Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 3109443 | Interleukin-1 beta and interleukin-1 alpha stimulate the plasminogen activator activity an | 1987 May | Monocyte-macrophage polypeptides (monokines) cause synovial cells to increase the levels of putative mediators of destruction and inflammation. This interaction may account for some of the properties of rheumatoid pannus. We report here that samples of purified human interleukin-1 beta (IL-1 beta) and recombinant IL-1 alpha stimulate both the plasminogen activator activity and prostaglandin E2 levels of human synovial fibroblast-like cells. The same holds true for purified pig IL-1 (catabolin) and recombinant murine IL-1. The elevation in plasminogen activator activity was inhibited by indomethacin, and this suggests that endogenous prostanoids are important in the IL-1-mediated stimulation of proteinase activity. | |
| 2553025 | Suppression of human synovial cell proliferation by dihomo-gamma-linolenic acid. | 1989 Oct | Prostaglandin E1 (PGE1) and oils enriched in its precursor fatty acids suppress inflammation and joint tissue injury in several animal models. Since synovial cell proliferation is a hallmark of rheumatoid arthritis, we studied the effect of dihomo-gamma-linolenic acid (DGLA), an immediate precursor of PGE1, on the growth of human adherent synovial cells (ASC) in tissue culture. When stimulated by appropriate concentrations of recombinant interleukin-1 beta (rIL-1 beta), ASC proliferate and produce PGE. DGLA-enriched medium suppressed both baseline and rIL-1 beta-stimulated ASC growth fivefold, compared with medium supplemented with arachidonic acid. Indomethacin reduced the effect of the DGLA. Synovial cells incorporated the DGLA, and rIL-1 beta-stimulated cells that were incubated with DGLA exhibited a 14-fold increase in PGE1 (to 25.2 +/- 6.0 ng/ml, mean +/- SD) and a 70% decrease in PGE2 (to 25.2 +/- 4.2 ng/ml) compared with cells in control medium. At equivalent concentrations (5 x 10(-7) M), PGE1 increased the level of cellular cAMP to a greater extent than did PGE2 (16.8 +/- 2.0 pmoles versus 4.3 +/- 1.9 pmoles, mean +/- SEM). Exogenous PGE1 was also a more effective inhibitor of cell growth. Similarly, cAMP concentrations in cells exposed to DGLA for 6 hours were greater than concentrations in arachidonic acid-enriched cultures (17.8 +/- 3.3 pmoles versus 2.1 +/- 2.0 pmoles). These observations suggest that DGLA can restrain ASC growth, an effect which may be due to its capacity to increase PGE1 production and subsequent cellular cAMP concentration. | |
| 2542406 | Molecular characterization of a major autoantibody-associated cross-reactive idiotype in S | 1989 Jun 15 | Primary Sjogren's syndrome is an autoimmune disorder characterized by lymphocytic infiltration of the salivary and lacrimal glands, producing associated dry eyes (keratoconjunctivitis sicca), dry mouth, and intermittently swollen salivary glands. A high proportion of the infiltrating B lymphocytes express surface and cytoplasmic Ig bearing a kappa-L chain-associated CRI defined by reactivity with the murine mAb, 17.109. To determine the structural basis for CRI expression in this disease, we generated CRI+ lymphoblastoid cell lines and a cDNA library from lymphocytes extracted from Sjogren's syndrome patients' salivary gland biopsy specimens. Nucleic acid sequence analyses of the mRNA of one such 17.109-CRI+ lymphoblastoid cell line (NOV) reveals the expressed kappa light chain variable region gene (V kappa gene) to be homologous to Humkv325, a conserved V kappa gene used at relatively high frequency in certain B cell malignancies. In addition, synthetic oligonucleotides, corresponding to the first and third frameworks and the second complementarity determining region of the Humkv325 gene, were used to identify and isolate clones from a cDNA library generated from SS salivary gland lymphocytes. Clones annealing specifically with one or more of these oligonucleotide probes contained kappa light chain cDNA. The sequences corresponding to the variable region of two clones (Taykv320 and Taykv306) were homologous to Humkv325. The V kappa genes of four other cDNA clones (Taykv322, Taykv310, Taykv308, and Taykv312) most likely were generated somatically from the rearranged Humkv325 gene through a limited number of nucleic acid base substitutions. Our results suggest that the high frequency of 17.109-CRI expression in Sjogren's syndrome patients results from a multiclonal expansion of B cells using Humkv325, and that the expressed Humkv325 may undergo somatic diversification in an apparent Ag-driven response. | |
