Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 3802575 | High prevalence of anti-mitochondrial antibodies among patients with some well-defined con | 1986 Oct | A sensitive enzyme linked immunosorbent assay for determination of low levels of anti-mitochondrial antibodies (AMA) has been developed. With this method, sera from patients with primary biliary cirrhosis (PBC) and patients with different connective tissue diseases were investigated. Ninety percent of PBC sera were found to harbour high levels of AMA and a high proportion of patients with systemic lupus erythematosus (SLE), but also other patients with connective tissue diseases were found to have low affinity or low concentrations of AMA in their sera. AMA positive sera were further investigated with sodium dodecyl sulphate polyacrylamide gel electrophoresis and immunoblotting technique. PBC showed reactivity to 70, 50 and 45 kD mitochondrial polypeptides. SLE sera showed reactivity to 70 and 45 kD polypeptides and furthermore to a 65 kD polypeptide. Many of the AMA positive sera from patients with connective tissue diseases reacted to a 65 kD polypeptide. | |
| 2481879 | Pathways of mononuclear cell infiltration in rheumatoid synovitis. | 1989 | The mononuclear cell infiltration which characterizes the chronic inflammatory reaction results from the migration of lymphocytes and monocytes through the endothelium of the postcapillary venule. The initial step in the emigration of these cells in their binding to the vascular endothelium. The binding capacity of the endothelial cell (EC) for lymphocytes and monocytes is increased by IFN-gamma, IL-1, TNF alpha, and TNF beta. Production of these cytokines by chronic inflammatory cells may be expected to amplify the chronic inflammatory reaction. Initiation of the chronic synovitis of rheumatoid and other chronic synovitides probably results from the interaction of antigen with sensitized T cells in the sublining region of the synovium. This interaction is facilitated by the presence of substantial numbers of DR + macrophage + accessory cells in the synovial interstitial space. It is likely that these accessory cells are bone marrow derived monocytes migrating to the synovial lining layer in response to chemotactic factors released by the hyperplastic synovial lining cells. Lymphocytes differ in their binding affinity for ECs, and more strongly binding lymphocytes may be preferentially bound. Since binding is the first step in lymphocyte emigration, this event may lead to the selection of more strongly binding lymphocytes in the perivascular infiltrate. The T cells present in the mononuclear cell infiltrates of rheumatoid arthritis, other chronic synovitides, and multiple sclerosis have been shown to be composed largely of the CDw29 + CD4+, helper-inducer, memory cell subset. The predominance of this T-cell subset may result from its demonstrated greater binding affinity for ECs.(ABSTRACT TRUNCATED AT 250 WORDS) | |
| 2530345 | Selective loss of the CD4+ inducers of suppressor T cell subsets (2H4+) in active systemic | 1989 Oct | We investigated 2H4+ and 4B4+ T cell subsets from the purified CD4+ helper/inducer and CD8+ suppressor/cytotoxic T cells in circulating blood of 15 patients with severe active systemic lupus erythematosus (SLE), 6 patients with inactive SLE, 5 patients with rheumatoid arthritis and seven healthy controls. The percentage of the total CD4+ T cells increased and CD8+ T cells decreased in all patients with active SLE. Of interest, however, all the patients with active SLE and central nervous system (CNS) disease had a selective decrease in the percentage of CD4+ 2H4+ T cell subsets in circulating blood that is responsible for induction of the CD8+ suppressor T cells. This loss of the CD4+ 2H4+ T cells was accompanied by an increase in the CD4+ 4B4+ T cell subsets, that are the true helper/inducers providing help for B cell immunoglobulin production. A marked decrease in the CD4+ 2H4+ cell subsets in the circulating blood of all patients with severe active SLE and CNS disease is related with meaningful functional properties of the T cells in an abnormal immune system. | |
