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

ID PMID Title PublicationDate abstract
2526687 Regulation of autoimmunity in normal and rheumatoid individuals by bone marrow-derived nat 1989 Aug Natural suppressor activity is defined as the ability of unstimulated effector cells to suppress responses of lymphoid cells to antigenic and mitogenic stimuli in an MHC unrestricted manner. We have described natural suppressor cells in bone marrow exerting such a function through a suppressor factor termed BDSF. In this report we demonstrate the ability of BDSF to regulate the in vitro EBV- and PWM-induced production of both IgM and IgM rheumatoid factor antibodies of lymphoid cells obtained from normal individuals and those with rheumatoid arthritis. BDSF therefore may play a role in the normal BM microenvironment suppressing primary IgM antibody responses. Since autoantibody responses are similarly suppressed, functional alteration or lack of BDSF may be responsible for the emergence of autoantibody-producing cells in bone marrow during certain autoimmune states.
2083945 Heterozygosity effects in studies of genetic markers and disease. 1990 Examples were discussed where heterozygosity was associated with increased or decreased disease risks and where the apparent mechanism is direct functional involvement of gene products and not linkage disequilibrium. Special attention was paid to the impact of Hp (haptoglobin) heterozygosity on a number of different multifactorial disorders. When phenotype distributions in patients show large deviations from the Hardy-Weinberg equilibrium significant differences between patients and controls may be found concerning phenotype distributions but not with respect to the frequencies of alleles and phenotypic factors. The common method of studying ratios of phenotypic factors by pooling homo- and heterozygotes is in principle a conservative approach which tends to underestimate the strength of associations and to obscure heterozygosity effects. A significant deviation from the Hardy-Weinberg equilibrium in a marker system examined in a group of patients is in itself a sensitive indicator of phenotypic association with the disease in question.
3353688 Autoantibodies from rheumatoid arthritis patients recognize antigens on the synoviocyte su 1988 Mar We have found autoantibodies in the sera from rheumatoid arthritis (RA) patients which recognize two cell surface antigens of approximately 70 kDa and 28 kDa from synoviocyte extracts as detected by immunoprecipitation analysis. These polypeptides were immunoprecipitated from extracts containing mainly macrophage-like synoviocytes (type A) but not from extracts of homogeneous fibroblast-like synoviocytes (type B). These autoantigens are not selectively expressed by RA synoviocytes, since both RA and non-rheumatoid synovia were reactive for RA sera. From the panel of different RA sera tested, 64% immunoprecipitated the 70 kDa band, and 27% recognized the 28 kDa polypeptide. These differences in the specificity of the sera seemed to be related to the clinical state of the donor. The sera from patients suffering from other autoimmune diseases such as autoimmune thyroiditis and systemic lupus erythematosus (SLE) do not appear to be reactive for these specificities, but sera from patients with Sjögren's syndrome, psoriatic arthritis, and Crohn's disease showed a weak cross-reactivity with the 70 kDa polypeptide. This autoreactivity against synovial cells in RA supports the idea that these cells participate in the initial immune response of the disease.
1925272 Rheumatoid arthritis: new findings on the failure to isolate or detect mycoplasmas by mult 1991 Jul Using 12 different and elaborate broth, agar, and cell culture procedures, we failed to isolate mycoplasmas, ureaplasmas, spiroplasmas, or chlamydiae from the synovial fluid of 10 patients with rheumatoid arthritis (RA) and from six patients with non-rheumatoid arthritis (NRA). In addition, sera from 35 patients with RA and 12 patients with NRA also were examined. Although some of the sera had moderately high titers of metabolism-inhibiting antibody to some of the 10 human Mycoplasma species, especially to the common respiratory pathogen Mycoplasma pneumoniae, and to some of the eight Ureaplasma urealyticum serovars, especially serovars V and VII, there were no significant differences between titers of these antibodies in the two groups of patients. Among RA patients serum antibody titers to M. pneumoniae were 1:32 in five and 1:16 in eight; two patients had higher synovial fluid titers (1:16) than serum titers (1:4). The geometric mean titer (GMT) of antibody to serovar V in synovial fluid was higher in RA patients than in NRA patients, but the difference did not reach significance (P = .056). Reports on the possible role of infectious agents in the pathogenesis of rheumatoid arthritis are reviewed.
