Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 229892 | Covalent structure of collagen: amino acid sequence of alpha 2-CB5 of chick skin collagen | 1979 Nov 27 | The amino acid sequence of the 112 residues from the amino terminus of alpha 2-CB5 from chick skin collagen was determined by automated sequential degradation of intact alpha 2-CB5 and several chymotryptic and tryptic peptides. This segment of the peptide includes the site of the action of animal collagenases. As compared to the sequence around the alpha 1 cleavage site, the alpha 2 sequence is notable for the remarkable constancy of the residues to the amino side and the relative abundance of hydrophobic residues to the carboxyl side of the cleavage site, suggesting that these features are important in the recognition by the enzyme. The sequence of this region of the alpha 2 chain is consistent with the Gly-X-Y triplet structure and the preference of certain residues for either the X or Y position in distribution. However, three of the six residues of leucine were found in the Y position rather than the X position. Leucine residues were found only once in the Y position in the alpha 1 (I) chain. This preference does not appear to hold in the alpha 2 chain. | |
| 417620 | Screening test for complement activation by counterimmunoelectrophoresis. | 1978 Apr | This report describes the use of counterimmunoelectrophoresis (CIE) as a method of detecting activation of the complement system. With this technic small amounts of C3 split products (C3c/d) can be detected in plasma samples by specific precipitation with antiserum in less than two hours. The CIE technic is a highly sensitive, rapid method for detecting activation of the complement system in the presence of normal concentrations of C3 measured hemolytically or by radial immunodiffusion (RID) in human disease. A clinical investigation was carried out in 40 patients with systemic rheumatic diseases and 116 normal healthy individuals. The following observations were made: (1) plasmas and sera from normal individuals had normal total complement hemolytic activity (CH50), hemolytic active C4 (C4H50) and C3 (C3H50); (2) in 30% of the serum samples it was possible to identify the presence of C3 split products, in contrast to only 2.5% of the plasma samples obtained simultaneously; (3) in the specimens from patients who had rheumatic disease activity, C3 split products were identified by CIE in all cases except one in the presence of normal C3 protein measured by RID. | |
| 3158395 | Immunobiological function of normal rabbit synovial cells. | 1985 Apr 1 | The ability of enzyme-dissociated primary cultures of synovial cells (Sy) to present antigen was investigated. Adult rabbits were immunized in foot pads with bovine serum albumin (BSA) in complete Freund's adjuvant (CFA) or with CFA alone. Four to six weeks later draining popliteal lymph node cells (LNC) and synovial cells were obtained. Synovial cells were cultured overnight with or without antigen. About 20% of these synovial cells had Fc receptors and 15% C3 receptors. As a positive control splenic adherent cells (SAC) were similarly treated. Next day, autologous lymph node cells were added to the extensively washed and irradiated synovial cells or splenic adherent cells. Lymphocyte proliferation was measured by [3H]thymidine uptake. Synovial cells as well as splenic adherent cells induced mixed lymphocyte reaction (MLR) and autologous mixed lymphocyte reaction (AMLR) and effectively presented antigen for specific immune response to the priming antigen. Thus, the synovium contains macrophage-like cells that can effectively interact with lymphocytes and participate in the immune phenomena in the joints of patients with rheumatoid arthritis. | |
| 6749105 | [Serum levels of immunosuppressive acidic protein (IAP) in various disease states and thei | 1984 Apr | The IAP level of sera from normal subjects and patients with various diseases were quantitatively measured by single radial immunodiffusion method. The mean IAP concentration in the sera from 152 normal individuals was 375.3 +/- 100.1 micrograms/ml, whereas among 86 patients with benign diseases, the level in 26 patients with acute abdominal inflammation or rheumatoid arthritis was particularly higher than normal level. The IAP level in 277 patients with carcinoma was 642.9 +/- 311.0 micrograms/ml which carcinoma was about 2-hold higher than normal level, especially in the patient with lung, biliary tract and esophageal cancer. Following successful surgical resection of carcinoma, the IAP level gradually decreased to normal level, but in the recurrent cancer patients the level increased markedly again. The changes of IAP level was quantitatively correlated with the serum level of alpha 1-acid glycoprotein (alpha 1-AG). However, IAP level had relatively higher response more than that of alpha 1-AG in patients with inflammation and carcinoma. In gastric cancer patients, there was a good correlation between IAP in increased level and phytohemagglutinin response in peripheral lymphocytes. The evidence suggests that IAP level is a good immunological marker, which is associated with the tumor progression, recurrent involvement and effectiveness of therapeutic programs. | |
