Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 2942556 | Serum from patients with autoimmune diseases induces in vitro production of disease-associ | 1986 Sep | Antibodies present in serum of patients with rheumatoid arthritis (RA), autoimmune thyroid diseases, and myasthenia gravis are preferentially cytotoxic to suppressor T lymphocytes from normal subjects induced by Concanavalin A. The aim of this study was to determine whether the lymphocytotoxic antibodies found in patients with these diseases also react with regulatory T cells to facilitate production of the autoantibodies responsible for each disease. Peripheral blood mononuclear cells (PBMC) from normal subjects were treated with serum from patients and complement. After washing, residual viable cells were cultured with pokeweed mitogen for 7 days. Immunoglobulin M rheumatoid factor and antihuman thyroglobulin antibody (anti-hTgAb) in the culture supernatants were measured by RIA. Anti-hTgAb was produced in culture supernatants of PBMC treated with serum samples from patients with autoimmune thyroid diseases, whereas serum samples from patients with RA, myasthemia gravis, or normal subjects did not stimulate production of detectable anti-hTgAb. In contrast, Immunoglobulin M rheumatoid factor was produced by normal PBMC treated only with serum from patients with RA. When normal T cells treated with serum were cultured with autologous untreated non-T cells in the presence of pokeweed mitogen, autoantibodies also were produced. Furthermore, the production of anti-hTgAb was suppressed by adding untreated T cells to the mixture of treated T cells and untreated non-T cells. These results suggest that lymphocytotoxic antibodies found in patients with autoimmune disorders may cause disease-associated suppressor T cell dysfunction. | |
| 2716007 | Pregnancy outcome and autoantibodies in connective tissue disease. | 1989 Jan | Pregnancy outcome before and after onset of disease and the association with present levels of anticardiolipin antibodies (aCL) and other autoantibodies were investigated in rheumatoid arthritis (RA) (117 patients), systemic lupus erythematosus (SLE) (74 patients), and systemic sclerosis (28 patients). Although 78% of the 81 pregnancies in patients with systemic sclerosis occurred before disease onset, pregnancy loss rate was highest in this disease (44%) but in RA (17%) and SLE (18%) was similar to a control population (16%). Elevated levels of IgG aCL were present in one of 4 patients with RA, in one of 5 patients with systemic sclerosis and in the only patient with SLE to have recurrent previous pregnancy loss. Congenital heart block occurred in one of 28 pregnancies from 17 anti-Ro (SSA) positive women with SLE. | |
| 3097789 | Cryoglobulins and pyroglobulins: an overview. | 1986 Apr | Cryoglobulins are serum proteins with heterogeneous etiopathogenetic and immunochemical properties. What they have in common is temperature-dependent insolubility, in that at temperatures below 37 degrees C (often around 4 degrees C) they precipitate, and then redissolve at 37 degrees C. When the etiopathogenesis of the cryoglobulinemia is unknown, which is true for many patients, the condition is called idiopathic or essential cryoglobulinemia, whereas it is termed secondary whenever it appears to be associated with one of several diseases. Cryoglobulinemia has indeed been found in patients with lymphoproliferative and autoimmune disorders, liver diseases, infectious (viral, bacterial, fungal and parasitic) diseases, and so on. Cryoglobulins are usually classified according to their immunochemical properties as single-type monoclonal, mixtures of a monoclonal Ig with non-immunoglobulin material (DNA, lipoprotein, complement), mixed with one monoclonal Ig or mixed polyclonal, in which constitutive Ig fractions are polyclonal. As compared with normal Ig, cryoimmunoglobulins have sometimes been found to exhibit a peculiar amino acid structure of their heavy chains, less often of their light chains as well, and to have a lower carbohydrate content. Such structural abnormalities may contribute to their loss of solubility at low temperatures, possibly associated to the steric changes induced by the low temperature, causing the precipitate to form. The most common clinical features of cryoglobulins are correlated with vasculitis in the various organs and sometimes with increased viscosity of the plasma. Signs and symptoms include purpura, ulcers of the extremities, arthralgia, proteinuria, hepatic damage, abdominal pain, congestive heart failure, mental confusion, oligo-anuria, hemorrhagic diathesis, and coma. Pyroglobulins are also serum proteins with temperature-dependent insolubility. However, although they precipitate out of serum heated at 56 degrees C for half an hour, they do not resolubilize when the serum is returned to 37 degrees C. Pyroglobulins have been mainly found in patients with lymphoproliferative diseases (especially Waldenström's macroglobulinemia, with or without cryoglobulinemia), systemic lupus erythematosus, and neoplasia. So far, only single monoclonal IgG, IgM or IgA pyroglobulins have been described. Since they precipitate only at 56 degrees C, pyroglobulins do not cause clinical symptoms and they are usually discovered by chance. | |