2433842 [Diagnostic value of antinuclear antibodies with special reference to the immunofluorescen 1986 Nov 1 This article reviews the different immunofluorescence pattern of antinuclear antibodies (ANA) in various autoimmune diseases. Particular attention has been payed to the speckled immunofluorescence pattern, which is often caused by extractable nuclear antibodies (ENA). Clinical relevance, diagnostic significance and prognostic value are discussed in detail.
2591125 Nd:YAG laser modulation of synovial tissue metabolism. 1989 Sep In studies designed to establish the safety and efficacy of laser treatment of arthritis, the in vitro effect of Nd:YAG laser radiation on normal, osteoarthritic and rheumatoid synovial tissue and synovial fibroblast metabolism has been addressed. Defined energy levels of normal pulsed radiation (TEMoo mode) consistently up-regulated synovial tissue explant culture hyaluronic acid and protein synthesis. In contrast, high intensity Q-switched delivery down-regulated the response. The application of normal pulsed radiation had a variable effect on synovial fibroblast synthesis but the response of any given cell isolate was consistent. DNA synthesis and cell viability were not affected.
2735159 [Excessive nonspecific acral bone resorption of the margin of the distal phalangeal tubero 1989 Mar The margin of the ungual tufts corresponds to an enthesis at which, besides the dominant formation of bone, a minimal reduction of bone is also possible. This bone resorption at individual digits may concern the distral part of this margin in an augmented degree and remains stationary after a certain extent. It is not connected to any definite disease.
3552194 Bullous pemphigoid: associated diseases. 1987 Jan Bullous pemphigoid is a fairly common chronic disease of elderly persons, many of whom have other medical conditions and problems. In the main, a search for commonly associated diseases is not warranted.
3695647 Effects of reducing physical therapy services on outcomes in total joint arthroplasty. 1987 Apr A natural experiment provided an opportunity to determine whether physical therapy (PT) service reduction would affect the outcomes of total joint arthroplasty. A sample of 200 patients with rheumatoid arthritis or osteoarthritis who underwent total hip or total knee replacement during successive reduction of services was randomly selected. The demographic and clinical characteristics of patients in each period were similar. Despite large differences between groups in hours of PT per patient, there were no major differences in length of stay between the groups, or compared to similar hospitals, functional status at discharge, or numbers of surgical complications. Implications for health services organization are discussed.
2060210 Ankle arthrodesis using internal screw fixation. 1991 Jul Ankle arthrodesis treated by external fixation frequently results in complications from pin tract infections, loss of position, nonunion, and malunion. A method of ankle arthrodesis using 6.5-mm cancellous screws as the primary fixation hardware was developed. The most important screw is placed from the posterior malleolus into the neck and head of the talus, and medial and lateral malleolar screws are added to secure fixation. Near-normal anatomy is maintained with this technique because little or no bone, only cartilage, is removed. Earlier cases were all done through an anterior approach. Later, special techniques were developed for placing screws and strain-relieving bone grafting was added to promote union. Twenty-three cases that were treated by the earlier technique are reviewed. The overall fusion rate was 74%. Three conditions (avascular talus, pyarthrosis, and spasticity) were identified that placed patients at high risk for failure of fusion. Of the patients who were not in a high-risk group, only one had a delayed union. When the high-risk patients were not included in the statistics, the fusion rate was 93%. The evolved technique shows great promise for accurate and trouble-free ankle arthrodesis.
2687403 Natural killer cells and autoimmunity. 1989 In various autoimmune diseases it appears that NK activity is impaired, and that this phenomenon is significant in disease development. Impairment of NK activity may be the result of two different mechanisms. In systemic autoimmune diseases, in which various target organs are involved (nonorgan-specific), the peripheral blood NK level is generally lower than normal. This most likely allows the expression of autoimmune phenomena such as B cell hyperactivity and polyclonal antibody production, as is seen in SLE, due to a defect in the termination of the immune response. In autoimmune diseases with more localized, organ-specific lesions one can detect increased NK activity at the target organ itself. In these instances, the cytotoxic characteristic of the NK cell is more prominent. This theory explains why both increased and decreased NK activity may be observed in autoimmune diseases. In some disorders in which decreased NK activity was suspected of being crucial, immunomodulators, known to increase NK activity, were administered. Yet it is still difficult to separate the NK activity from the effect of the remaining immune system.
