Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 3489001 | Distribution of an anti-DNA idiotype among autoantibodies in patients with systemic lupus | 1986 Jul | Autoantibodies from patients with systemic lupus erythematosus, rheumatoid arthritis, or other connective tissue disorders were probed for the presence of a cross-reactive idiotype (AM Id) originally defined on human anti-double-stranded DNA antibodies. The AM Id was distributed primarily among antibodies to double-stranded DNA, single-stranded DNA, or cardiolipin in patients with systemic lupus erythematosus and antibodies to single-stranded DNA or cardiolipin and rheumatoid factor in patients with rheumatoid arthritis, thus tending to codistribute with the predominant primary autoantibodies in both diseases. Strong associations were observed particularly between the AM Id and anti-single-stranded DNA antibodies in patients with systemic lupus erythematosus and the AM Id and anticardiolipin antibodies in patients with rheumatoid arthritis. Affinity absorption experiments with sera from individual lupus patients showed that up to 41% of the anti-single-stranded DNA antibodies were Id positive. The results indicate that the AM Id may be widely distributed among antibodies that have a potential for binding DNA. | |
| 3131870 | Immunoregulatory mediators in the pathogenesis of rheumatoid arthritis. | 1987 | There is strong evidence for the participation of T cells, B cells and monocytes-macrophages in the local constitution of RA lesions. Such cells may create synovial damage either directly or indirectly through the secretion of mediators able to amplify immune responses and damage neighboring cells. Interleukin 1 (IL 1) can be found in RA lesions together with inhibitors of its action. Tumor necrosis factor (TNF) is another monokine able alone and in conjunction with IL 1 to stimulate bone resorption and inhibit proteoglycan synthesis. Interferon (IFN) is able to enhance the synthesis of both IL 1 and TNF in monocytes-macrophages and, in the case of IFN gamma, to induce the expression of HLA class II antigens in synovial cells. Interleukin 2 produced by activated T lymphocytes is able to induce lymphocyte proliferation and IFN gamma production. Prostaglandins produced by activated monocytes can block IL 2 and IFN gamma secretion. The exact role of this complex network of immunoregulatory mediators in the pathogenesis of RA deserves to be better elucidated. | |
| 3082226 | Willingness to pay and accept risks to cure chronic disease. | 1986 Apr | Measurements of disease burden focus most often on economic outputs--neglecting effects on quality of life. More comprehensive quantification is based on what people would pay or risk to avoid illness. Many, however, find it difficult to respond thoughtfully to hypothetical questions about what they would pay or risk. With response rates frequently under 50 per cent, the practicality of these methods has been of concern. In this study, specially trained interviewers asked 247 subjects with rheumatoid arthritis how much of their income they would pay and how large a mortal risk they would accept to achieve a hypothetical cure. Ninety-eight per cent of the subjects estimated their maximum acceptable risk (MAR) at an average 27 per cent chance of immediate death. Eighty-four per cent gave plausible responses to the willingness-to-pay (WTP) questions, with a mean WTP of 22 per cent of household income. The aspect of disease most strongly associated with WTP was impairment in activities of daily living; measured pain was most associated with MAR. The response rates achieved indicate the overall feasibility of these methods; the associations of WTP and MAR with other variables suggest systematic consideration of personal circumstances. | |
| 1659507 | The B cell repertoire in rheumatoid arthritis. II. Analysis of rheumatoid factors bearing | 1991 Sep | With the view of studying whether rheumatoid factors (RFs) produced in rheumatoid arthritis (RA) were different from those synthesized in physiological situations, we analyzed the usage of a cross-reactive idiotype (IdRQ) previously reported to be specific for RA RFs. Using EBV immortalization of circulating B cells, we prepared monoclonal RFs from patients with RA and matched controls. In both groups between 1/2 and 2/3 of the monoclonal RFs bore IdRQ. Using limiting dilution analysis, we studied the frequencies of the EBV-activated B cells able to synthesize immunoglobulins bearing IdRQ. In patients and in controls, on average, 1/3 of the RF-secreting cells used IdRQ and around 2/3 of the synthesized IgM bearing IdRQ were devoid of RF activity. These results show that precursor cells containing the germline gene encoding IdRQ are present in similar quantities in RA patients and healthy individuals, and that the IdRQ cross-reactive idiotype, although interesting for the study of the B cell repertoire, is probably not useful as a marker for susceptibility to RA. | |