| 6127059 | Hepatitis B virus infection in patients with rheumatic diseases. | 1982 Oct | Two hundred and thirty-nine patients with different rheumatic diseases were investigated for serological markers of hepatitis B virus (HBV) infection. An increased prevalence of anti-HBs was found in patients with systemic lupus erythematosus. The total prevalence of HBV markers in patients with polymyalgia rheumatica, temporal arteritis, juvenile and adult rheumatoid arthritis (RA) and systemic sclerosis was not significantly different from age-matched controls. Remarkably, 6 patients were HBsAg-positive of whom 3 had RA (4%). Two patients with RA were "healthy' HBsAg carriers. The third patient had circulating HBeAg as well and had shown progression from acute hepatitis to cirrhosis during the time of observation. Three of 18 patients with polyarteritis nodosa were HBsAg- and HBeAg-positive, and all 3 were young men. Clinical improvement was seen in one of these patients and was associated with seroconversion from HBeAg to anti-HBe. Our data do not support the theory that HBV is an aetiological factor in rheumatic diseases except in some cases of polyarteritis nodosa. | |
| 3885680 | Anti-DNA antibodies: the choice of assays for routine diagnostic work. | 1985 Feb | Sixty-six sera from 23 patients with systemic lupus erythematosus (SLE), 26 sera from patients with rheumatoid arthritis (RA), and 22 sera from normal healthy subjects were tested for the presence of antibodies against native (ds) DNA by the Crithidia luciliae immunofluorescence test and by the Farr assay, and for the presence of antibodies against denaturated (ss) DNA by the enzyme-linked immunosorbent assay (ELISA). Anti-dsDNA antibodies were detected in 57% of the SLE patients by the Crithidia test and in 65% by the Farr assay. Two of the RA sera were positive in the Crithidia test, whereas all were Farr negative. Anti-ssDNA antibodies of IgG class could be detected in 74% of the SLE patients and in none of the RA sera, while anti-ssDNA antibodies of IgM class were found in 26% of the SLE patients and in one RA serum. There was a good correlation between the results of the Farr assay and the IgG-anti-ssDNA ELISA but no agreement was found between the results of the Farr assay and the Crithidia test. We also measured the amount of C-reactive protein (CRP) in the sera but no correlation was seen between the levels of CRP and anti-DNA antibodies. We conclude that the demonstration of anti-ssDNA antibodies of IgG class is a good screening method in the diagnosis of SLE, and that antibodies against native DNA should be determined, preferably both by the Crithidia test and the Farr assay to confirm the diagnosis and in the follow-up of the patients. | |
| 394274 | The value and results of long-term studies with diclofenac sodium (Voltarol). | 1979 | The results of 940 patients treated with diclofenac for 3 to 24 months in comparative and non-comparative trials are presented. Maximal improvement tended to occur in the first 3 to 6 months of treatment and was generally maintained. Diclofenac was at least as effective as equivalent doses of indomethacin and naproxen and, when treatment lasts more than 3 months, may be more effective. The majority of patients reporting unwanted effects or discontinuing treatment did so in the first 6 months. Unwanted effects (similar to those in short-term trials) were mainly gastrointestinal. Central nervous system, cardiovascular and dermatological side-effects were reported in 1% or less of patients. The long-term laboratory tolerability of diclofenac was good, with no changes in the nature, frequency or severity of abnormal tests with increasing duration of treatment. During the development of diclofenac sodium (Voltarol) various types of long-term investigation were conducted (Table I). This paper presents the results, covering a total of 940 patients treated for 3-24 months, and discusses their significance. | |