| 2097845 | [The level of IgM, IgG and IgA antibodies and total antibodies to the low-molecular, cell- | 1990 Nov | The levels of IgM, IgG and IgA antibodies, as well as total antibodies, to group A streptococcal low-molecular cell-wall protein without type specificity were studied in the sera of patients with primary erysipelas, rheumatism in the active and inactive phases, seronegative rheumatoid arthritis, as well as in the sera of healthy donors. The average level of antibodies to low-molecular protein in the sera of all groups of patients was significantly higher than the sera of healthy donors. The analysis of the distribution of antibodies in accordance with their isotypes revealed the specific features of response, characteristic of each group of patients. For rheumatism patients, the positive correlation between response to low-molecular protein and response to group-specific polysaccharide A was established. This correlation was most pronounced in patients with rheumatism in the inactive phase. | |
| 3129275 | Plasminogen activators and tiaprofenic acid in inflammation. A preliminary study. | 1988 | Treatment with tiaprofenic acid appreciably reduced the level of plasminogen activators in the medium of 3T3-Balb mouse fibroblasts, as revealed by both a fibrin plate assay and amidolytic determination with chromogenic substrates. At the same time, tiaprofenic acid was able to inhibit the production of plasminogen activators induced by phorbol myristate acetate, a powerful inflammation and tumour promoter, added to the cell monolayers. By isolating the inhibitors of plasminogen activators it was possible to show that the decrease of fibrinolytic activity produced by tiaprofenic acid is not related to an increase of inhibitors. Rather, a decrease of activators seems to take place. Synovial fluid samples from 4 patients before and after treatment with tiaprofenic acid were also assayed for plasminogen activator activity by the fibrin lysis method. In 3 of the 4 cases a marked decrease after treatment was evident. The one unresponsive patient suffered from a para-neoplastic arthritis. | |
| 2512638 | Depressed plasma fibrinolytic activity in a group of patients with connective tissue disea | 1989 | In various connective tissue disorders, a depressed fibrinolytic activity of the blood, attributed a contributory role in the development of disease, has been reported. We have determined selected fibrinolysis variables of the blood in 16 patients (7 patients with mixed connective tissue disease, 4 with systemic lupus erythematosus, 3 with rheumatoid arthritis and 2 with systemic sclerosis) and in 16 apparently healthy, age- and sex-matched controls. A significantly reduced mean activity of the intrinsic derived, urokinase-like plasminogen activator was found in the patient group. None of the other variables, including the extrinsic plasminogen activator (t-PA), differed from the control group. Possible implications of our findings in relation to the patho-physiology of these connective tissue diseases are discussed. | |
| 2419908 | Human protein HC and its IgA complex are inhibitors of neutrophil chemotaxis. | 1986 Mar | Protein HC, a heterogeneously charged low molecular weight glycoprotein, and its IgA complex were isolated from human plasma and urine. Plasma from individuals with monoclonal IgA populations was used as starting material for the isolation of the protein HC-IgA complex to obtain homogeneous complex populations. Neither low molecular weight protein HC nor its IgA complex in the concentrations 30 and 600 mg/liter influenced the random migration of normal human neutrophils. The chemotactic response of neutrophils to endotoxin-activated serum was, however, attenuated in a dose-dependent way by both low molecular weight protein HC and protein HC-IgA complex. Concentrations of protein HC and its IgA complex producing significant inhibition of the chemotactic response were found to occur in plasma from healthy and diseased individuals as well as in synovial fluid from patients with rheumatoid arthritis. These results suggest that protein HC and its IgA complex play physiological roles in the regulation of the inflammatory response. | |
| 2204120 | Acute rheumatic fever in adults. | 1990 Sep 15 | Thirty-one adults with acute rheumatic fever were identified at Groote Schuur Hospital over a 10-year period. In keeping with other series, arthritis was the most common major criterion. However, unlike other series, cardiac involvement was a prominent feature. Two patients died and a further 4 required valve replacements as a result of the disease. This suggests that local factors are of importance in determining the morbidity of the disease and that physicians should consider acute rheumatic disease in adults who present with unexplained valvular disease or carditis. | |
