1.9- and 2.0-fold greater than those of control specimens. In rheumatoid synovia, the values were 4.2- and 4.5 fold greater than control for the same enzymes. Levels in rheumatoid synovia were significantly higher than those in osteoarthritic synovia with the exception of 5'-nucleotidase. Only a limited correlation between the extents of inflammation present in the synovia and the levels of a lysosomal marker enzyme (cathepsin D) was observed. These results demonstrate that whatever the mechanism, increased levels of acid hydrolases as well as certain neutral and alkaline hydrolases are present in osteoarthritic and rheumatoid synovia, and these enzymes are probably contained in the synovial lining cells. | |
807624 | Naturally occurring low molecular weight IgM in patients with rheumatoid arthritis, system | 1975 Jul | A method for purification of low molecular weight IgM (LMW IgM) which utilized salt precipitation, gel filtration, and insoluble immunoadsorbents is described. The yield from pathologic sera containing LMW IgM in the range of 15 to 36 mg% was approximately 20%. Antisera prepared against LMW IgM, IgM, and reduced-alkylated IgM recognized common determinants. Purified LMW IgM from seropositive rheumatoid subjects did not have rheumatoid factor activity in agglutination tests but demonstrated binding to 125I-labeled aggregated IgG. LMW IgM from a patient with SLE and vasculitis had anti-nuclear factor activity and anti-native DNA activity. When complexed with reduced-alkylated aggregated IgG, LMW IgM and IgM with anti-IgG activity were essentially equivalent on a weight basis in complement fixation. The source and function of LMW in biologic processes remain unknown. | |
3927458 | Effect of antirheumatic agents on the mitogen response of arthritic rat spleen cells. | 1985 Jun | Splenic lymphoid cells from rats with adjuvant induced polyarthritis show a diminished response to the T-cell mitogens Con A and PHA. This report describes the in vitro effects of various antirheumatic agents on the mitogen induced proliferative response of normal (NSC) and arthritic (ASC) rat spleen cells. Indomethacin enhanced only the arthritic responses. Other PG synthesis inhibitors such as ibuprofen and naproxen enhanced the arthritic as well as the normal spleen cell proliferative responses. Gold sodium thiomalate augmented arthritic but not normal blastogenesis. Penicillamine significantly enhanced only the Con A response of arthritic cells at 10(7)M. Levamisole produced a significant increase in the PHA response of arthritic cells and the Con A NSC response. Chloroquine diphosphate enhanced the Con A response of normal cells at 10(-5)M and 10(-6)M; both chloroquine and tilorone suppressed blastogenesis of arthritic spleen cells at 10(-4)M and 10(-5)M. When classifying antirheumatic agents as stimulator or suppressors of immune function, one must account for their effects on arthritic as well as normal lymphoid cells at the predicted pharmacologic plasma levels. | |
7038831 | [Immunofluorescence of the synovial membrane. Study of 100 cases]. | 1981 Dec | A study of the use of immunofluorescence of synovial membranes in one hundred cases of various arthropathies reveals the value of the cytoplasmic localization of immune deposits and their type (Ig) in orienting the diagnosis, the influence of therapy, the lack of correlation with optical anatomopathology of synovial tissue (performed on another tissue fragment). Certain recurrent images such as fluorescence of blood vessel walls or the presence of fibrin are of little interest; other such as the cytoplasmic fluorescence of infiltrating cells and particularly, IgG-IgM mixed cellular fluorescence or coupled fluorescence-cellular with Ig and interstitial granular with Ig and C3 orientate the diagnosis to RA. Immunofluorescence appears to be of interest for inflammatory monoarthritis and probable RA. It is less interesting when the etiological context is limited. In addition, a negative immunofluorescent study does not rule out any diagnosis. | |
7002064 | The antiperinuclear factor: II. A light microscopical and immunofluorescence study on the | 1980 Aug | The antigenic substrate of the antiperinuclear factor (APF) in human buccal mucosa cells was studied by light microscopy, cytochemistry, and the immunofluorescence technique (IFT). The cytoplasmic granules against which the APF is directed stained basophilic in light-microscopical staining techniques. The granules did not show a positive reaction product by techniques in which special chemical components are stained, and no activity of lysosomal enzymes could be identified. The use of autoantibodies and other antisera directed to distinct tissues, components, or macromolecules did not resolve the character of the antigenic granules. In addition it was shown that human vaginal epithelial cells and cryostat sections of human and rabbit buccal and oesophageal mucosa incubated with APF-positive sera showed the same fluorescent granules in the IFT as human buccal mucosa cells. Cryostat sections of rabbit buccal and oesophageal mucosa were tested as an alternative substrate in the APF test. Since the specificity as well as the sensitivity decreased when these sections were used as a substrate, they are not suitable for diagnostic purposes. | |
6965646 | The prevalence of duodenal lesions in patients with rheumatic diseases on chronic aspirin | 1980 Feb | Peroral endoscopy was performed in 56 patients with rheumatic disease who had been taking 8 or more aspirin tablets daily for more than 3 months yet who had no major gastrointestinal symptoms or history of peptic ulcer disease. Duodenal mucosal lesions were observed in 16 patients; 15 (27%) had erythema, 7 (13%) had erosions, and 2 (4%) had ulcers. The prevalence of duodenal lesions was the same in patients taking regular, buffered, or enteric-coated aspirin preparations. Patients with duodenal lesions were more likely to have associated gastric lesions. | |
6281026 | Human monoclonal autoimmune antibody produced in vitro: rheumatoid factor generated by Eps | 1982 Feb | The infection of selected lymphocytes from a rheumatoid arthritis patient with Epstein-Barr virus resulted in an immortalized cell line that secretes a monoclonal rheumatoid factor (RF). The cloned line has been growing for more than 24 months, and constantly produces a monoclonal IgM, lambda, 19S, RF (1-2 micrograms/ml/106 cells). The RF agglutinates human and rabbit IgG (but not IgM) and also protein A-coated erythrocytes, but fails to do so to mouse, goat and swine IgG-coated erythrocytes. When bound to immune complexes, this monoclonal RF dose not bind complement. In the cell supernatant RF is the only immunoglobulin and it comprises approximately 5% of the total proteins. The affinity of RF to aggregated human IgG, as detected in inhibition experiments, is higher than that of Fc receptors found on human non-T lymphocytes, K562 and Daudi cell lines. |