| 3314204 | [Immunology of the primary inflamed joint]. | 1987 Aug 1 | The primary inflammatory rheumatic joint has a high capacity to start a local autoimmune reaction. Prototype of this reaction is the rheumatoid joint. In this review evidence is provided that the rheumatoid joint exhibits--with a high degree of certainty--autoimmune reactions of both cellular and humoral autoimmunity against IgG, Collagen of various types, proteoglycans, nuclear antigens and C3b. It is also shown that such reactions are not restricted to rheumatoid joints and may be demonstrated in other joint diseases. The local chronic immune reaction may lead to cartilage destruction through four effector cells, that is macrophages, specialised fibroblasts, chondrocytes and neutrophils. | |
| 3194726 | Physical disease and disability among 416 suicide cases in Sweden. | 1988 | All suicides occurring among the inhabitants of the County of Uppsala in Sweden between 1977 and 1984 were analyzed on the basis of information from autopsy reports and from somatic and psychiatric medical records. Among the 416 persons who committed suicide, 70 (17%) had a somatic disease of probable importance for the suicidal act. No somatic diagnosis appeared to stand out as being especially associated with a very high risk of suicide. Some diagnoses (e.g. malignant neoplasm, Parkinson's disease, multiple sclerosis) were, however, associated with a suicidal rate above that in the general population. Further knowledge about the relation between suicide and specific somatic diagnoses would be of value, since a high suicide rate in association with a particular illness might indicate insufficient medical care and rehabilitation. | |
| 3082991 | Low molecular weight IgM. Detection using immunoblotting. | 1986 Apr 3 | Two techniques for the definitive identification of low molecular weight (LMW) IgM have been compared, namely, filtration chromatography combined with nephelometry and a modified immunoblotting assay. The results indicate that the latter is a more sensitive and reliable technique. Furthermore the resolution of immunoblotting is such that it can distinguish additional oligomeric forms of IgM as well as monomeric IgM suggesting a disorder of polymerization of pentameric IgM. As the presence of LMW IgM in the sera of patients with various disorders is of prognostic significance the immunoblot technique merits consideration as a useful screening assay to detect this moiety. | |
| 2257450 | Intestinal flora of patients with rheumatoid arthritis: induction of chronic arthritis in | 1990 Dec | The composition of the obligate anaerobic intestinal flora of patients with rheumatoid arthritis (RA) differed from that of healthy subjects (HS). Total numbers of aerobes as well as anaerobic coccoid rods were found elevated when compared with HS. Eubacterium species were found in all stool samples of both groups; Bifidobacterium species were present in seven (RA) and eight (HS) out of 10 subjects. From the flora of two RA patients and two HS Eubacterium species were isolated and identified. Cell wall fragments from four E. aerofaciens strains (two from RA, two from HS) were tested for arthritis induction in rats. All four strains induced chronic arthritis which was histologically confirmed. We concluded that in the normal intestinal flora of RA patients Eubacterium species are present in high numbers (i.e. greater than 10(9)/g faeces); cell walls from isolated E. aerofaciens strains had arthropathic properties. | |
| 3787091 | Serum ferritin and free erythrocyte protoporphyrin in rheumatoid arthritis. | 1986 | In this prospective study 20 newly diagnosed patients with definite or classical rheumatoid arthritis were followed with serial measurements of serum ferritin and erythrocyte-free protoporphyrin at the beginning of the trial and at 3 and 6 months. The values were correlated with clinical disease activity ad with various laboratory parameters. It was shown that free erythrocyte protoporphyrin has a constant negative correlation with erythrocyte haemoglobin concentration independent of disease activity, while serum ferritin behaves like an acute phase protein. Initial serum ferritin or free erythrocyte protoporphyrin values or their early changes appeared to have no prognostic value as evaluated by the development of new erosions or by the response of the patient to the therapy. | |