| 1702808 | Molecular analysis of IgM rheumatoid factor binding to chimeric IgG. | 1991 Jan 15 | To localize regions on IgG bound by rheumatoid factors (RF), we studied IgM RF binding to chimeric IgG antibodies consisting of murine V regions fused to human constant regions. Using a modified RF ELISA, we showed that polyclonal RF from rheumatoid arthritis patients bound IgG1, 2, and 4 strongly; IgG3 was also bound, although less well. The majority of 18 monoclonal RF from patients with Waldenstrom's macroglobulinemia bound IgG1, 2, and 4 only. In contrast to RF from RA, 14 of 18 monoclonal RF did not react with IgG3. Only 3 of 18 monoclonal RF bound IgG3 well. By shuffling C region domains between IgG3 and IgG4, we showed that sequence variation in the CH3 domain is responsible for the differential binding of monoclonal RF to IgG3 and IgG4. Hybrid IgG3/IgG4 antibodies containing the CH3 domain of IgG4 were bound by monoclonal RF, whereas those containing the CH3 domain of IgG3 were not. To evaluate the contribution of the N-linked carbohydrate moiety at Asn-297 to RF binding sites on IgG, we measured RF binding to aglycosylated IgG antibodies produced by mutating Asn-297 to another amino acid. Glycosylated and aglycosylated IgG1, 2, and 4 were bound identically by monoclonal and polyclonal RF. Aglycosylated IgG3, however, was bound better than glycosylated IgG3 by polyclonal RF and by IgG3-reactive monoclonal RF. | |
| 3127586 | Antithymocyte globulin in the treatment of gold induced severe aplastic anemia. | 1988 Jan | Severe aplastic anemia is the most serious complication of chrysotherapy. No treatment for this condition has been demonstrated effective. We report 3 patients with gold induced severe aplastic anemia treated with antithymocyte globulin. Complete marrow recovery was obtained in 1 case and a partial but satisfactory response in the other. All the patients remain alive without requiring blood transfusion after followup of longer than 16 months. | |
| 3095247 | Studies on Hanganutziu-Deicher antigens-antibodies. I. Hanganutziu-Deicher antibodies of I | 1986 | Sera of patients with various liver diseases were examined for the presence of Hanganutziu-Deicher (H-D) antibodies by enzyme immunoassay with high-molecular weight glycoprotein (HMWGP) isolated from bovine red blood cell stromata. IgG class H-D antibodies were demonstrated in sera of 5.9% of acute hepatitis, 28.1% of chronic hepatitis and 21.9% of liver cirrhosis patients. H-D specificity of the antibodies under investigation was determined by absorption experiments. Evidence was also presented that the H-D antibodies in the liver disease sera are directed to N-glycolyl neuraminic acid (NGNA) and/or NGNA-dependent determinants of HMWGP. | |
| 2190313 | [Cyclosporin in autoimmune diseases]. | 1990 May 26 | The efficacy of cyclosporine (Sandimmun) is well established in the field of organ transplantation. More recently, prospective controlled trials were performed in patients with other diseases. The efficacy of cyclosporine for the following clinical entities was proven by the trials: endogenous uveitis, rheumatoid arthritis, Sjögren's syndrome, myasthenia gravis, psoriasis and Crohn's disease. Furthermore, there is evidence from a controlled trial of some benefit for patients with aplastic anemia. The proteinuria of patients with glomerulonephritis was reduced by cyclosporine, though no improvement in glomerular filtration rate was observed. Large controlled trials in patients with multiple sclerosis or amyotrophic lateral sclerosis revealed a beneficial effect on some clinical parameters. Nevertheless, cyclosporine cannot be recommended for these patients at the present time, since the ratio between the (slight) beneficial effects and the side effects was unfavourable. In patients with primary biliary cirrhosis, cholestasis slightly diminished after the administration of cyclosporine. Whether this improvement in laboratory parameters predicts an improved outcome in patients with primary biliary cirrhosis has yet to be demonstrated. Some patients with recently diagnosed insulin dependent diabetes needed no further insulin therapy as long as cyclosporine was administered. This is an observation of tremendous potential practical relevance for the future, when methodology may be available for diagnosing