| 6983963 | Autoimmune reactions and rheumatoid arthritis. | 1982 | The reviewed data suggest with a high degree of certainty that IgG and IgG antibodies in immune complexes as well as native and denatured collagen type I, II, and III are autoantigens capable of inducing T cell activation in patients with RA. Proteoglycans and their derivatives seem to modify lymphocyte reactions in a largely non-specific way and their potential to activate T Lymphocytes in RA has still to be confirmed. The occurrence of activation products of T lymphocytes in synovial tissue incubates and synovial fluid of RA patients that is of lymphokines seems to be established. The major autoantibody synthesized by synovial tissue (ST) of seropositive and seronegative RA and juvenile RA patients is IgG- rheumatoid factor (RF) and in seropositive adult cases in addition IgM-Rf. Synthesis of various types of agglutinators by ST plasma cells of adult and juvenile RA patients is a distinct but less prominent feature--than synthesis of Rf. In addition indirect evidence suggests that RA-ST synthesizes to some degree antibodies directed against native and denatured collagen type I/II/III and antibodies directed against different nuclear antigens as well as immunoconglutinin. All these autoantibodies seem to participate in the immune complex formation in RA joints and to activate the complement system. The vast majority of immune complexes, however, consists of IgG-Rf/IgG antigen and--in seropositive RA--of IgM-Rf. | |
| 1135610 | Hydroxyproline levels and collagenolytic activity in synovial fluids of patients with rheu | 1975 | Free, total, and peptide hydroxyproline levels were determined in synovial fluid obtained from the knee joints of 60 patients with theumatoid arthritis (RA), and 26 patients with degenerative joint disease. In addition, in 160 synovial fluid samples obtained from 121 patients including 50 with degenerative joint disease, 60 with RA, 3 with Reiter's syndrome, 3 with hydarthrosis intermittens and 5 with ankylosing spondylitis, the collagenolytic activity was determined. The mean values of free and peptide hydroxyproline in the inflammatory and degenerative fluids were the same, but slight differences were found in the mean values of total hydroxyproline. No effect on the level of free and bound hydroxyproline was observed after treatment with intra-articular hydrocortisone and gold salts. The collagenolytic activity of synovial fluid was registered in 38% of cases of RA and in some cases of Reiter's syndrome and hydrarthrosis intermittens, but it was not found in 50 cases of degenerative joint disease or in cases of ankylosing spondylitis. During a longer observation of patients with inflammatory forms of RA a variability in the collagenolytic activity was observed in repeated examinations of the fluid obtained from the same patient; this activity appeared and disappeared. The incidence of collagenolytic activity and its values were higher in patients with active rheumatoid process and this activity was present more frequently in patients with a short history of the disease (up to 3 years). The collagenolytic activity of rheumatoid fluids was, to a high degree, inhibited by normal human serum. The problem of presence or lack of collagenolytic activity in rheumatoid fluids is discussed. | |
| 6977573 | Circulating autoantibodies to IgD in rheumatic diseases. | 1982 Apr | Most mature B lymphocytes possess IgD on their cell surface. Antibodies to IgD produce an adjuvant-like effect in many experimental systems. Employing sensitive class-specific radioimmunoassays, elevated concentrations of autoantibodies to IgD of the IgA, IgM, and IgG classes were detected in the sera of 55% of patients with adult onset rheumatoid arthritis (RA), of 45% with systemic lupus erythematosus (SLE), of 67% with mixed connective tissue disease syndrome (MCTD), and of only 8% of juvenile RA. Marked differences in the class of anti-IgD were noted. An elevated IgA anti-IgD was detected in 45% (p less than 0.01) of RA sera, 27% of SLE sera, and 58% (p less than 0.01) of MCTD sera. IgG anti-IgD was increased in only 26% of RA, 32% of SLE, and 8% of MCTD sera. IgM anti-IgD was elevated in only one patient. IgA anti-IgD was inhibited greater than 90% by IgD but not at all by IgG. Correlations between the concentration of immunoglobulin G and IgA anti-IgD were noted in RA (rs = 0.37, p = 0.02), SLE (rs = 0.46, p = 0.015), and MCTD (rs = 0.4). These data suggest a potential role for autoantibodies to cell surface IgD as modulators of the immune system in some patients with autoimmune disorders. | |
