Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 3616455 | [Characterization of chronic lymphocytic proliferation in a female patient having rheumato | 1987 May | The authors have studied the case of a female patient with rheumatoid polyarthritis, who developed a lymphocytic proliferation in the blood, the marrow, and the liver, associated with a neutropenia. Several similar cases have been recently reported in the literature. The cellular proliferation is made of large granulous lymphocytes and the study of membrane markers enables to find the following homogeneous phenotype: E rosette+, CD8+, HNK-1+, FcR+, CD4-luminal diameter "divided by degrees - -, IgS-, HLA class II-. This lymphocytic sub-population produces little interleukin-2, responds weakly to mitogens (PHA, CON A, PWM), and inhibits the response of normal lymphocytes to the same mitogens. These lymphocytes have a weak natural killer activity but, on the contrary, develop a very strong cytotoxic activity which is antibody-dependent. Clinically, splenomegaly, anemia and infections are frequent and hepatomegaly or thrombopenia more rare. Adenopathies are never present. The evolution is chronic in nature and not very aggressive, although the lymphocytic proliferation is monoclonal in origin, as demonstrated in molecular biology studies. The neutropenia might be secondary to an inhibiting effect of lymphocytes on the granular precursors of the bone marrow. There is a definite association between this lympho-proliferative syndrome and rheumatoid polyarthritis, and this association appears to be different from the Felty's syndrome. | |
| 3311050 | A low molecular weight, heat-labile factor enhances neutrophil Fc receptor-mediated lysoso | 1987 Sep | When exposed to solid-phase immune complexes, polymorphonuclear neutrophils (PMN) degranulate and release proteases capable of degrading the major structural macromolecules of the joint. Evidence indicates that the PMN response to such activators may be modified by factors present at the sites of inflammation. We have evaluated the effects of a low molecular weight factor present in synovial fluid from rheumatoid arthritis (RA) patients on Fc receptor-mediated PMN degranulation and phagocytosis. Synovial fluid samples from 11 RA patients were studied; 10 of them contained factor(s) which augmented phagocytosis and degranulation mediated through the Fc receptor. This factor(s) alone, however, did not initiate neutrophil degranulation: its MW is less than 10,000 daltons and it is unstable when heated to 56 degrees C. We also examined supernatants that were produced by coculturing adherent human mononuclear cells stimulated by IgG-coated sheep red blood cells with autologous nonadherent mononuclear cells. A factor(s) with properties similar to those found in the synovial fluids (i.e., heat-labile at 56 degrees C and capable of augmenting Fc receptor-mediated degranulation and phagocytosis) was found in the stimulated human mononuclear cell culture supernatants. Filtration studies indicated that the MW of this factor(s) is between 2,000 and 10,000 daltons. No such activity was detected in culture supernatants of unstimulated mononuclear cells. Production of the cytokine was blocked by cycloheximide, indicating that protein synthesis was necessary. This factor(s), by enhancing PMN degranulation, may augment PMN-mediated tissue destruction in diseases such as RA. | |
| 2325051 | Identification of patients at risk for gastropathy associated with NSAID use. | 1990 Feb | It is suggested that gastropathy associated with nonsteroidal antiinflammatory drugs (NSAID) is the most frequent and, in aggregate, the most severe drug side effect in the United States. This work is based on a consecutive series of 2,400 patients with rheumatoid arthritis (RA) followed prospectively for an average of 3.5 years by the American Rheumatism Association Medical Information System. We present a preliminary exploration of the magnitude of the problem, the population at risk and the patients within that population who are at particularly high risk. Patients on NSAID had a hazard ratio for gastrointestinal (GI) hospitalization that was 6.45 times that of patients not on NSAID. Characteristically, patients at high risk for GI hospitalization and GI death are older, have had previous upper abdominal pain, have previously stopped NSAID due to GI side effects and have previously used antacids or histamine2-receptor antagonists for GI side effects. These patients also frequently take corticosteroids. Patients attributing relatively minor symptoms to NSAID tend to be younger and female. Our preliminary analysis is univariate; since these variables are interdependent, firm conclusions regarding the relative importance of these risk factors require development of multivariate risk factor models. The syndrome of NSAID-associated gastropathy can be estimated to account for at least 2,600 deaths and 20,000 hospitalizations each year in patients with RA alone. | |