autoimmune destruction of beta-cells before clinically overt diabetes is present. Cyclosporine combined with prednisone was slightly more efficacious in patients with Graves' ophthalmopathy than prednisone alone. For all other autoimmune diseases, no controlled studies with cyclosporine are available at the present time. The most important side effects of cyclosporine are renal dysfunction, hypertension, gout, tremor, gingival hyperplasia and hypertrichosis. These side effects are manageable by appropriate dosage of cyclosporine and prophylactic measures. Side effects caused interruption of cyclosporine therapy in less than 5% of the patients. Thus, cyclosporine appears to be an efficacious new agent for treatment of some groups of patient with immune diseases. | |
| 2893438 | T cell regulatory disturbances in the rheumatic diseases. | 1987 Dec | Significant immunoregulatory abnormalities have been described in both SLE and RA. In SLE, deficient suppressor T cell activity may result from depletion of CD8+ suppressor precursors, depletion of CD4+ suppressor-inducer cells, or impaired lymphokine production and deficient CD4+ cell activation of suppression by CD4+ cells. The net result is an apparent failure to inhibit antibody synthesis. The defects in RA are less well defined, although in RA there also is evidence that either deficient suppression or deficient suppression-induction plays a role in the pathogenesis of disease. There is evidence for local lymphocyte activation in the synovium, with possibly impaired local immunoregulation. However, the precise nature of the immune reactions in the synovium and their relationship to systemic immunoregulatory abnormalities remain unclear. | |
| 3099800 | HLA-DR antigens in gold-induced neutropenia. | 1986 Dec | We studied the clinical courses of 9 patients who developed acute gold-induced neutropenia with marrow aplasia. Eight of these carried HLA-DR4, compared with only 2 of 9 who had mild, chronic, isolated neutropenia (P less than 0.05). Only 1 of 9 patients with myelotoxicity carried HLA-DR3. We conclude that these groups are immunogenetically distinct, and that HLA-DR3 is not a significant risk factor for severe gold-induced neutropenia. | |
| 2888943 | Blood and protein loss via small-intestinal inflammation induced by non-steroidal anti-inf | 1987 Sep 26 | Nearly three-quarters of patients on long-term treatment with non-steroidal anti-inflammatory drugs (NSAIDs) have small-intestinal inflammation, the consequences of which are largely unknown. Two potentially important complications, blood and protein loss from the small intestine, have been studied. 49 patients on NSAIDs underwent study with an indium-111 labelled leucocyte technique which localises and measures intestinal inflammation. 32 patients underwent simultaneous study with technetium-99m labelled red blood cells (RBC), which showed identical sites of localisation to 111In-leucocytes in 19. Intestinal blood loss was measured in 8 patients by use of chromium-51 labelled RBC, and a significant correlation between blood loss and intestinal inflammation was found. Intestinal protein loss was assessed in 9 patients with 51Cr-labelled proteins; patients with NSAID-induced small-intestinal inflammation were found to have a protein-losing enteropathy. These studies show that small intestinal inflammation caused by NSAIDs is associated with blood and protein loss, both of which may contribute to the general ill-health of rheumatic patients. | |
| 1836278 | Immune responses to 18.6 and 30-kDa mycobacterial antigens in rheumatoid patients, and V b | 1991 Dec | We have investigated both the humoral and the cellular immune responses of patients with juvenile rheumatoid arthritis (JRA) and rheumatoid arthritis (RA) to mycobacterial antigens. The JRA group was not Bacillus Calmette Guerin (BCG) vaccinated whilst the majority of the RA group was. As determined by immunoblotting, 79% of sera from patients with JRA reacted mainly with a 18.6-kDa protein (P18.6), whilst 70% of sera from patients with RA reacted mainly with a 30-kDa protein (P30) of BCG, M. tuberculosis and M. kansasii. In contrast, only a moderate proportion of the control sera (25% of adult and 20% of children) showed reactivity