| 2821153 | DNA receptor dysfunction in systemic lupus erythematosus and kindred disorders. Induction | 1987 Oct 1 | The ability of sera from patients with SLE and similar connective tissue diseases to induce dysfunction of the receptor for DNA was studied. All SLE and MCTD sera studied resulted in marked inhibition of DNA receptor binding. Furthermore, the sera from a subgroup of patients with other rheumatic diseases and a surprisingly high percentage of asymptomatic relatives of SLE patients exhibited a similar effect. The humoral factors causing this defect were shown to be of at least three reactivities: (a) antibodies to DNA, (b) antibodies to histones, and (c) antibodies to the DNA receptor itself. The reactivity of anti-DNA and antihistone antibodies is dependent upon intact cell-surface DNA, and reconstitution experiments suggest that antihistone antibodies are reactive with histones complexed to this DNA, which in turn is bound to the DNA receptor. Cells with an antibody-induced DNA receptor defect are unable to bind DNA; the subsequent inability to degrade DNA may have important consequences in diseases such as SLE in which DNA-anti-DNA immune complexes are of pathogenetic significance. | |
| 1968795 | Identification and characterization of IgA and Vicia villosa-binding T cell subsets in rhe | 1990 Feb | Autoimmunity may be due to augmentation of immune responses by human CD8 cells which bind the lectin Vicia villosa (VV). We have investigated T cells in rheumatoid arthritis (RA) by double immunofluorescence flow cytometry, in order to assess VV-binding CD8 and CD4 cells from the peripheral blood and synovial fluid. A significant increase in CD8+VV adherent (P less than 0.0001) and CD4+VV adherent cells (P less than 0.001) was found in synovial fluid, as compared with peripheral blood from patients with RA. A significant increase in VV-binding CD8+ or CD4+ cells was, however, not found in the blood of patients with RA, as compared with controls. We suggest that the lack of VV-binding T cells separated from blood, in contrast to those from synovial fluid, may be due to an inhibiting agent expressing N-acetyl D-galactosamine. Indeed, IgA1 is rich in N-acetyl D-galactosamine, it inhibits VV binding to T cells and is significantly bound to CD8 cells (P less than 0.001). The IgA1 was then characterized and in about half the patients J chains and secretory component was found, suggesting that the IgA1 is of the polymeric and secretory variety. IgA bound to the T cells engaged the Fc alpha receptors and a significant decrease in the Fc alpha receptors was found in CD8 cells (P less than 0.0001) and CD4 cells (P less than 0.01). Desorption studies were then carried out on CD8 and CD4 cells which showed that a loss of cell-bound IgA1 was associated with an increase in VV binding. Conversely, adsorption of IgA to T cells was associated with a loss in VV binding. The results suggest that the failure of VV binding to CD8+ and CD4+ cells from peripheral blood of patients with RA can be ascribed to cell-bound IgA1. Cytophilic IgA1 may inhibit the function of CD8+VV binding cells, thereby preventing augmentation of the systemic immune response, consistent with the lack of extra-articular disease in these patients with RA. | |
| 1697756 | Genes for MHC, TCR and MIs determine susceptibility to collagen induced arthritis. | 1990 Jul | Type II collagen induced arthritis (CIA) in mice is an animal model for polyarthritis. The susceptibility to the disease is linked to the class II genes of H-2 gene complex (MHC). The susceptibility requires T cells expressing certain receptors coded by the V beta genes. Further, the MIs gene products in combination with the class II molecules can up- or down-regulate the T cells involved in the disease. The disease is mediated by the presentation of an arthritogenic epitope on the collagen type II peptide by the MHC class II molecule, which is recognized by a T cell expressing certain V beta receptors, triggering the autoimmune response. These studies point out possible mechanisms of rheumatoid arthritis in humans and suggest various methods of immune intervention to down-regulate the disease. | |