| 3631074 | Analysis of genetic interrelationship among HLA-associated diseases. | 1987 Sep | We have developed a method to study the genetic relationship between any two HLA-associated diseases. We have considered the following hypotheses: (1) both diseases are caused by a common allele; (2) different alleles at the same locus predispose to the two diseases; (3) one disease is predisposed by two alleles, one of which can also lead to the second disease; and (4) different HLA-linked loci are involved in the etiology of each disease. For each hypothesis, we have derived the expected HLA haplotype-sharing distribution in sib pairs who are affected with two diseases. The comparison of the expectations indicate that, in many cases, the alternate hypotheses can be distinguished, if the sample size is appropriately large. The knowledge of the mode of inheritance of each disease is not usually necessary; however, it can greatly increase the power of the test. Analyses of data on pairwise combinations of rheumatoid arthritis (RA), autoimmune thyroid disease (ATD), and insulin-dependent (type I) diabetes mellitus (IDDM) suggest that (a) IDDM is predisposed by two HLA-linked alleles, one of which also predisposes to ATD, (b) one of the IDDM alleles also confers susceptibility to RA, and (c) although the HLA-linked susceptibilities to RA and ATD appear to be primarily due to distinct alleles, the ATD allele may also have a minor role in predisposition to RA. | |
| 3791699 | Decreased interleukin 2 inhibitor in sera of patients with autoimmune disorders. | 1986 Aug | The lymphokine, interleukin 2 (IL-2), is an important modulator of cell-mediated immune (CMI) responses. We report here the detection of an inhibitor of IL-2 in normal sera by measuring the inhibition of thymidine incorporation in IL-2 dependent murine CTLL cells. The inhibitor, partially purified by Sephacryl S-200 gel filtration, eluted with the 60,000-70,000 mol. wt fraction. The factor was destroyed at 56 degrees C for 30 min and did not bind to Protein A Sepharose, suggesting that it is not an immunoglobulin G. Of 26 normal sera tested, 23 had significant levels of the inhibitor. Since connective tissue diseases are often associated with deficient CMI responses, we examined the levels of IL-2 inhibitor in 26 systemic lupus erythematosus (SLE) and 22 rheumatoid arthritis (RA) patients. Only 8 SLE and 12 RA patients had normal levels of the inhibitor. Of the 18 SLE patients with low or undetectable levels, 15 had clinically defined active disease and of the eight with normal levels, three had active disease. The decrease in the IL-2 inhibitor level did not correlate either with steroid or cyclophosphamide treatment or with serum levels of DNA binding and C3. These data suggest that the function of the inhibitor is to control IL-2 activity under normal conditions. Decreased levels of the IL-2 inhibitor in these patients might be explained either as a reduced requirement of this regulatory protein secondary to decreased IL-2 production or a defect of the cells responsible for the production of both IL-2 and its inhibitor. | |
| 3399794 | Antigen-induced tenosynovitis in hypersensitized rabbits: a model for rheumatoid tenosynov | 1988 | Rabbits were first immunized and later challenged with the same antigen (bovine serum albumin, or ferritin) by injection into the tibialis anterior tendon. Inflammatory changes of the tenosynovium and epitenon included infiltration by neutrophils (early) and mononuclear cells (later) over a 6-week course of tenosynovitis. A pattern of antigen entrapment in the tendon together with immunoglobulin was shown by use of radiolabelled antigen and immunochemical staining. Half-life of antigen in the tissues averaged 5 days over the 6-week period. Changes in the epitenon included cellular necrosis, appearance of phagocytic cells, and disruption of the collagen matrix. Tissues of control animals (challenged without prior immunization) showed minimal changes and significantly less retention of antigen (P greater than 0.005). The model is relevant to the mechanism of tendon damage associated with antigen-driven chronic inflammation, as may be the case in rheumatoid arthritis. | |
| 2964079 | Immunoregulatory lymphokines in rheumatoid joints. II. Production by and responsiveness to | 1987 | Since the role of interleukin-2 (IL-2) in rheumatoid synovial joints has been debated, we examined IL-2 production by, and IL-2 responsiveness of, cells eluted from synovial tissue (ST) of patients with rheumatoid arthritis (RA) and juvenile rheumatoid arthritis (JRA). IL-2 was not detected in unstimulated cell-culture supernatants from any of the four RA patients tested, but it was present in small amounts in supernatants of unstimulated cultures derived from three of seven JRA patients studied. After PHA stimulation, IL-2 was detected in corresponding supernatants from all RA and JRA patients and from normal mononuclear cells (MNC). There was no significant difference in IL-2 activity between supernatants of normal MNC and supernatants from either RA or JRA patients. The eluted cells showed a proliferative response to recombinant IL-2. Rheumatoid ST cells are thus able to produce and respond to IL-2. Since non-T cells present in the eluates might interfere with IL-2 metabolism, one cannot yet say whether T cells of rheumatoid ST themselves produce and respond to IL-2 in a normal or abnormal way. | |