to P30, and none of the samples had significant reactivity with the P18.6 antigen. Furthermore, T-cell proliferation to the P18.6 and P30 antigens was detected in the majority of JRA and RA patients, and was nearly always higher in synovial fluid (SF) than in the peripheral blood (PB). We also investigated the usage of V beta family genes in P18.6 and P30 antigen-specific T-cell lines established from the SF of one patient with active RA. We showed that V beta 2, -4, -5, -6, -7, -14, -17, -18 and V beta 19 were over-represented compared with other known V beta families. We also noted that the proportion of V beta 14 was higher in freshly isolated SF mononuclear cells compared with the blood in this patient and in 2 out of 4 other RA patients examined. Other V beta families such as V beta 6, V beta 8, V beta 16, V beta 18 and V beta 19 were also over-represented in the SF compared with the blood in some patients. Taken together our results provide more information concerning the role of mycobacterial antigens in RA and suggest that there may be an in vivo clonal expansion of T lymphocytes in the synovium. | |
| 2608274 | [Peri-prosthesis fractures in total hip endoprostheses]. | 1989 Nov | Periprosthetic fractures after total hip arthroplasty (THA) were found in 0.77% (33 fractures in 4280 THA). At the time of fracture the prosthesis was loose in about one-third of the cases. In most cases (63%), the fracture was located at the distal end of the prosthesis. Fractures at this location were transverse or short oblique; those situated more distally were spiral. Whereas those located along the prosthesis shaft were long oblique. Open reduction internal fixation was performed immediately for all fractures. Thirty patients were followed an average of 2.7 years (1 year-11 years) after fracture. In 28 cases stabilization was obtained using a plate. In 2 cases the prosthesis was changed at the same time as plate stabilization. 1 case the lossened prosthesis was converted to a Girdlestone. A primary change in the prosthesis without osteosynthesis was performed in 2 cases. One year after operation all fractures were healed. We recommend a large DC plate for fractures distal to the tip of the prosthesis (spiral fractures). In cases of stable THA, we stabilized the fracture at the level of the tip of the prosthesis or along the shaft of the prosthesis itself, using a wave plate with corticocancellous bone graft. Fractures along the loosened prosthesis but with good bone stock are treated by implantation of a long-stem prosthesis. If bone stock is poor, we recommend the fracture be stabilized using a plate. Only after the fracture is healed do we revise the prosthesis. | |
| 3118018 | Expression of HLA-DR, DQ and DP antigens and interleukin-2 receptor on synovial fluid T ly | 1987 Aug | Synovial fluid and peripheral blood T lymphocytes were examined from 10 patients with rheumatoid arthritis and 2 controls. T lymphocytes from inflammatory fluids were activated as shown by their increased size and expression of class II MHC antigens. Of the T cells, 60% were DR positive, 19% DP positive and 29% DQ positive. More Leu 2a than Leu 3a cells were HLA-DR positive. In contrast, few T cells expressed Tac. We conclude that T cell activation is taking place but is incomplete or "frustrated". | |
| 2978115 | Defective induction of T-cell help and natural killing following anti-CD3 stimulation of a | 1988 Aug | Anti-CD3 monoclonal antibody (MoAb) stimulates T cells in normal peripheral blood to proliferate and develop cytotoxic activity against NK-sensitive tumor cell lines. We now find that anti-CD3 MoAb also generates cytotoxic activity against a cell line (MEL-21) resistant to classical NK cell killing. After activation in vitro with anti-CD3 MoAb for 18 h, normal peripheral blood mononuclear cells (PBMNC) develop more HLA-DR-positive helper than suppressor T cells, manifest a functional helper effect as measured by increased IgG synthesis (P less than 0.01), as well as kill MEL-21 target cells. PBMNC from rheumatoid arthritis (RA) patients respond normally but mononuclear cells from rheumatoid arthritis synovial fluid (RASF) respond poorly. PBMNC from systemic lupus erythematosus (SLE) patients also respond poorly to anti-CD3 stimulation. Thus, the ability of anti-CD3 to stimulate IgG production and generate enhanced natural cytolytic activity are defective in both RASF and SLE lymphocytes. | |