| 2108246 | Clinical value of an integrated ELISA system for the detection of 6 autoantibodies (ssDNA, | 1990 Feb | An ELISA panel assay (ANA/6) which simultaneously detects IgG autoantibodies against 6 antigens (ssDNA, dsDNA, Sm, RNP/Sm, SSA, and SSB) was evaluated with sera from 98 patients with systemic lupus erythematosus (SLE) and related conditions, 68 disease controls, who were positive or negative by fluorescent ANA (FANA), and 100 healthy controls. The antigen panel specifically identified the particular autoantibodies present and had a high level of sensitivity which was reflected by the frequency of detection of autoantibodies in different patient groups. All active patients with SLE were positive for at least one autoantibody and 80% of these patients had 3 or more autoantibodies compared to only 20% of inactive patients. A large heterogeneity in antibody profiles was also noted. About 90% of patients with positive FANA, but no detectable autoimmune rheumatic disorder, i.e., false positive, were negative by the panel. A new method of standardization was designed to use the ANA/6 quantitatively. Very large differences in the level of all 6 autoantibodies were observed between sera from patients with active and inactive SLE, suggesting a potential usefulness of ANA/6 for patient management. | |
| 2664169 | Pharmacokinetic interactions of penicillamine in rheumatoid arthritis. | 1989 Apr | The pharmacokinetic effect of the combined treatment of penicillamine with indomethacin and chloroquine was investigated in patients with rheumatoid arthritis. The mean plasma penicillamine concentration increased by 26% during indomethacin and 34% during chloroquine treatment. This new pharmacokinetic interaction may have important clinical implications. | |
| 2941196 | Elevated antigalactosyl antibody titers reflect renal injury after gold or D-penicillamine | 1986 Aug | Titers of circulating antigalactosyl antibodies (a-Gal Ab) were assessed by passive hemagglutination using rabbit red blood cells in 40 normal subjects, in 14 patients with immunodeficient states, in 47 patients with active rheumatoid arthritis (RA), and in 15 patients with an Henoch-Schönlein disease (HS). Titers of controls ranged from 1:16 to 1:64. All immunodeficient patients exhibited very low titers (1:1). On the contrary, the existence of an enhanced humoral immune response status, as observed in RA, was not reflected by a parallel increase of a-Gal Ab titers. However, in this disease, a strong relationship existed between titers exceeding control values (greater than 1:64) and the prior occurrence of renal injury under gold or D-penicillamine therapy. Lastly, the discovery of elevated titers (greater than 1:64) in HS only when renal involvement occurred further suggests that such antibodies reflect a renal injury. | |
| 3813676 | IgM rheumatoid factor (RF), IgA RF, IgE RF, and IgG RF detected by ELISA in rheumatoid art | 1987 Jan | One hundred patients with rheumatoid arthritis (RA), of whom 73 were seropositive by latex or Waaler-Rose (WR) assays, or both, 100 healthy subjects, and 102 diseased controls (22 patients with systemic lupus erythematosus (SLE) and 80 with bronchial asthma) were evaluated for the presence of IgM rheumatoid factor (RF), IgA RF, IgE RF, and IgG RF by an enzyme linked immunosorbent assay (ELISA). Ninety two per cent, 65%, 68%, and 66% of the patients with RA were found to be positive for IgM, IgA, IgE, and IgG respectively. A positive correlation existed between the levels of IgM RF and IgA RF on the one hand and disease activity on the other, and the levels of IgM RF and IgA RF correlated with the levels of circulating immune complexes as measured by a C1q binding assay. The presence of extra-articular features also correlated positively with the levels of IgA RF and IgE RF. Five out of six patients with Sjögren's syndrome had very high levels of IgA RF. Of 47 patients typed for HLA-DR, DR1 and DR2 were significantly more frequent in those with the highest levels of IgM RF. Conversely, DR3 was associated with low levels or absence of IgA RF and IgE RF. These results suggest that immune response genes may regulate the level of different RF isotypes. The frequencies of IgM, IgA, IgE, and IgG RF were 59%, 36%, 9%, and 27% respectively in SLE and 25%, 2.5%, 70%, and 59% in bronchial asthma. | |