| 2225648 | Two- to four-year results of posterior cruciate-sparing condylar total knee arthroplasty w | 1990 Nov | One hundred fourteen hybrid Press-Fit Condylar total knee arthroplasties (TKAs) were reviewed an average of 2.8 years after surgery to determine if this method of implantation provided satisfactory results compared with conventional cemented TKAs. Ninety-three percent of the knees had good or excellent results, and 94% of the knees had at most only mild or occasional pain. One knee with a metal-backed patella was revised for mechanical failure of the patellar button. Roentgenographic analysis of the femoral component interface showed that 30% of knees had a radiolucent line in at least one zone. However, none of the lines was wider than 1 mm, and none was about the central stem. There were no signs of loosening about any of the components. It was concluded that hybrid TKA provides a good and predictable result that is comparable to cemented TKA. | |
| 2919080 | Effect of posterior cruciate sacrifice on durability of the cement-bone interface. A nine- | 1989 Jan | This article presents a survivorship analysis of the second conservative 100 primary total-condylar knee arthroplasties in 75 patients performed between 1979 and 1980, with a maximum follow-up of 9 years. With this type of knee arthroplasty, the posterior cruciate ligament is routinely sacrificed. Survivorship results revealed that 98.9 per cent of the knees had good outcome at 9 years of follow-up, using revision surgery for aseptic and septic loosening and radiographic evidence of global radiolucency or shift of the component as endpoint. Radiographic survivorship analysis showed well-fixed components in 87 per cent of implants, using endpoint criteria of appearance and progression of radiolucency under tibial component. Sacrificing the posterior cruciate ligament does not adversely affect durability of fixation of the total-condylar knee arthroplasty. Bone cement provides an excellent fixation of total knee implant. | |
| 3382449 | Chondrocalcinosis in surgically resected joints. | 1988 Jun | To investigate the association between chondrocalcinosis (CC) and osteoarthritis (OA), 338 joint specimens were examined histologically (55 knees and 84 hips surgically resected because of idiopathic OA, 106 control knees obtained postmortem, and 93 fractured hips). The risk for CC in the OA knees was sixfold that of the age- and sex-adjusted control sections. CC occurred much less frequently in the hip than in the knee; the association with OA was less clear-cut. It was not possible to resolve by statistical analysis which of the two pathological processes was the horse and which was the cart. | |
| 3106630 | Gold induced ulcerative proctitis: report and review of the literature. | 1987 Feb | A case of ulcerative proctitis complicating chrysotherapy for rheumatoid arthritis and a literature review of gold induced enterocolitis is presented. Only 26 patients have been reported with this complication. No specific therapy is available, except supportive measures and cessation of gold therapy. | |
| 3753841 | Clinical characteristics and prognosis of myasthenia gravis with other autoimmune diseases | 1986 Feb | Of 277 patients with myasthenia gravis (MG) who underwent thymectomy, including 78 with thymomatous MG, 33 patients had other autoimmune diseases. The clinical characteristics of MG with other autoimmune disease were investigated. Graves's disease and rheumatoid arthritis were the most common autoimmune diseases seen. The association rate of autoimmune disease in patients with thymomatous MG (3.8%) was significantly lower than that in patients with nonthymomatous MG (15.1%). The positive rate for a germinal center in the thymus was significantly higher in patients with other autoimmune disease than in those without such disease. Thymectomy was effective for MG in patients with an associated disease as well as in those without such a complication. The clinical course of the associated autoimmune disease did not seem to be adversely affected by thymectomy. Therefore, thymectomy should be performed in MG patients with other autoimmune disease. | |
| 2431580 | HLA genotypes in a family with a case of homozygous C2 deficiency and discoid lupus erythe | 1986 | A fifty-year-old man with a history of recurrent bronchial and renal infections, and rheumatoid arthritis was admitted with a sunexposure-induced discoid lupus erythematosus. Complement levels and HLA typing of the patient and his family revealed a homozygous C2 deficiency in the patient and his HLA-identical healthy younger sister. The C2 deficiency gene was associated with HLA-A10, B18, DR2, C4A4B2, BfS on one chromosome and with HLA-A2, B7, DR2, C4A4B2, BfS on the other. | |