| 3706932 | Impotence in scleroderma. | 1986 Jun | Hormonal, neurologic, and vascular factors affecting potency were evaluated in 10 men with scleroderma and in 10 age-matched men with rheumatoid arthritis. Impotence was reported by 6 of the patients with scleroderma and none with rheumatoid arthritis. Studies of serum testosterone, free testosterone index, follicle-stimulating hormone, luteinizing hormone, prolactin, estradiol, thyroxine, and thyrotropin did not show a hormonal basis for impotence in any patient. Neurologic causes were not found on physical examination. Penile blood pressures were markedly abnormal in 4 impotent patients, intermediate in 2 impotent and 3 potent patients, and normal in 11 potent patients. A history of claudication and diminished ankle blood pressures indicated large vessel disease in 2 impotent patients; the remaining 4 impotent men had normal ankle pressures, suggesting that their poor penile blood pressures and impotence were due to small vessel disease, perhaps the small artery lesions of scleroderma. | |
| 2541464 | Carpal tunnel: MR imaging. Part II. Carpal tunnel syndrome. | 1989 Jun | The magnetic resonance (MR) images of 14 wrists of patients with carpal tunnel syndrome (CTS) were studied. Four general findings visible regardless of the cause of CTS included swelling of the median nerve, best evaluated at the level of the pisiform bone; flattening of the median nerve, most reliably judged at the hamate level; palmar bowing of the flexor retinaculum, best visualized at the level of the hamate bone; and increased signal intensity of the median nerve on T2-weighted images. Findings related to cause were tendon sheath edema in traumatic tenosynovitis, synovial hypertrophy in rheumatoid tenosynovitis, a ganglion cyst, and excessive amount of fat within the carpal tunnel, a persistent median artery, and a large adductor pollicis muscle. Knowledge of these findings may permit more rational choice of treatment. In four cases in which symptoms persisted after surgery, findings valuable in explaining or predicting the failure included incomplete incision of the flexor retinaculum, excessive fat within the carpal tunnel, persistent neuritis of the median nerve, and development of neuromas. | |
| 2971484 | Suppressor cell activity of human alveolar macrophages in interstitial lung diseases. | 1988 Jul | It has been shown that alveolar macrophages (AM) are able to modulate lymphocyte proliferation in vitro. The purpose of this study was to evaluate the effect of AM on the proliferation of autologous peripheral lymphocytes (APL) in patients with interstitial lung disease (ILD) compared to controls. Thirty patients were investigated: eight with idiopathic pulmonary fibrosis (IPF), nine with sarcoidosis(SA), seven with rheumatoid arthritis (RA) and six controls (CO). AM and APL were co-cultured at an increasing macrophage/lymphocyte ratio: 1%, 10%, 20% and 50%. A dose-dependent effect was observed and related to the number of AM added to APL, enhancing at low ratios and suppressing at high ratios. Suppression of proliferation by 50% AM differed in the four groups tested: 94.6% (92-98) in IPF, 73.0% (49-100) in SA, 43% (25-57) in RA, 32.4% (22-41) in the CO (P less than 0.01, P less than 0.05, and P0.05 respectively, compared to CO). Suppressive cell activity of AM from patients with ILD was higher than suppressive cell activity of the CO group. Suppression with 10% of AM in ILD group was 18% (2.2-62) compared with 2.58% (-13-17) in the CO group (P less than 0.05). 20% AM in ILD group showed 35% (3-76) suppression in comparison with 9.76% (-11-27) in the control group (P less than 0.01), 50% AM in ILD have a suppressive activity of 71% (25-100) in contrast to 32.4% (22-41) in control (P less than 0.01). In conclusion, AM from patients with interstitial lung diseases have a significantly stronger suppressive effect on the proliferation of autologous peripheral lymphocytes than controls. This is a new aspect of the study of activation of AM in these kinds of disorders. | |