| 1708408 | Immunoglobulins within the central nervous system in primary Sjögren's syndrome. | 1990 Dec | Cerebrospinal fluid (CSF) and sera from 17 patients with primary Sjögren's syndrome (PSS) with or without clinical evidence of nervous system involvement were studied. Intrathecal IgG synthesis as measured by oligoclonal IgG bands on agarose isoelectric focusing or elevated IgG index in CSF was found in 6 of 8 patients with clinical nervous system involvement but also in 5 of 9 patients without clinical nervous system involvement. Elevated IgM-index in CSF was found in 7 of 8 patients with clinical nervous system involvement and in 6 of 9 patients without clinical nervous system involvement. By immunoblotting, CSF IgG-antibodies against myelin basic protein (MBP) were found in 3 of 12 patients with multiple sclerosis (MS), but in none of the patients with PSS or in the 12 controls. Intrathecal anti-viral IgG-antibodies, as measured by immunoblotting against measles, mumps, varicella or herpes simplex, were found in 8 of 17 patients with PSS, and in 7 of 12 patients with MS, but were not detected in the controls. Our observations support the concept that the central nervous system (CNS) is included in the multiple immunological phenomena of PSS. Interestingly, in some PSS patients intrathecal IgG synthesis occurred without overt clinical nervous system involvement and thus the clinical significance of intrathecal IgG synthesis in PSS is uncertain. The similarities with MS regarding intrathecal antiviral antibody production may be interpreted as the result of polyclonal B-cell activation. | |
| 3791713 | Immunohistochemical characterization of sialadenitis in NZB X NZW F1 mice. | 1987 Jan | The spontaneously developing sialadenitis in female autoimmune NZB X NZW F1 (NZB/W) mice has been studied with the help of immunohistochemistry and monoclonal antibodies to cell surface antigens. Semiquantitative assessment of stained cells within the infiltrates disclosed a progressive focal inflammation most pronounced in submandibular and parotid glands. The majority of cells expressed Ly-1 (all T cells) and L3T4 (T helper) phenotype, whereas only few Lyt-2 (cytotoxic/suppressor) expressing T cells were seen. A large proportion of the infiltrating cells stained for Ia antigens, which was also found on salivary gland ductal epithelium in the proximity of lymphoid infiltrates. The phenotypic pattern in sialadenitis of NZB/W mice thus closely resembles the pattern previously described for human Sjögren's syndrome (SS). Accordingly, immunomorphological analysis of the NZB/W sialadenitis may be useful in further studies of pathogenesis and therapy of both experimental and human SS. | |
| 1824252 | Inhibition of human erythroid colony-forming units by gamma interferon can be corrected by | 1991 Nov 15 | Tumor necrosis factor (TNF), interleukin-1 (IL-1), and gamma interferon (gamma IFN) inhibit erythropoiesis in vivo and in vitro, and have been implicated in the pathogenesis of the anemia of chronic disease. Anemia in patients with rheumatoid arthritis and in animals exposed chronically to IL-1 and TNF can be corrected by the administration of recombinant erythropoietin (Epo). We exposed highly purified human erythroid colony-forming units (CFU-E) cultured from peripheral blood burst-forming units-erythroid (BFU-E) and unpurified human marrow CFU-E to recombinant human gamma IFN and showed inhibition of colony formation in vitro. This inhibition was reversed by increased concentrations of Epo. The mechanisms by which this effect occurs are unknown at present. Epo may cause a downregulation of gamma IFN receptor expression on CFU-E or, alternatively, gamma IFN may cause a downregulation of Epo receptor expression. A full understanding of these mechanisms awaits a more complete comprehension of the regulation of erythropoiesis; however, the effect of Epo in vitro is similar to its ability to correct the anemia of chronic disease in vivo. | |