| 3091636 | Basis for defective responses of rheumatoid arthritis synovial fluid lymphocytes to anti-C | 1986 Sep | Synovial fluid mononuclear cells (SFMC) from patients with active rheumatoid arthritis characteristically respond poorly to mitogens. In this study, mitogenic antibodies reactive with the CD3(T3) antigen on human T lymphocytes were used to analyze the basis for the deficiency. OKT3-induced proliferation and release of interleukin 1 (IL-1) and interleukin 2 (IL-2) from SFMC were depressed in all patients. Purified IL-1 or recombinant IL-2 restored proliferative responses in SFMC and increased IL-2 receptor density. Exogenous IL-1 also enhanced IL-2 release. Fractionation of SFMC supernatants on phosphocellulose columns revealed the presence of IL-1 and a potent IL-1 inhibitor. The monocyte-derived IL-1 inhibitor blocked IL-1-dependent responses of normal peripheral blood lymphocytes to OKT3, but had no effect on IL-2-dependent events. These results suggest that IL-1 inhibitor(s) in SFMC impair(s) OKT3-induced mitogenesis by interfering with the effects of IL-1 on T lymphocytes. The net result is deficient IL-2 secretion, IL-2 receptor expression, and impaired cellular proliferation. This novel inhibitory circuit provides a rational explanation for the diminished function of synovial fluid T lymphocytes in rheumatoid arthritis patients. | |
| 3779322 | Comparison of methotrexate with azathioprine or 6-mercaptopurine in refractory rheumatoid | 1986 Nov | Methotrexate (MTX) appears to be useful in patients with rheumatoid arthritis (RA) refractory to other drugs but its long-term toxicity and efficacy are uncertain. A retrospective study of MTX in such patients in comparison with the purine analogues, azathioprine and 6-mercaptopurine was made using life-table analysis. Eighty-four patients took MTX in a median dose of 7.5 mg/week whilst 55 received purine analogues, 100 mg/day (median). By 12 months, 19.3% of patients had ceased MTX due to toxicity, compared with 29.3% for purine analogues. Toxicity severe enough to warrant stopping therapy was uncommon after 8 months with either drug. At 12 months 61.5% of the MTX patients had achieved defined criteria of improvement compared with 25.6% for the purine analogues (p less than 0.05). The number of patients improving on purine analogues did not increase substantially after 6 months, whereas the number improving with MTX continued to 12 months. MTX in a low-dose regimen is useful in refractory RA and superior to low-dose purine analogues. | |
| 3625637 | Sexual quality-of-life of patients with arthritis compared to arthritis-free controls. | 1987 Jun | The influence of arthritis upon sexual satisfaction and activity and patient receptivity to sexual rehabilitation was investigated by interviewing 169 patients with arthritis and 130 controls. Patients differed from controls in their greater loss of sexual satisfaction over time, but they were comparably satisfied with their current sexual adjustment. They reported similar reductions in frequency of intercourse over time. Joint symptoms and fatigue disturbed the sexual adjustment of patients more than controls, but damaged body image, worry about partner interest, loss of libido and loss of lubrication did not. There was receptivity to a program of sexual rehabilitation among patients and controls that was not dependent upon sexual dissatisfaction. | |
| 12412746 | Impaired autologous mixed lymphocyte reaction (AMLR) reactivity of peripheral blood T cell | 1989 Nov | We examined AMLR reactivity of unseparated T cells and CD4+ and CD8+ T cell subsets in peripheral blood from 11 rheumatoid arthritis (RA) patients and 10 healthy controls. T cell subsets were isolated by negative selection using complement mediated cytotoxicity. AMLR reactivity of six patients (designated RA-L was reduced below the range of the controls' responses. Five patients (designated RA-N) exhibited normal AMLR reactivity. We observed impaired AMLR reactivity of CD4+ T cells from RA-L relative to RA-N and healthy controls (P < 0.05). CD4+ T cell reactivity of RA-L was reconstituted to normal with pharmacological doses of recombinant interleukin-2 (IL-2) (100 U/ml). In contrast, CD8+ T cells from RA-L in the presence of 100 U/ml IL-2 exhibited markedly impaired AMLR reactivity relative to RA-N and healthy controls (P < 0.05). Dose-response studies revealed partial reconstitution of CD4 T cells with physiological concentrations of IL-2 (10 U/ml). To examine the possibility that in vivo pre-activation of T cells in RA accounted for the findings, T cells or subsets were cultured alone for 7 days in the presence of 100 U/ml IL-2. A trend toward enhanced reactivity of CD4+ and CD8+ T cells in L-RA relative to N-RA and healthy controls was observed, but the differences were not statistically significant. There was no correlation between reactivity of T cells alone in the presence of IL-2 and AMLR reactivity. The results suggest the possibility that abnormal AMLR reactivity of CD4+ and CD8+ T cell subsets in RA may arise as a consequence of different pathophysiological mechanisms. | |
| 3261154 | In vitro response to influenza immunisation by peripheral blood mononuclear cells from pat | 1988 Jul | Reduced in vitro anti-influenza antibody response by peripheral blood mononuclear cells (PBMs) after vaccination was confirmed in a group of 28 patients with systemic lupus erythematosus (SLE), and also in 16 patients with some other autoimmune syndromes. This group of patients with SLE had higher serum anti-DNA binding, but there was no evidence of increased autoantibody production after vaccination, nor any clinical or laboratory evidence of flares in disease activity that are sometimes seen to follow intercurrent infection. Although a reduced in vitro antibody response may, to some extent, reflect redistribution of antibody producing cells, there appears to be more generalised impairment of the immune response in these patients, which cannot be accounted for by steroid/immunosuppressive therapy. | |