| 2144372 | [The rapid cytofluorometric indices of lymphocyte functional activity in rheumatoid arthri | 1990 | As many as 49 patients with rheumatoid arthritis (RA), 16 with systemic lupus erythematosus (SLE) and 40 healthy persons were examined for functional parameters of freshly isolated peripheral lymphocytes with the aid of quantitative cytofluorimetry designed by the authors. Proliferative function was estimated according to the RNA/DNA ratio in nuclear chromatin, suppressor function to the early processes of mitogenin-induced activation of B cells in the presence of prednisolone, and immunoglobulin-synthesizing function was assessed by the mean level of Ig in B cells of the population. It has been established that lymphocytes from the healthy persons are primarily in a state of rest (G0), have low B activation and high suppressor function (SF). In RA, lymphocytes, mainly B cells, are in a state of spontaneous activation (G1--S--G2) related to the degree of SF decrease. In 1/3 of patients, moderately decreased SF (to 70% of normal) controls the early processes of mitogen-dependent B activation, whereas in 2/3 of patients, a more pronounced decrease of SF (to 40% of normal) combines with hyperactivation of B cells. SLE is characterized by higher, as compared with RA, proliferative and Ig-synthesizing activity of B cells combined with a decrease of SF (to 45% of normal). High correlations have been shown: a direct one between nuclear chromatin activation and Ig-synthesis in the B cell and a reverse one between these processes and SF. The conclusion has been made that the immune status in patients with RA and SLE is marked by hyperactivation of B cells and SF decrease. | |
| 1700840 | Substance P-, calcitonin gene-related peptide- and C-flanking peptide of neuropeptide Y-im | 1990 | By means of antisera to cytoplasmic components of nerve fibres and neuropeptides which are known to be present in sensory or sympathetic nerves we have examined the distribution of both total and different types of nerve fibres in normal and inflamed human synovial tissue. Samples of synovia were obtained at surgery from five normal and five rheumatoid patients (age range 10-77 years). In order to map the overall neural innervation of the synovium, antiserum to the general neuronal marker protein gene product 9.5 was employed. Substance P and calcitonin gene-related peptide antisera were employed to identify sensory fibres and antisera to the C-flanking peptide of neuropeptide Y to distinguish sympathetic nerves. In normal synovium protein gene product 9.5-immunoreactive fibres were numerous, in particular, the vasculature was densely innervated. Free protein gene product 9.5-immunoreactive fibres were less numerous but were present in all synovia examined, and in many cases these extended to the intimal layer. Neuropeptide immunostaining was predominantly found in perivascular networks. Fibres immunoreactive for the C-flanking peptide of neuropeptide Y were exclusively located around blood vessels whereas free fibres were immunoreactive for substance P or calcitonin gene-related peptide. As with free protein gene product 9.5-immunoreactive fibres, fibres expressing substance P or calcitonin gene-related peptide immunoreactivity were often seen in the intimal cell layer. In rheumatoid arthritis a similar innervation to that seen in normal synovium was apparent in the deep tissue but fibres immunoreactive for protein gene product 9.5, the C-flanking peptide of neuropeptide Y, substance P or calcitonin gene-related peptide were not visible in the more superficial tissues or the intimal cell layer. In addition, immunostaining of neuropeptides in the deep tissue was weaker in the diseased tissues than in normal controls. The data unequivocally demonstrate that synovial tissues are richly innervated and confirm the presence of both sensory and sympathetic nerves. The absence of nerves which innervate the superficial synovium in rheumatoid arthritis might suggest that there is increased release of substance P, calcitonin gene-related peptide and the C-flanking peptide of neuropeptide Y, reducing the stores in the nerves to levels below that detectable by immunocytochemistry. However, since protein gene product 9.5-immunoreactive nerves were not seen in the inflamed tissue it is probable that synovial growth outflanks neural growth and consequently as the disease progresses neural structures become restricted to deeper tissues.(ABSTRACT TRUNCATED AT 400 WORDS) | |
| 2157088 | Platelet-derived growth factor--a growth factor with an expanding role in health and disea | 1990 Jan 19 | Platelet-derived growth factor (PDGF) is the principal mitogen for connective tissue-derived cells such as fibroblasts, smooth muscle cells, and glial cells. It is synthesized by a variety of cell types and the synthesis of PDGF and its receptors is tightly controlled. Accumulating evidence obtained in vitro and in vivo suggests that PDGF plays important roles in the pathogenesis of clinically important diseases such as atherogenesis and cancer. Moreover, PDGF is an important research tool to study the signal transmission pathway of growth factors and other hormones. | |