| 1826793 | Lymphocyte-selective cytostatic and immunosuppressive effects of mycophenolic acid in vitr | 1991 Feb | Mycophenolic acid (MPA), an inhibitor of inosine monophosphate dehydrogenase, in nanomolar concentrations blocks proliferative responses of cultured human, mouse and rat T lymphocytes and B lymphocytes to mitogens or in mixed lymphocyte reactions. The inhibitory effect of MPA on lymphocyte proliferation is reversed by addition to culture media of deoxyguanosine or guanosine but not by addition of deoxyadenosine or adenosine. The findings suggest that the principal mechanism of action of low concentrations of MPA is depletion of deoxyguanosine triphosphate which is required for DNA synthesis. In immunosuppressive doses, MPA does not affect the formation of IL-1 by LPS-activated human peripheral blood monocytes. Unlike cyclosporin A and FK-506, MPA does not inhibit the formation of IL-2 and the expression of the IL-2 receptor in mitogen-activated human T lymphocytes. MPA suppresses mixed lymphocyte reactions when added 3 days after their initiation. These findings suggest that MPA does not inhibit early responses of T and B lymphocytes to mitogenic or antigenic stimulation but blocks the cells at the time of DNA synthesis. The cytostatic effect of MPA is more potent on lymphocytes than on other cell types, such as fibroblasts and endothelial cells. MPA also inhibits antibody formation by polyclonally activated human B lymphocytes. MPA is an immunosuppressive agent reversibly inhibiting proliferation of T and B lymphocytes and antibody formation, with a profile of activity different from that of other immunosuppressive drugs. Human T and B lymphocytic and promonocytic cell lines are highly sensitive to the antiproliferative effects of MPA, whereas the erythroid precursor cell line K562 is less susceptible. The effect of MPA on cells of the monocyte-macrophage lineage could exert long-acting anti-inflammatory activity. MPA or analogues may have therapeutic utility in diseases such as rheumatoid arthritis, for prevention of allograft rejection and in lymphocytic or monocytic leukaemias and lymphomas. | |
| 2154410 | Regulation of c-fgr proto-oncogene expression in Epstein-Barr virus infected B-cell lines. | 1990 Feb 15 | We and others have previously shown that in vitro conversion of Epstein-Barr virus (EBV)-negative Burkitt lymphoma (BL) cell lines with the immortalizing B95-8 strain of EBV results in a marked elevation in levels of c-fgr proto-oncogene mRNA. We now show, using a nuclear run-off assay, that this induction results from an increase in the rate of transcription of the c-fgr gene. We also show that BL cell lines freshly converted with the non-immortalizing HR-I strain of EBV do not accumulate higher levels of c-fgr mRNA, suggesting that EBNA-2 and/or LMP, the genes which are deleted in the HR-I strain, may be involved in the pathway which leads to changes in c-fgr gene expression. In order to assess the generality of a role for the c-fgr gene in the response of B-lymphocytes to EBV-infection, which is controversial, we have analysed c-fgr expression in 6 freshly immortalized cell lines established by EBV (B95-8) infection of B-lymphocytes from the peripheral blood of normal adults and of adults with rheumatoid arthritis, from cord blood, and from foetal liver. All 6 cell lines expressed c-fgr mRNA at elevated levels compared to EBV-negative BL cell lines. | |