| 1114048 | Technetium-99m polyphosphate bone image for early detection of skeletal metastasis. Correl | 1975 Jan 31 | Technetium 99m-polyphosphate bone images are correlated with bone roentgenography, and serum calcium, phosphorus and alkaline phosphatase in 91 patients with suspected bone metastasis. Technetium polyphosphate bone images are the most sensitive and serum level of calcium and phosphorus are the least sensitive indicator of bone lesions. Bone roentgenography is not as sensitive as technetium polyphosphate images. Abnormal bone images with normal or abnormal bone roentenography associated with increased alkaline phosphatase in the absence of liver metastasis are highly suggestive of metastatic bone disease. Abnormal bone images adjoining the joints, associated with normal serum alkaline phosphatase and abnormal joint roentgenography suggest arthritis. It is recommended that technetium 99m-labelled phosphate bone images are considered to be the diagnostic procedure of choice to detect skeletal lesions. Polyphosphate bone images are highly sensitive, with the combination of elevated alkaline phosphatase they become relatively more specific for a metastatic bone disease. | |
| 6983711 | In vitro synthesis of immunoglobulins and IgM-rheumatoid factor by blood mononuclear cells | 1982 | In vitro synthesis of IgG, IgM and IgM-rheumatoid factor (IgM-RF) was investigated in unstimulated and pokeweed mitogen (PWM)-stimulated 7-day cultures of blood mononuclear cells (BMC) from 28 seropositive patients with active rheumatoid arthritis (RA), in a second group of 13-day cultures from 94 unselected rheumatoid patients, and in 21 healthy controls. Both normal and rheumatoid BMC cultures synthesized IgM-RF in response to PWM stimulation. Mitogen-induced stimulation was shown to be dependent on the presence of T-lymphocytes. PWM-induced IgM and IgM-RF synthesis were reduced in BMC from rheumatoid patients in comparison with healthy controls. However, the fraction of IgM-RF in the total IgM synthesized was significantly higher in the RA supernatants than in the controls, suggesting the presence of a larger precursor B-cell population committed to IgM-RF synthesis in those cultures. BMC from 44 of the 94 patients demonstrated spontaneous synthesis of IgM-RF, and this was positively correlated with disease activity and rheumatoid factor titer. Spontaneous production was shown to reside in the T-lymphocyte depleted, adherent cell-depleted, B-cell subpopulation. It is concluded that in active RA there is a specific activation and expansion of the circulating B-cell subpopulation committed to IgM-RF synthesis, possibly due to abnormal immunoregulatory mechanisms modulating synthesis of this antibody. | |
| 275517 | Acute leukemia following cyclophosphamide therapy for Sjögren's syndrome. | 1978 Jun | A fatal myeloproliferative syndrome diagnosed as subacute myelomonocytic leukemia developed in a patient with Sjögren's syndrome following treatment with cyclophosphamide. Although patients with Sjögren's syndrome have a recognized increased risk of developing lymphoproliferative disorders, particularly reticulum cell sarcoma, there is no evidence to support a similar predisposition to leukemia. As immunosuppressive therapy is becoming more common in the treatment of patients with rheumatoid arthritis, there have been recent reports of patients developing fatal myeloproliferative disorders after receiving immunosuppressive therapy. Review of these cases shows similar duration of therapy, and cyclophosphamide, among others, has been implicated as the leukemogenic agent in other patients. We feel that great caution should be exercised in the use of immunosuppressive drugs in patients with chronic, nonfatal disorders sich as rheumatoid arthritis and Sjögren's syndrome. | |
| 790556 | Symptomatology and diagnosis in connective tissue disease. Antibodies to extractable ribon | 1976 | Sera with an antinuclear immunofluorescence titre of 1/000 were taken consecutively from the diagnostic routine flow and examined for agglutinating antibodies against desoxyribonucleic acid (DNA) and extractable nuclear antigens (ENA). Passive haemagglutination tests with antigen-coated tanned erythrocytes were used and the specificity of the reactions was corroborated by testing against enzyme-treated cells. After the exclusion of the DNA-reacting 15%, three major groups and one minor could be distinguished on a serological basis. The largest group (41%) contained cases with a speckled immunofluorescence pattern and a RNase-trypsin sensitive agglutination reaction with ENA coated cells (sRNP). Nearly all cases of mixed connective tissue disease and scleroderma fell into this group which also contained 44% of the SLE cases. Symptomatically the group was characterized by remarkably high incidences of Raynaud's syndrome and myositis. The major group next in size comprised cases with a homogeneous immunofluorescence pattern but no reaction against DNA or ENA. Half of the cases within this group had the diagnosis SLE; they also constituted 42% of all SLE cases. The only other diagnosis of significant frequency within the group was