| 2937602 | beta-Endorphin, immunological and biochemical changes in synovial fluid in rheumatic disor | 1986 Jan | In 120 patients with rheumatic disorders concomitant assays of serum and synovial fluid were done for acute phase reactants, immunoglobulins and the neuropeptide beta-endorphin. One-third of the patients with rheumatoid disease demonstrated synovial fluid levels of endorphin to be several-fold higher than serum levels, while in two-thirds the opposite results were found. These changes are discussed as adaptive or defense mechanisms. The synovial membrane is postulated to synthesize beta-endorphin. | |
| 1657009 | Gene expression (collagenase, tissue inhibitor of metalloproteinases, complement, and HLA- | 1991 Sep | In situ hybridization was used to localize and quantify gene expression in rheumatoid arthritis (RA) and osteoarthritis (OA) synovial tissue. Collagenase, tissue inhibitor of metalloproteinases (TIMP), HLA-DR, and complement (C2 and C3) gene expression was studied in synovial tissue from 23 patients with RA, OA, or other inflammatory arthropathies. Gene expression was highly compartmentalized: Collagenase, TIMP, and C2 messenger RNA (mRNA) were localized primarily to the synovial lining layer; HLA-DR mRNA was prominent in the lining and in some sublining lymphoid aggregates; the C3 probe hybridized only to sublining lymphoid aggregates. Relative mRNA levels were quantified using computer-assisted image analysis. There was significantly more collagenase, C2, C3, and HLA-DR mRNA in RA compared with OA patients. However, TIMP mRNA levels were similar in RA and OA. Expression of collagenase, TIMP, C2, C3, and HLA-DR genes correlated with the degree of synovial inflammation. The effect of intraarticular corticosteroid injection on synovial tissue gene expression was studied using serial percutaneous synovial biopsy samples from the knees of 3 RA patients. Joints were biopsied, injected with triamcinolone, and rebiopsied 1-2 weeks later. Histologic inflammation scores were lower in posttreatment synovia. Collagenase and TIMP mRNA, although abundant in presteroid samples, were nearly undetectable in post-steroid tissues. HLA-DR mRNA levels also were significantly decreased. C2 and C3 hybridization significantly decreased in 2 of 3 patients and 1 of 3 patients, respectively. Hence, clinical response to intraarticular steroid therapy was accompanied by histologic improvement and decreased expression of genes that play a role in articular destruction.(ABSTRACT TRUNCATED AT 250 WORDS) | |
| 2200263 | Multicenter study of recombinant human erythropoietin in correction of anemia in rheumatoi | 1990 Aug | PURPOSE: To administer recombinant erythropoietin to patients with rheumatoid arthritis who had significant anemia, while monitoring hematologic and rheumatologic clinical responses as well as potential toxicity. PATIENTS AND METHODS: Seventeen patients with rheumatoid arthritis from five rheumatology care settings were studied. The patients had initial hematocrits of 34% or less and stable clinical status, and were not being treated with second-line drugs or corticosteroids. An 8-week randomized double-blind study involving various dosages of recombinant erythropoietin, as well as placebo, was followed by a 24-week open-label study in which dosage could be titrated to achieve a normal hematocrit. RESULTS: In the 8-week randomized study, four of 13 patients who received injections of recombinant erythropoietin showed a hematologic response, arbitrarily defined as at least a 6-unit increase in hematocrit. None of four placebo-treated patients showed a meaningful hematologic response. All 11 patients who completed the subsequent 24-week open-label study reached a normal hematocrit level at some time during the study, and 10 of 11 showed an increase of hematocrit 6 units or greater. At least one adjustment, i.e., an increase, decrease, or omission of the erythropoietin dosage, was required in all patients to maintain the hematocrit at a target range of 35% for women or 40% for men. Meaningful changes were not seen in patients' capacity to perform activities of daily living or pain levels during either the 8-week randomized study or the 24-week open-label study. No adverse effects were associated with recombinant erythropoietin therapy. CONCLUSION: Patients with rheumatoid arthritis showed excellent hematologic responses to recombinant erythropoietin, without toxicity, during careful monitoring for appropriate dosage adjustment, although a meaningful change in rheumatologic clinical status was not seen. | |