| 3044579 | Identification of a tumor-associated target antigen, ATM-1, for a human T-cell clone with | 1988 Sep 1 | Three human T-cell clones with activated killer activity (5B5, 5C1, and 7B5) which could lyse various tumor cell lines were established. The cytotoxic activity of these clones was decreased by incubation with anti-CD3 monoclonal antibody, suggesting that they recognized tumor cells by T-cell antigen receptor. A monoclonal antibody which blocked the cytotoxic activity of clone 5B5 was obtained. This antibody (N1977) blocked the binding and cytotoxic activity of clone 5B5 at the target cell level, suggesting that the antigen defined by N1977 antibody, designated as ATM-1, was a target molecule recognized by 5B5 cells. ATM-1 in the conditioned medium of a cancer cell line (NBT-2) and serum from a patient with lung cancer was characterized by following its immunoreactivity. On gel filtration, both the conditioned medium and the serum gave three peaks of ATM-1 immunoreactivity, corresponding to approximate molecular weights of 1,200,000, 700,000, and 120,000, respectively. They were chromatofocused at pH 4.0, 4.8, and 6.5, respectively. The high molecular weight forms were shown to be molecules with the disulfide-linked elementary glycoprotein with ATM-1 immunoreactivity and approximate molecular weight of 120,000. Most of the molecules with ATM-1 immunoreactivity bound to both concanavalin A and wheat germ agglutinin, and their binding activity to the antibodies was lost by treatment at 60 degrees C for 30 min. An assay of ATM-1 level in sera was performed by a sandwich enzyme immunoassay. The following positive percentages were obtained from preliminary clinical studies: breast cancer, 67% (8 of 12 cases); hepatocellular carcinoma, 83% (10 of 12 cases); gastric cancer, 58% (7 of 12 cases); lung cancer, 41% (5 of 12 cases); hematological malignancies, 0% (0 of 9 cases); systemic lupus erythematosus, 0% (0 of 8 cases); rheumatoid arthritis, 0% (0 of 8 cases). | |
| 2454027 | Piroxicam versus naproxen in the treatment of acute musculoskeletal disorders in athletes. | 1988 May 20 | Safe and effective therapy for acute musculoskeletal disorders would be extremely useful for competitive athletes. These injuries are common in these patients, who are usually highly motivated to return to their previous level of activity and performance. Because nonsteroidal anti-inflammatory drugs (NSAIDs) have been shown to be useful in inflammation-associated conditions such as rheumatoid arthritis and osteoarthritis, it was believed that their use in competitive athletes may be warranted. This study compared the efficacy and tolerability of two NSAIDs, piroxicam and naproxen, in these patients. The patients included 34 men and women who had acute symptoms including restrictions of movement and limitation of physical activity as a result of sprains to the ankle, acromioclavicular joint, and interphalangeal joint of the hand or acute soft-tissue injury to the shoulder, knee, or about the hip. In a double-blind, comparative, parallel manner, patients were randomly allocated to receive piroxicam 40 mg daily for two days and then 20 mg once daily, or naproxen 500 mg twice daily for two days, then 375 mg twice daily. Both drugs improved virtually all measures of physical discomfort after three and seven days of treatment (p less than 0.0001). Three days after beginning the study, the mean reduction in spontaneous pain, swelling, and tenderness was statistically superior in the piroxicam group (p less than 0.05) compared with the naproxen group. After seven days of treatment, a marginally larger reduction in swelling was associated with piroxicam (p = 0.081); however, no other statistically significant difference was seen. Although improvements in physical movement and strength were assessed, no consistent conclusion could be reached because of the small sample size; no statistically significant differences were seen between the treatment groups with respect to such improvements. Patient and investigator assessments of efficacy and tolerability were primarily excellent or good for both drugs. It was concluded that piroxicam and naproxen are effective and well-tolerated short-term treatments for acute musculoskeletal injuries in athletes. | |