unspecified collagenosis (23%). The symptomatology of the group was rather uncharacteristic, with the exception of the low incidence of Raynaud's syndrome. The third major group comprised cases with a speckled immunofluorescence pattern but no agglutination reaction against ENA or DNA. This group had a very high incidence of rheumatoid factor and also the highest incidence of visceral lesions among the groups. Yet the group contained only a small proportion (14%) of the SLE cases and the rheumatoid arthritis cases were about equally shared between this and the first group. The most common diagnosis in the group was unspecified collagenosis (40%). A fourth, small but homogeneous group contained cases with a speckled immunofluorescence pattern and a reaction with Sm antigen, i.e. an enzyme-resistant agglutination reaction with ENA. Six cases in this group had the diagnosis SLE. No diagnosis was available in two cases. | |
| 6426053 | Is gold necessary in so called chrysotherapy? | 1983 | It is postulated that the efficacy of sodium aurothiomalate and d-penicillamine could be partly dependent on the activity of sulphydryl groups. Free thiomalate, the thiol from sodium aurothiomalate was shown to be liberated in vivo and has been detected in the blood and urine of sodium aurothiomalate-treated patients. An increase in intracellular glutathione levels in response to treatment with sodium aurothiomalate and penicillamine was demonstrated and considered to be related to these drugs' properties as thiols. A pilot clinical trial using sodium thiomalate treatment demonstrated clinical improvement in four out of six patients after one course. Two patients relapsed but both improved after a second course and there were no serious adverse reactions. It is concluded that although larger controlled clinical trials are required, the role of gold in "chrysotherapy" must remain in question. | |
| 444667 | In vitro cytotoxic response to human myeloma plasma cells by peripheral blood leukocytes f | 1979 Jul | Peripheral blood leukocytes (PBL) from myeloma patients were studied for their capacity to lyse plasma cells from myeloma patients, benign monoclonal gammopathy (BMG) patients, and nonneoplastic disease patients. Plasma cells were isolated from bone marrow, labeled with 51Cr, and cultured with PBL isolated from patients with myeloma, BMG, or nonneoplastic disease, as well as normal individuals. PBL from patients with multiple myeloma demonstrated responses to autologous or allogeneic myeloma plasma cells. Optimum conditions for cytotoxic response included a responder-to-stimulator ratio of 1:1 and an effector-to-target ratio of 20:1. PBL from normal individuals or patients with BMG failed to demonstrate this response. However, PBL from BMG patients, but not normal individuals, could be induced to kill myeloma plasma cells (but not nonmyeloma plasma cells) by simultaneous stimulation with allogeneic lymphocytes and myeloma plasma cells. | |
| 6321722 | Cellular interactions and control of collagenase secretion in the synovium. | 1983 Dec | Monocyte/macrophages release a factor, mononuclear cell factor (MCF), homologous with interleukin 1 (IL-1), which augments synthesis and release of collagenase and prostaglandins by connective tissue cells such as synovial cells and chondrocytes. The production of MCF is increased by interactions with immunoglobulins, collagens, and T lymphocytes. Human U937 cells, which behave as immature monocytes, do not produce MCF unless induced by a soluble product of activated T lymphocytes. Induction of MCF is augmented by 1,25-dihydroxyvitamin D. This cell culture system serves as a model for aspects of joint inflammation. | |
| 382939 | UCLA conference. Circulating immune complexes: their immunochemistry, detection, and impor | 1979 Sep | The size and molecular composition of circulating immune complexes depend on various factors, including the concentrations and valences of antigens and antibodies and the antigen-antibody ratio. The composition and biological properties of circulating immune complexes, in turn, influence their fate in vivo as well as the likelihood of their detection by various assays. Several assays clearly detect circulating immune complexes, but no single assay has yet been shown to be the most sensitive and the most specific for the entire spectrum of circulating immune complexes. Assays correlate poorly with each other, but this may be desirable if we are to determine which circulating immune complexes have diagnostic, prognostic, or pathogenic importance. Circulating immune complexes are found in numerous rheumatologic disorders and infectious diseases. Their presence in the circulation statistically correlates with disease activity; however, the assays currently used have limited value for diagnosing or aiding in therapeutic decisions. Nevertheless, the future holds promise for such uses. | |