2595349 Computerized assessment of radiological changes of the hand in rheumatic diseases. 1989 Evaluations of radiological changes in rheumatic diseases are subject to great inconsistency. In this study, digital image analysis is shown to be a promising tool in the evaluation of joint space narrowing. The repeatability of the measurements is shown to be better than that of manual methods and is also less dependent on the observer.
3266740 HLA antigens in palindromic rheumatism. An Italian study. 1988 Dec Forty-four patients with typical palindromic rheumatism were typed for HLA-A,B,C and DR antigens. The mean duration of follow-up of our patients was 4.0 yrs. (range 1-12 yrs.). During this time 27% of patients showed a seropositivity; 22% of patients developed polyarthritis, 1 patient revealed a Sjögren syndrome and 3 patients showed a spontaneous improvement. The HLA-B16 antigen was increased in patients compared with controls, but the difference was not statistically significant. A, C and other B antigens were found with normal frequencies. The HLA-DR antigens did not reveal any differences between patients' and controls' values, either 40% of patients who developed RA carried the HLA DR4 antigen.
3618711 Hydroxychloroquine therapy in massive total doses without retinal toxicity. 1987 Aug 15 To assess the relationship between hydroxychloroquine retinal toxicity and total dose, we selectively reviewed the histories of patients who had received an additive dose exceeding 1,000 g. No retinopathy was found in nine patients treated with massive total hydroxychloroquine doses ranging from 1,054 to 3,923 g. Eight of these patients were taking recommended daily doses of 400 mg/day or less and showed no evidence of toxicity. The remaining patient treated with 600 mg/day showed evidence of preretinopathy in one eye.
2434471 Purification of a soluble phospholipase A2 from synovial fluid in rheumatoid arthritis. 1986 Nov A soluble phospholipase A2 (PLA2) was purified 4,500-fold from human rheumatoid synovial fluid. Preparative sodium dodecyl sulfate polyacrylamide gel electrophoresis yielded two bands of PLA2 activity of molecular weights 15,000 and 17,000 and pl 4.2-5.0. Purified PLA2 had absolute 2-acyl specificity, and hydrolyzed phosphatidylcholine with optimal activity at pH 7.5-8.0 and phosphatidylethanolamine with optimal activity at pH 7.0. Human synovial fluid PLA2 did not cross-react with anti-human pancreatic PLA2, as tested by radioimmunoassay.
3266994 Synovial fluid concentrations of interleukin-1 beta and proteoglycans are inversely relate 1988 Aug Interleukin-1 beta (IL-1 beta) and proteoglycans have been quantified by radioimmunoassay (IL-1 beta) and enzyme linked immunosorbent assay (proteoglycans) in synovial fluids and sera from patients with rheumatoid arthritis (RA) and reactive arthritis. All fluids were also tested for their ability to influence proteoglycan metabolism in a cartilage explant culture system. Synovial fluid IL-1 beta concentrations were inversely related to proteoglycan concentrations in samples from both RA and reactive arthritis patients (P less than 0.002 for all patients). There was no statistically significant relation between immunoreactive IL-1 beta concentration and proteoglycan synthesis or degradation in explants cultured in synovial fluid containing medium. Synovial fluid IL-1 beta concentrations were not related to erythrocyte sedimentation rate or joint total leukocyte count. IL-1 beta was not detectable (limit 250 pg/ml) in any unextracted sera. Although it appears likely that IL-1 beta is involved in the inflammatory and degenerative processes in joint disease, our findings indicate that there is no simple positive relationship between immunoreactive levels of this cytokine in synovial fluid and liberation of proteoglycans from articular cartilage as reflected in synovial fluid proteoglycan concentration.