| 2846506 | Chronobiology and asthma. III. Timing corticotherapy to biological rhythms to optimize tre | 1988 | Synthetic corticosteroids are frequently used to manage asthma and other inflammatory diseases. The timing of such drugs (whether ingested, inhaled, or infused) in relation to body rhythms influences the magnitude of both desired and undesired effects. It is crucial that corticotherapy be correctly scheduled to the circadian system of the hypothalamic-pituitary-adrenocortical (HPA) system. The secretion of cortisol from the adrenal cortex is not constant during each 24-hour period. Instead, production of this hormone varies as a high-amplitude circadian rhythm, with most of the secretion taking place during the initial hours of the activity span and very little late in the evening and during the first half of the sleep span. Results of laboratory and human studies indicate that the timing of exogenous corticosteroids, in relation to the circadian rhythm in HPA activity, is a critical factor. For example, the optimization of corticosteroid therapy for asthmatics entails daily (or alternate-day) administrations in the morning and, if necessary, early afternoon. By timing exogenous corticosteroids early during the activity span, the risk of adrenal suppression is minimized or avoided while bronchial patency is optimally enhanced, i.e., increasing the 24-hour average forced expiratory volume in 1 second (FEV1) and reducing its nocturnal dip. Clinical findings indicate that these results are obtainable with both acute and chronic corticosteroid therapies. In contrast, splitting the daily dose of corticosteroids into several small administrations, such as at mealtimes and before bedtime, markedly increases the likelihood of adrenal suppression without achieving the desired therapeutic effect. The dosing of synthetic corticosteroids late in the afternoon or evening, whatever the route of delivery, suppresses pituitary adrenocorticotropic hormone (ACTH) production during subsequent 24-hour spans, resulting in adrenocortical inhibition. Also, morning dosing of corticosteroids over many years seems to induce less--if any--osteopenia compared to dosing at other times. The adrenal response to exogenous administration of ACTH also is circadian-rhythmic. ACTH dosing in the morning results in greatest adrenal response in terms of cortisol secretion, while dosing in the evening results in least response. Knowledge of the circadian organization of the HPA axis is necessary to optimize the effect of synthetic corticosteroids, whether they be used to treat asthma, rheumatoid arthritis or other cortico-dependent diseases, or as a substitution therapy for Addison's disease. | |
| 2953314 | HLA-DR4 and Gm(1,3;5,21) are associated with U1-nRNP antibody positive connective tissue d | 1987 Mar | Patients with U1-nRNP antibodies (n = 35, 31 female, four male) were typed for HLA-A, -B, -C, and -DR antigens and IgG heavy chain allotypes G1m(1), -(2), -(3), G3m(5), and -(21). The patient group was clinically heterogeneous. Four met the American Rheumatism Association criteria for systemic lupus erythematosus, six for progressive scleroderma, and 14 for rheumatoid arthritis. Sicca syndrome was present in seven cases. Twenty three had overlapping features compatible with mixed connective tissue disease (MCTD). Healthy blood donors served as controls for HLA typing (n = 64), Gm typing (n = 228), or both (n = 56). Sixty six per cent of the patients with U1-nRNP antibodies were DR4 positive compared with 28% of the controls (relative risk = 4.9, p = 0.00053). The Gm(1,3;5,21) phenotype was found in 46% of the patients and 25% of the controls (relative risk = 2.47, p = 0.0247). Within the patient group Gm(1,3;5,21) was found only in DR4 positive individuals. The coincidence of HLA-DR4 and Gm(1,3;5,21) increases the relative risk values to 8.0 (compared with the group with neither risk factor). DR4 and Gm(1,3;5,21) primarily seem to be related to U1-nRNP antibody formation and not to disease expression. Patients with or without MCTD did not differ with respect to DR4 or Gm(1,3;5,21) frequency. Disease onset was earlier in patients with HLA-DR4/Gm(1,3;5,21) than in patients without both markers (mean 27.9 v 40.1 years; p less than 0.05). | |