| 2261739 | Chemoattractant production by synovial fluid cells in chronic arthritis. A study with a ne | 1990 Sep | A new method was developed to study the migration of lymphocytes under in vitro conditions. Attractant fluid was added to the appropriate lower wells, which were filled to the brim. Peripheral blood mononuclear cells were labelled with 51Cr and then put into the upper wells. Surface tension and capillary force are enough to make clamping of these plates possible, separated by a polycarbonate filter, 15 microns thick with a pore size of 8 microns, between these two standard multiwell microculture plates. After three hours of incubation at +37 degrees C in a humidified 5% CO2 atmosphere, the migrated cells were harvested from the lower wells using a semiautomatic harvester, and the radioactivity was counted. The present method makes it unnecessary to enrich or select for different cell subsets for migration studies. Instead, density gradient separated mononuclear cells as such can be used to assess their migratory capacity. | |
| 1903808 | Prevalence of mucosal lesions in the stomach and duodenum due to chronic use of NSAID in p | 1991 Mar | We review preliminary findings of the screening and prophylaxis phases of a study of misoprostol in patients with arthritis receiving nonsteroidal antiinflammatory drugs (NSAID). Endoscopic evaluation of over 1,800 patients with rheumatoid arthritis or osteoarthritis, more than 95% of whom qualified for screening on the basis of continuous NSAID use over the prior 6 months, has revealed clinically significant gastroduodenal lesions in 37% and ulceration in 24%. In the prophylaxis phase, patients without significant lesions were randomized to receive misoprostol or placebo and NSAID therapy with diclofenac for 52 weeks. Product-limit and crude incidence analyses of data from patients thus far enrolled indicate that misoprostol is associated with significant protection against the development of gastroduodenal lesions compared with placebo after 12 or 24 weeks of study. No adverse effect of misoprostol administration on underlying arthritis activity has been observed thus far. Definitive conclusions await completion of the study. | |
| 2946717 | In vitro studies on the Fc-receptor function of mononuclear phagocytes in rheumatoid arthr | 1986 Nov | The Fc-receptor (Fc-R) function of monocytes isolated from 19 control subjects and from 30 patients presenting with a rheumatoid arthritis (RA) was assessed in vitro by a classical rosette assay using IgG-coated sheep red blood cells. In RA patients, the percentage of monocytes forming rosettes was significantly lower than in controls (34.4 +/- 20.4 versus 67.4 +/- 4.5%; P less than 0.001). The blockade observed was reversed by a prior trypsin treatment of RA monocytes, the percentage of recovery being correlated with the IgG plasma levels. Besides, IgG purified from the serum of four RA patients bound a mean of 7.3, 5.2, 1.6, and 1.6 times more than normal IgG did onto concanavalin A (Con A), peanut agglutinin (PNA), phytohemagglutinin (PHA), and pokeweed mitogen (PWM), respectively. Although similar amounts of 125I-labeled normal and RA IgG were bound to normal monocytes, RA IgG inhibited more efficiently than normal IgG the Fc-R function of normal monocytes, for all concentrations tested (10 to 100 micrograms/100 microliters). A prior treatment of RA IgG by alpha-mannosidase, but not by beta-galactosidase, significantly reduced their inhibitory properties. The incubation of monocytes with D-mannose or mannan reduced their capacity to form rosettes. The percentage of monocytes forming rosettes in the presence of both mannan and normal IgG was significantly lower than that measured in the presence of normal IgG only. On the contrary, the rosetting capacity of monocytes in the presence of both RA IgG and mannan was the same as that calculated in the presence of RA IgG only. The inhibitory effect of RA IgG was not related to their abnormal circular dichroism. Our data suggest that the greater ability of RA IgG to block the Fc-R function of monocytes probably depends on the presence of a greater number of accessible mannosyl residues on the glycosidic side chains located in the Fc domain of the molecules. |