1959267 Survivorship of cementless total knee arthroplasty without tibial plateau screw fixation. 1991 Dec Seventy-two cementless tricompartmental total knee arthroplasties were performed in 47 patients using a porous-coated prosthesis without screw fixation for the tibial components between 1984 and 1986. These individuals were observed at regular intervals for a minimum of three years. Their Hospital for Special Surgery pain and function scores as well as roentgenographic signs of anatomic alignment and subsidence were evaluated at six months, one year, and three years postoperatively. The roentgenographic evaluation for subsidence looked at a measurable difference in the anteroposterior roentgenograph on the medial and lateral plateaus and on the lateral roentgenograph anteriorly and posteriorly. Early postoperative interpretations have suggested pain and knee scores to be much lower than scores in the cemented prosthesis. Reassessment after three years, however, revealed no further deterioration of the noncemented prosthesis in respect to knee scores and survival analysis. Roentgenographic analysis showed no correlation between subsidence and alignment alterations, subsidence and time, or subsidence and pain. It appears that after an initial period of discomfort, the noncemented knee can achieve a functional, clinical, and roentgenographic result much better than previously anticipated. The consequences beyond this time period still remain unknown.
3033238 Effects of recombinant human interferons on rheumatoid arthritis B lymphocytes activated b 1987 Feb We evaluated the effects of all 3 classes of recombinant human interferon (IFN) on Epstein-Barr virus (EBV) infection of purified B lymphocytes from patients with rheumatoid arthritis (RA). After EBV infection, RA B cells secreted more IgM and significantly more IgM rheumatoid factor (RF) than normals. Spontaneous (no EBV) proliferation, IgM, and IgM RF were also higher in RA. All 3 types of IFN inhibited dose dependently EBV induced B cell activation. In RA, however, higher doses of each class of IFN were necessary to obtain 50% inhibition. IFN gamma was most potent in normals and RA. Four IgM RF production IFN gamma was significantly more potent than IFN alpha and IFN beta in reducing the spontaneous activation of RA B cells, and a similar trend was seen in B cell proliferation. These findings are discussed in the context of ongoing clinical trials with IFN gamma in RA.
2398274 Demonstration of neutralizing autoantibodies against IL-1 alpha in sera from patients with 1990 Oct 1 We have recently reported the presence of IgG which has a potent inhibitory activity against IL-1 alpha in some sera from patients with rheumatoid arthritis. The mechanism of this inhibition by IgG against IL-1 alpha is now elucidated. IgG with IL-1 alpha-inhibitory activity inhibited the binding of 125I-IL-1 alpha to receptors on rheumatoid synovial cells. In addition, preincubation of synovial cells with the inhibitory IgG did not block the binding of 125I-IL-1 alpha to receptors, suggesting a direct interaction between IgG and IL-1 alpha. To examine which region of the IgG, namely Fab or Fc region, has the inhibitory activity, the IgG was digested with papain, and Fab and Fc fragments were purified. Fab fragments, but not Fc fragments, inhibited both IL-1 alpha-induced thymocyte-proliferation and the binding of 125I-IL-1 alpha to receptors. We further demonstrated that the inhibitory IgG which was bound to protein A Sepharose could bind a significant amount of 125I-IL-1 alpha, whereas only a negligible binding of the radiolabeled ligand was detected when IgG without the inhibitory activity was used as control. Moreover, the binding of 125I-IL-1 alpha to IgG with the inhibitory activity was clearly blocked by Fab fragments of IgG having the inhibitory activity. Finally, affinity-purified IgG over an IL-alpha affinity column showed approximately 100-fold more potent inhibitory activity on IL-1 alpha-induced thymocyte proliferation compared with untreated IgG. From these results, we conclude that IgG molecules with IL-1-alpha-inhibitory activity are neutralizing autoantibodies against IL-1 alpha.
2451483 A monoclonal antibody raised by immunising mice with group A streptococci binds to agalact 1988 Mar It was shown recently that the IgG of patients with rheumatoid arthritis tends to lack the terminal galactose normally present on the conserved N-linked oligosaccharide situated on the CH2 domain. This results in the exposure of a terminal N-acetylglucosamine linked beta 1-2 to mannose. It is reported here that mice immunised with the peptidoglycan/polysaccharide complex of group A streptococci can be used as a source of monoclonal antibodies binding to this epitope. It may be significant that the organism responsible for rheumatic fever evokes antibodies binding to an abnormality of IgG found in rheumatoid arthritis.