| 1909258 | Seroprevalence of antibody against hepatitis C virus (anti-HCV) in various groups of indiv | 1991 Jul | We studied the prevalence of anti-HCV in 585 sera from various individuals, using enzyme immunoassay (EIA, Abbott Lab.). Anti-HCV was detected in 16 (10.7%) out of the 150 patients with HBsAg positive liver diseases diagnosed by liver biopsy and they consisted of none out of 10 acute viral hepatitis, 3 out of 15 chronic persistent hepatitis, 4 out of 50 chronic active hepatitis, 2 out of 32 liver cirrhosis, and 7 out of 43 hepatocellular carcinoma. Anti-HCV was detected in 43 (45.3%) out of 95 patients with HBsAg negative liver diseases diagnosed by liver biopsy and they consisted of 5 out of 8 acute viral hepatitis, 2 out of 10 chronic persistent hepatitis, 17 out of 30 chronic active hepatitis, 4 out of 15 liver cirrhosis, and 15 out of 32 hepatocellular carcinoma. Anti-HCV was detected in 22 (38.6%) out of 57 hemodialysis patients, in 3 (6.7%) out of 45 kidney transplants, in 2 (11.1%) out of 18 fatty liver diagnosed by liver biopsy, in 2 (1.3%) out of 150 healthy blood donors, in none out of 40 healthy volunteers, in 6 (31.6%) out of 19 rheumatoid arthritis and in 6 (54.5%) out of 11 systemic lupus erythematosis cases. There were familial clusters of chronic liver diseases in 4.7% of patients with HBsAg negative/anti-HCV positive chronic liver diseases, while in 19.4% of patients with HBsAg positive/anti-HCV negative liver diseases. Incidence of anti-HCV within patients with HBsAg positive liver diseases was higher in HBsAg negative patients than in HBsAg positive patients (17.6% and 10.3%, respectively).(ABSTRACT TRUNCATED AT 250 WORDS) | |
| 1906383 | Effects of granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-2, interferon-gam | 1991 Jul | The effects of GM-CSF, IL-2, IFN-gamma, TNF-alpha and IL-6 on the production of IL-1 (both secreted and cell associated) and TNF-alpha by peripheral blood monocytes were studied. Monocytes were cultured for 20 h in suspension and in serum-free conditions which minimized background stimulation of monokine production. GM-CSF, IL-2 and TNF-alpha directly induced the production of cell-associated IL-1 but little or no IL-1 or TNF-alpha secretion. Combination of GM-CSF with IFN-gamma, IL-2 or TNF-alpha synergistically enhanced IL-1 secretion and had an additive effect on cell-associated IL-1 production. Combination of IL-2 with IFN-gamma or TNF-alpha also synergistically enhanced IL-1 secretion but the effect on cell-associated IL-1 production was less than additive. GM-CSF synergistically enhanced TNF-alpha secretion induced by IFN-gamma but not by lipopolysaccharide. GM-CSF did not enhance TNF-alpha secretion induced by IL-2 or TNF-alpha. In contrast, IL-2 synergistically enhanced TNF-alpha secretion induced by IFN-gamma. These results are discussed in relation to cytokine involvement in rheumatoid arthritis. | |
| 1785666 | Erythropoietin. Biology and clinical applications. | 1991 Winter | Erythropoietin is a glycoprotein hormone that plays a vital role in erythropoiesis. It is mainly produced in the fetal liver till the third trimester of pregnancy. At that point, the kidney interstitium takes over this function and becomes the main source of erythropoietin. Hypoxia stimulates erythropoietin production by a mechanism that may require a heme protein as a second messenger. Erythropoietin stimulates the maturation of erythroid precursors (colony-forming unit-erythroid and burst-forming unit-erythroid) via at least two types of cell surface receptors. The higher-affinity receptors appear to be more important in modulating the effects of erythropoietin in vivo. Changes in intracellular calcium may ultimately mediate the action of erythropoietin on erythroid precursors. A specific and sensitive radioimmunoassay is now available for accurately measuring erythropoietin levels. All forms of erythrocytosis except polycythemia vera are associated with elevated erythropoietin levels. Levels are also high in cord blood obtained following fetal asphyxia. Reduced levels are seen in patients with anemia due to renal diseases. The response of erythropoietin to the degree of anemia appears to be attenuated in patients with cancer, chronic diseases, and human immunodeficiency virus (HIV) infection. Erythropoietin has been successfully used for treating patients with anemia due to renal failure. Its use has also been approved for the treatment of anemia patients receiving zidovudine for HIV infection. Encouraging results have been observed when erythropoietin was used to treat anemia due to rheumatoid arthritis, hematological malignancies, and prematurity. It has also been used to increase the yield of autologous blood collected prior to an elective surgical procedure. However, it has not proved to be useful in sickle cell anemia and myelodysplastic syndromes. | |