| 2558410 | Differential immunological response of patients with rheumatoid arthritis towards two diff | 1989 | An abnormal immune response towards the Epstein-Barr virus (EBV) has been documented in patients with rheumatoid arthritis (RA). To investigate whether these findings are due to the transformation event caused by EBV, RA blood mononuclear cells and monocyte-enriched preparations were incubated with two different EBV strains: the transforming virus secreted by the cell line B95-8 and the virus released by the P3HR-1 cell line that is not able to transform due to a small deletion in the U2 region of the virus genome. Immunological response was determined by the production of interleukin-1 (IL-1) and tumor necrosis factor (TNF) using ELISA and bioassay systems. There was a striking difference in cytokine measurements with a strong inhibition of IL-1 and TNF production after incubation with the B95-8 virus, but not the P3HR-1 virus. These data indicate that the disturbed reaction of the immune system towards EBV is either dependent on the full transformation of B cells in RA patients or alternatively due to the secretion of a cytokine inhibitor by the B95-8 cell line. | |
| 2141558 | Degradation of aggregates of activated C3 (C3b) by monocytes of patients with rheumatoid a | 1990 May | We investigated whether a decreased complement receptor expression or function of monocytes isolated from peripheral blood of 52 patients with rheumatoid arthritis (RA) and rheumatoid vasculitis (RV) could account for the previously observed diminished degradation of immune complexes by monocytes of patients with RA and RV. On average, monocytes from all patients expressed significantly less CR1, and degraded significantly less AC3b when compared with monocytes of healthy controls. In addition, monocytes from RV patients degraded significantly less AC3b when compared with monocytes from patients with RA. The expression of both CR1 and CR3 on monocytes of RV patients was lower compared with RA patients but this difference was only significant for CR3. No differences were found between AC3b degradation and the expression of CR1 and CR3 between patients with active and inactive RA. Using linear discriminant analysis on the variables AC3b, CR1 and CR3, 94% of the patients could be classified correctly as healthy controls, RA or RV, suggesting a true multi-variate relationship between these parameters and patients groups. Our results suggest that the diminished capacity of monocytes from RA patients to degrade AC3b is due partly to a decreased expression of CR1 and CR3. | |
| 1982000 | Human neutrophil elastase: degradation of basement membrane components and immunolocalizat | 1990 Nov | Human neutrophil elastase was purified to homogeneity as two isozymes named E1 and E2. The isozymes degraded Type IV collagen, laminin, fibronectin, and heparan sulfate proteoglycan similarly to each other. The degradation of such basement membrane components by elastase may assist the extravasation of neutrophils in the process of inflammation. Among the substrates tested, only type V collagen, which is susceptible to neutrophil gelatinase, was resistant to elastase. This broad substrate specificity of the enzyme may also contribute to tissue destruction at the sites of inflammation. We produced a monoclonal antibody against the purified enzyme and applied it to immunohistochemical studies. In bronchopneumonia and polyarteritis nodosa, elastase was associated with the cleaved elastic fibers, indicating that the enzyme really destroys tissue in vivo. In the exudates of rheumatoid joint, elastase was stained as diffuse fine granules. Immunohistochemical studies with the monoclonal antibody will provide a complementary way to disclose the mechanism of diseases related to neutrophil infiltration. | |
| 3577315 | [Recent aspects of antirheumatic therapy in the elderly]. | 1987 Jan | Consequences have to be derived in respect to the antirheumatic treatment from recent withdrawals of several non-steroidal anti-inflammatory drugs (NSAID). This especially applies for elderly patients with reduced renal function. The dosage has to be carefully adjusted to the individual problems of the patient. No attempts should be made to achieve a completely pain-free state by use of highest dosages: the lower the dose maintaining the patient's mobility, the safer the therapy. NSAID with long elimination half-life time carry a special risk of adverse effects for the elderly due to accumulation. Reduced renal function of the elderly may also result in hypertension and heart failure. Combination of NSAID with glucocorticoids may enhance the antiinflammatory effect, but also causes an increase of adverse effects. Therefore, the combined use appears to be justified only in special situations of severe inflammatory activity no sufficiently controlled by NSAID in which the glucocorticoids are used in the lowest effective dose applied according to the circadian rhythm. The duration of treatment is to be limited, since the adverse effects of glucocorticoids increase with time. |