| 2765003 | Altered metabolism of poly(ADP-ribose) in the peripheral blood lymphocytes of patients wit | 1989 Aug | A method was developed to measure poly(ADP-ribose) metabolism in peripheral blood lymphocytes. The technique involved the isolation of lymphocytes on Ficoll gradients, followed by lysis with 5M NaCl. The synthesis and degradation of poly(ADP-ribose) in this crude lysate, measured by the incorporation of 3H-labeled NAD into acid-precipitable counts, was compared in 18 patients with systemic lupus erythematosus (SLE), 10 patients with rheumatoid arthritis, and in 10 control patients without rheumatoid arthritis. Patients with SLE showed a 70% decrease in poly(ADP-ribose) synthesis (P less than 0.001); this decreased synthesis persisted even with the addition of histones or DNase. We present possible explanations of the role of poly(ADP-ribose) in SLE. | |
| 2912457 | Treatment of chronic knee synovitis with arthroscopic synovectomy after failure of intraar | 1989 Jan | Although satisfactory results have been obtained with conventional synovectomy of the knee, there are frequent complications, and a long period of rehabilitation is necessary after this surgery. We performed arthroscopic synovectomy of the knees of 30 patients (33 knees), 22 of whom had rheumatoid arthritis. These patients underwent the procedure after failure to respond to an intraarticular injection of either osmic acid or yttrium 90. The operated knee was moved 3-5 hours after the arthroscopy, and the patients walked the next day. No rehabilitation was needed. The followup period ranged from 6 months to 36 months, with an average of 17.7 months. Except for 1 patient with severe arthritis, all patients experienced improvement. Results were rated as "good" or "very good" in 27 knees. Six months after synovectomy, the patients were asked to rate their improvement; the mean +/- SEM degree of improvement was 79.1 +/- 22.9%. All patients had significant improvement in the range of motion of the knee. One patient required manipulation of the knee (while under anesthesia) soon after the arthroscopy. There were no other complications. There was no detectable radiographic evidence of disease progression in 24 patients who were seen 1 year after the procedure or in 9 patients who were seen 2 years after the arthroscopy. Thus, arthroscopic synovectomy appears to be an effective and simple treatment for chronic knee synovitis, and has a low morbidity rate. | |
| 1365472 | A clinical comparison of two leading non-steroidal anti-inflammatory drugs. | 1991 | One hundred patients with rheumatoid arthritis were entered into a randomised, double-blind, cross-over study of naproxen (500 mg b.d.) and diclofenac (50 mg t.i.d.). Each treatment period lasted four weeks with a wash-out period of up to one week on admission and again between periods of active therapy. Compared with baseline, both treatments significantly reduced the duration of morning stiffness, Ritchie Articular Index, daytime and night-time pain and produced a significant improvement in the disease status. Forty-two non-serious presumed side-effects were reported in 21 patients (21%). All were characterised by common everyday signs and symptoms. These largely related to the upper gastrointestinal tract and typical of those commonly reported for non-steroidal anti-inflammatory agents. There were no statistically significant differences between the two treatments for any of the efficacy parameters or in the incidence of side-effects. Patients also expressed an equal preference for the two drugs. | |
| 2046396 | Total knee arthroplasty: a population-based study. | 1991 Jun | Total knee arthroplasty (TKA) is being used increasingly for the management of chronic arthritis of the knee. In this report, we review the frequency of application of TKA in the population of Olmsted County, Minnesota, from 1971 through 1986. The utilization rate of TKA increased from 20.5 per 100,000 person-years for 1971 through 1974 to 60.8 per 100,000 for 1983 through 1986. Although rates were higher in women, they increased with advancing age in both sexes. Rates between the urban and rural populations of Olmsted County did not differ. The two most common underlying diseases that necessitated TKA were osteoarthritis and rheumatoid arthritis; they were the cause of more than 90% of all operations. By extrapolating the rates of TKA in Olmsted County to the total 1986 US population, we estimate a need for at least 143,000 TKAs annually at a direct cost of more than $2.3 billion each year. |