| 1759731 | [Glycoforms of serum alpha 1-antichymotrypsin studied by immunoaffino-electrophoresis. Fro | 1991 | alpha 1-antichymotrypsin, purified or in whole serum, exhibits microheterogeneous forms when studied by crossed immunoaffinoelectrophoresis with free concanavalin A (Con A) in the first dimension. alpha 1-antichymotrypsin purified from the serum of a single healthy donor was separated into three forms by affinity chromatography on a Con A-Sepharose 4B column: a Con A non-reactive form, a Con A weakly reactive form and a Con A reactive form. Some of their physico-chemical properties are compared. The complete primary structure of the glycans of each form was determined by high resolution 1H-NMR spectroscopy. The results indicated the presence of diantennary and triantennary type glycanic structures which occur frequently in serum glycoproteins. From deglycosylation experiments it is concluded that alpha 1-antichymotrypsin carries four oligosaccharide side chains. The Con A non-reactive form contains four triantennary glycans, the weakly reactive form contains three triantennary and one diantennary glycans and the Con A reactive form possesses on average one triantennary and three diantennary glycans. Significant variations in the relative ratios of the microheterogeneous forms were detected in various inflammatory syndromes. There is an increased proportion of Con A non-reactive form in patients developing a systemic disease (systemic lupus erythematosus, rheumatoid arthritis, temporal arteritis). In contrast, the proportion of Con A non-reactive form decreased in patients with acute septic inflammation whereas no variation appeared in patients with metastatic breast cancer. We also studied the variations of alpha 1-antichymotrypsin microheterogeneity in sera from patients with giant-cell arteritis and/or polymyalgia rheumatica before and during treatment with glucocorticoids.(ABSTRACT TRUNCATED AT 250 WORDS) | |
| 1966582 | Normal suppressive T cell function of Epstein-Barr virus induced B cell activation in type | 1990 | Several studies have demonstrated abnormalities of T cell regulation of Epstein-Barr virus-induced B cell activation in systemic autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematous, and systemic sclerosis. However, a normal suppressive peripheral T cell function was observed in Graves' disease. To investigate whether this abnormality is a common feature to other autoimmune diseases, we studied T cell regulation of Epstein-Barr virus induced B cell activation in 15 newly diagnosed type 1 (insulin dependent) diabetes mellitus patients and 10 normal control subjects. Peripheral B lymphocytes infected with Epstein-Barr virus were cultured for 20 days in the presence or absence of autologous T cells at different ratios (1:1 and 1:4). IgM and IgG secretions into the supernatants were determined using an enzyme-linked immunosorbent assay. The extent of suppression when T cells were added, as measured by a suppression ratio, was not significantly different in type 1 (insulin dependent) diabetes mellitus patients and normal subjects. We conclude that in type 1 (insulin dependent) diabetes mellitus, the autoimmune reactivity is not dependent upon a generalized suppression defect. It can be hypothesized, therefore, that in type 1 diabetes mellitus as well as in Graves' disease, a local or organ specific suppressor deficit may induce the autoimmune phenomena. | |