| 6347489 | In vitro immunoglobulin production by mononuclear cells in rheumatoid arthritis. | 1983 Aug | Since patients with rheumatoid arthritis (RA) exhibit serum hypergammaglobulinemia and autoantibody (rheumatoid factor) production, we compared elaboration and control of in vitro RA mononuclear cell (MNC), Ig assayed by enzyme-linked immunoassays or by hemolytic plaque formation, in 37 RA patients and 17 normal subjects. We found (1) RA spontaneous plaque-forming cells were significantly reduced (RA 344 vs normal 627 PFC/10(6) MNC, P less than 0.002); (2) RA spontaneous IgG and IgM (but not IgA) elaboration was significantly diminished (IgG RA 339, normal 776; IgM RA 255, normal 869 ng/ml, P less than 0.001; IgA RA 87, normal 124); (3) RA stimulated IgG and IgM production (but not IgA) was also decreased (IgG RA 2434, normal 3862, P less than 0.06; IgM RA, 1676, normal 3323, P less than 0.005; IgA RA 1859, normal 2315); (4) reduced RA Ig elaboration was not clearly due to altered numbers of T or non-T cells, age, medications, clinical features of disease, or response kinetics; (5) relative improvement of RA in vitro IgG, but not usually IgM, secretion followed removal of adherent cells, addition of indomethacin or addition of mitomycin C-treated T cells; (6) MNC from synovial fluids, but not bone marrows, exhibited spontaneous Ig production in excess of stimulated synovial fluid cellular or peripheral blood Ig elaboration. These observations indicate selective impairment of peripheral blood MNC IgG and, particularly, IgM secretion in RA. This defect appears to reflect accessory cell influences which differ from normal as well as the sequestration of primed or activated cells in the synovial fluid. | |
| 7360040 | Pyoderma gangrenosum: clinical and laboratory findings in 15 patients with special referen | 1980 Mar | Fifteen consecutive patients with PG have been studied during the period 1971-78. Systemic disease was found in 13 of the patients and preceded the skin disease in 10 patients by 1-25 years. Only two patients had ulcerative colitis. One patient had paroxysmal nocturnal hemoglobinuria and three patients had an IgA myeloma. Eight patients had polyarthritis; this was classical seropositive rheumatoid arthritis in two patients, and a seronegative inflammatory polyarthritis in six patients. Four patients had an unusual progressive erosive seronegative polyarthritis without evidence of granulomatous bowel disease, psoriasis, genital, urinary tract or eye disease. In three of these four patients the arthritis preceded the PG. Synovial fluid analysis showed depressed complement levels and in one patient deposits of immunoglobulins and complement were demonstrated in the synovial membrane. The course of the arthritis was progressive with development of disabling joint deformities and erosive destruction of joints, despite treatment with penicillamine, corticosteroids and nonsteroidal anti-inflammatory drugs. One other patient had severe degenerative joint disease and chondrocalcinosis in association with a seronegative inflammatory polyarthritis, and another patient had ulcerative proctitis and severe degenerative joint disease secondary to chronic seronegative inflammatory polyarthritis. None of the patients had colitic arthritis, but in view of the association between PG and ulcerative colitis, some patients previously reported with PG and joint disease may have been suffering from the arthritis of ulcerative colitis. PG developed at the site of skin trauma in six patients. The natural history of the skin disease ran one of two courses: an acute, progressive course in which the ulcers rapidly enlarged until arrested by treatment; and a chronic course in which the lesions extended slowly and which after a period of weeks began to show signs of spontaneous healing. In only the patients with ulcerative colitis was there any correlation between the activity of the associated disease and the onset and progression of the skin disease. Serum complement levels were normal and no circulating cryoprecipitable immune complexes were found. Skin histology showed no evidence of vasculitis and direct immunofluorescence examination of involved skin was negative for IgG, IgM, IgA and C3. No consistent abnormality of cell-mediated immunity or neutrophil function was found and no significantly increased prevalence of any HLA antigen type was noted. Twelve patients have been treated with systemic corticosteroids. Six of these patients developed serious steroid complications and four patients have died, all from complications of steroid therapy. |