Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 1902874 | Regulation of plasminogen activator activity in arthritic joints. | 1991 Feb | The plasminogen activator (PA)/plasmin system has been implicated in the inflammation and connective tissue remodelling occurring in arthritic joints. PA activity is detected in cultures of human monocytes, synoviocytes and chondrocytes and can be regulated by a variety of cytokines found in diseased joints; PA inhibitors (PAI-1 and/or PAI-2) are also produced by these cells. We have shown that human monocytes can synthesize both urokinase-type PA (u-PA) and tissue-type PA (t-PA). One cytokine present in rheumatoid synovial fluids, granulocyte macrophage colony stimulating factor (GM-CSF), stimulates monocyte u-PA production; since this cytokine can also be produced by activated monocytes and other cell types in joints, than a "CSF network" can be produced leading to u-PA production. Another monocyte cytokine, interleukin 1, causes human synoviocytes to increase their u-PA expression, a response which can be dependent on the presence of endogenous cyclooxygenase products; this cytokine also causes human chondrocytes and cartilage tissue to produce increased u-PA and t-PA activity, i.e., under conditions during which cartilage is resorbed. | |
| 2130212 | [Coexistence of myelofibrosis and collagen diseases]. | 1990 | Hematologic abnormalities are common in association with collagen diseases, specially Systemic Lupus Erythematosus and include anemia, neutropenia, thrombocytopenia with alterations in lymphocyte subpopulations. On the other hand, patients with unexplained fibrosis of the bone marrow (the syndrome of idiopathic myelofibrosis or primary myelofibrosis) have clinical and laboratory evidence of immunologic dysfunction. Clinical findings include the presence of arthritis, vasculitis and erythema nodosum. Laboratory abnormalities include the presence of circulating immune complexes, antinuclear antibodies, positive direct Coombs test, elevated latex fixation and a circulating lupus type anticoagulant. Total hemolytic complement markedly depressed has also been reported. These data suggest that immunologic mechanisms associated with activation of the complement system play an important role in the disease process of some patients with agnogenic myeloid metaplasia with myelofibrosis. A review of the literature revealed that myelofibrosis occurring in the setting of collagen diseases is rare. However, a role for immunologic factors in the pathogenesis of myelofibrosis is also supported by the patients with coincident well defined collagen disease and myelofibrosis. In this report, we present two patients with such an association. Case 1 was a 58-year-old male with a two year duration history of rheumatic arthritis. He had bone erosions on hands, splenomegaly and myelofibrosis. Rheumatoid factor (latex) was positive: 1:2560. He had positive LE cells and hypocomplementemia: 37 CH50/ml (NV 70-150). The patient did not meet criteria for SLE. Case 2 was a 36-year-old female admitted because of dyspnea and fever. Diagnosis of myeloid metaplasia with myelofibrosis and progressive systemic sclerosis had been made four years before hand.(ABSTRACT TRUNCATED AT 250 WORDS) | |
| 2399373 | [Pyoderma gangrenosum and paraneoplastic chronic polyarthritis disclosing Hodgkin's lympho | 1990 Mar | Pyoderma gangrenosum is a rare skin disease of unknown pathogenesis associated, in almost 8 out of 10 cases, with a systemic disease, notably enterocolitis or hemopathy. We report the case of a 57-year old man who had been presenting with pyoderma gangrenosum for 5 years when he developed a rheumatoid-like seronegative chronic polyarthritis. The occurrence, some time later, of a supraclavicular adenopathy led to the diagnosis of Hodgkin's disease. To our knowledge, the pyoderma-chronic polyarthritis-Hodgkin's lymphoma association has never been reported. Treatment of the lymphoma resulted in complete disappearance of cutaneous and articular symptoms. The fact that neither the skin disease nor the polyarthritis recurred during a 3-year follow-up after treatment was discontinued, incites us to discuss the possibility that the pyoderma and the polyarthritis observed in this patient were neoplastic diseases. | |