| 2788486 | Clinical manifestations of HLA-B27-positive acute anterior uveitis in Chinese. | 1989 Feb | One hundred and seventeen consecutively detected Chinese patients, 100 males and 17 females, with HLA-B27-Positive acute anterior uveitis (AAU) were studied in the uveitis clinic at the National Yang-Ming Medical College and Veterans General Hospital during a 3-year period from January 1984 to December 1986. The ages of onset of uveitis ranged from 8 to 76 years and averaged 38.2, with most of them (63.8%) distributed between 30 and 59 years and a peak incidence in the thirties. Of the 137 uveitis attacks observed during the follow-up, 60.6% manifested as serous iridocyclitis and 39.4% highly fibrinous. Mutton-fat keratic precipitates were never noted. Of the 117 patients, 78 (66.7%) had recurrent uveitis attacks. The average interval between successive attacks was longer than 1.5 years in 50 (64.1%) of the 78 patients. All patients were unilaterally involved in an AAU attack. Of the 78 patients with recurrent uveitis attacks, 25.6% had an ipsilateral eye suffering from uveitis attacks and 74.4% had uveitis attacks involving either eye. In viewing the distribution of AAU attacks, a significant monthly variation was found (p less than 0.0001) with the highest incidence from December to March. Posterior synechiae and cataract were the most common two persistent ocular complications, which were present in 31.4% and 14.3% of the diseased eyes respectively. The visual prognosis was generally good with 90.3% of the diseased eyes having a visual acuity better than 0.5.2+ Among the 117 patients, 75.2% had an association with seronegative spondylarthropathies, which included ankylosing spondylitis (50.4%), probable ankylosing spondylitis (6.8%), Reiter's disease (12.0%), juvenile rheumatoid arthritis (4.3%) and psoriatic arthropathy (1.7%).(ABSTRACT TRUNCATED AT 250 WORDS) | |
| 3485459 | T cell receptor gene rearrangements define a monoclonal T cell proliferation in patients w | 1986 Apr | We have used probes from the T cell receptor beta and gamma chain loci to investigate the clonality of T lymphocytes in eight patients with T cell lymphocytosis and cytopenia (TCLC). This syndrome, which is strongly associated with rheumatoid arthritis, is characterized by peripheral blood and bone marrow lymphocytosis and neutropenia, red cell aplasia, or both. By means of T cell monoclonal antibodies and flow cytometry, T lymphocytes from patients with this syndrome have been shown to have characteristic immunologic features. Investigators have disagreed as to whether the syndrome represents a T cell malignancy or a more benign immunologic disorder. DNA from five of five patients with symptomatic "classic" T cell lymphocytosis with cytopenia demonstrated unique rearrangements of the T cell receptor beta chain locus, whereas neither of two patients with atypical features showed rearrangement. In addition, we found evidence for gamma chain rearrangement in those DNAs with clonal beta chain rearrangement. We thus postulate that the classic form of this syndrome is associated with a monoclonal proliferation of T cells. Its potential relationship to T cell chronic lymphocytic leukemia is discussed. | |
| 2418442 | Human T-cell clones used to define functional epitopes on HLA class II molecules. | 1986 Feb | Polyclonal reagents have been used to define HLA class II molecules in conventional serologic and cellular typing. We generated human alloreactive T-cell clones to analyze the functional fine specificities of HLA class II molecules that might be important for the phenomenon of HLA and disease association. We chose to examine HLA-Dw14, an HLA-D specificity that has been associated with juvenile rheumatoid arthritis. In this paper we have presented data that suggest that conventional cellular typing does not reflect the distribution of T-cell epitopes on major histocompatibility complex class II molecules. We describe three alloreactive T-cell clones that have defined three separate Dw14-associated T-cell epitopes. Two of these epitopes were on a DR-region molecule; the third was located on a DQ-region product. In a panel of unrelated DR4-positive donors, these three DW14-associated determinants were present in a high frequency but were not linked to each other. Within the tested panel of DR4-positive cells, all possible combinatorial arrangements of these three allodeterminants were seen. The concurrent expression of any two of the three allodeterminants was equivalent to a positive typing response for Dw14. Our finding that HLA-Dw14 is not characterized by a unique allodeterminant but by the combinatorial recognition of independently distributed T-cell interaction sites suggests that analysis of HLA and disease association may be more clearly demonstrated through the use of human T-cell clones. |