| 2259842 | Methotrexate therapy in rheumatoid arthritis patients diminishes lectin-induced mononuclea | 1990 | Methotrexate (MTX) is an anti-folate drug used in cancer chemotherapy because of its anti-proliferative effects. However, it is unclear whether the anti-proliferative effects of MTX contribute to the efficacy of low-dose MTX in the treatment of rheumatoid arthritis (RA). To date, either no change or a paradoxical increase in lectin-induced proliferation has been observed in cultures of peripheral blood mononuclear cells (PBMC) from MTX-treated RA patients (RA + MTX). In these earlier studies, high folate-containing media and tritiated thymidine (3H-TdR) were used. Our studies were designed to test the hypothesis that the use of a culture medium with a low folate content along with tritiated deoxyuridine (3H-UdR) permits detection of diminished phytohemagglutinin (PHA)-induced proliferative responses of PBMC from RA + MTX. The data demonstrate decreased PHA-induced cellular proliferation of cultured PBMC from RA + MTX compared with controls. When comparing the PBMC proliferative responses in high vs low folate medium, a significantly greater increase (P less than 0.05) in proliferation occurs in the cells from RA + MTX cultured in the high folate medium. This suggests that an in vivo folate-deficient state of the cells from RA + MTX may be corrected in vitro when a high folate medium is used in culture. We conclude that the use of 3H-UdR and a medium containing folate within the normal range of plasma folate levels eliminates artifacts associated with the use of high folate medium and 3H-TdR, which obscures the anti-proliferative effect of MTX in RA patients. | |
| 2744071 | A pharmacokinetic study of the active metabolite of nabumetone in young healthy subjects a | 1989 | We have performed a detailed pharmacokinetic study of the plasma concentrations of the major active metabolite of nabumetone, 6-methoxy-2-naphthylacetic acid (6 MNA), attained after a single dose and during chronic administration comparing the results of a group of young healthy volunteers with those of a group of elderly arthritic patients. The latter had higher peak plasma concentrations of 6 MNA and slower rates of elimination but there is no tendency for the drug to accumulate unpredictably in the old. Disease activity also influences plasma concentration, those with more active disease, and lower serum albumin concentrations had lower AUC values. | |
| 1688303 | A non-cytotoxic suppressor of immunoglobulin synthesis and secretion by B cells of normal | 1991 | A factor secreted by thymocytes of immunized rabbits totally suppressed both the initiation of, and ongoing synthesis and secretion of, lectin (PWM)-induced synthesis of IgM and IgG immunoglobulins by the circulating B lymphocytes of normal humans, and of twenty consecutive patients with rheumatoid arthritis and twelve consecutive patients with systemic lupus erythematosus. The suppressor factor, referred to as human Ig synthesis/secretion suppressor factor or HISSF, is not HLA restricted in its activity and is not cytotoxic to the circulating human mononuclear cells (B cells, T cells, Null cells and monocytes). It was demonstrated that T cells precultured with HISSF were transformed into suppressor cells which, when added to fresh cultures of autologous B cells, suppressed the synthesis and secretion of IgM and IgG. On the basis of its suppressive and non-cytotoxic properties in vitro, HISSF may be an effective immunosuppressant in the treatment of patients with autoimmune diseases. | |
| 3789817 | Immune complexes in synovial fluid and serum from patients with disseminated gonococcal in | 1986 Oct | Twenty one patients with acute arthritis associated with disseminated gonococcal infection (DGI) were studied. Synovial fluid (SF) from 14 and serum from 15 (matched in eight) were assayed for the presence of immune complexes (IC) by the Raji cell immunofluorescent assay (Raji IFA) and the 125I-Clq polyethylene glycol (PEG) binding assay. Higher levels and frequency of IC were detected in the SF by both IC assays and these were associated with a significant increase in complexes containing IgM over serum (p less than 0.02). Complexes containing IgG were found predominantly in serum and were infrequent in SF (p less than 0.003). These data suggest that the arthritis of DGI may result from primary immune complex formation within the synovial cavity after local antibody synthesis within the synovium in response to gonococcal seeding. |