| 2608570 | Lymphoplasmacytoid lymphoma elaborating lambda chain paraprotein with amyloid deposition i | 1989 May | A woman presented with painful enlargement of her parotid and submandibular glands. She was shown to have the previously unreported combination of idiopathic thrombocytopenic purpura, Sjögren's syndrome, Hashimoto's disease, and myasthenia gravis. Parotid gland biopsy and bone marrow examination showed the presence of a rare lymphoplasmacytoid lymphoma. There was amyloid deposition in the parotid glands, gums and on muscle biopsy. Immunohistochemical staining of the parotid lymphoma and amyloid was monotypic for lambda light chains, and there was also a lambda chain paraprotein. It is felt that the lymphoplasmacytic lymphoma was responsible for the light chain amyloidosis. | |
| 3409548 | Impaired release of natural killer cytotoxic factor in patients with primary Sjögren's sy | 1988 May | The impaired natural killer (NK) cell activity against K562 target cells of patients with primary Sjögren's syndrome (primary SS) was re-examined in a 2-year follow-up study of 10 patients and 10 normal controls. The ability of blood mononuclear cells (BMNC) to form effector/target cell conjugates and to release NK cytotoxic factor (NKCF) were studied. NK cell activity of the patients was unchanged low (P less than 0.01) compared with the controls. The number of effector/target cell conjugates did not differ between patients and controls, whereas NKCF-release from interferon-stimulated BMNC was significantly (P less than 0.01) reduced in the patients with primary SS and positively correlated to the reduced NK cell activity (r = 0.85, P = 0.0002). The permanently low NK cell activity of patients with primary SS appears therefore, at least in part, to be due to an impaired release of NKCF and not to a defective ability of effector cells to recognize and/or adhere to target cells. | |
| 3202533 | [Heterogeneity of large granular lymphocyte leukemia. 2 cases]. | 1988 | Large cell granulocytic leukemia (LCGL) or proliferative lymphocyte T gamma disease, characterized cytologically by the presence of lymphocytes with intracytoplasmic azurophil granules, raises the problem of whether or not it is monoclonal in character. However, although it may resemble a chronic lymphoid T leukemia or Felty's syndrome, it differs by the constant finding of infiltration of the splenic red pulp by large granular lymphocytes. Studies of their immunologic phenotype and functional activity produce heterogeneous results. The disease course varies considerably: the serious nature of the infections, knowledge of the physiopathologic mechanism of the neutropenia and the importance of the tumoral syndrome could represent therapeutic indications the modalities of which have still to be defined. | |
| 3091718 | A double-blind crossover trial of CMC- and mucin-containing saliva substitutes. | 1986 Aug | The aim of this investigation was to describe and to compare the effectiveness of a CMC- and a mucin-containing saliva substitute. 22 post-radiation patients, 17 Sjögren's Syndrome patients and 3 patients with xerostomia of unknown origin used a CMC- and a mucin-containing saliva substitute, each for 1 week in an arbitrary sequence. Neither the patient, the assistant, nor the physician were aware of the substitute being used. Each patient had to complete a questionnaire at 3 different intervals during the trial. One of the conclusions of this study is that mucin-containing substitutes are preferred by patients when compared to CMC-containing substitutes. | |
| 1888202 | Interleukin 2 production in a family with systemic lupus erythematosus and a C4Q0 heterozy | 1991 Aug | Interleukin 2 production was studied in a family with systemic lupus erythematosus (SLE) and a C4Q0 heterozygous inheritance. Autoimmune manifestations seemed to be associated with the HLA haplotype containing the C4Q0 allele, which was shared by all four ill family members. Concentrations of interleukin 2, however, did not associate either with the haplotype or with the clinical or serological manifestations, as diminished concentrations of interleukin 2 were found in only two subjects with SLE. Thus the defect in this family seemed to be acquired rather than genetically conditioned. | |
| 2706027 | Genetic studies of Ro (SS-A) and La (SS-B) autoantibodies in families with systemic lupus | 1989 Apr | Using enzyme-linked immunosorbent assays, autoantibodies to Ro (SS-A) were detected in the sera of 21% of the first-degree relatives and 11% of the second-degree relatives of anti-Ro-positive probands with systemic lupus erythematosus (SLE) or primary Sjögren's syndrome, as compared with 3% of normal control subjects (P = 0.003 and P = 0.09, respectively). In a parallel study, anti-Ro occurred in 28% of the first-degree relatives of unselected members of families of SLE patients, regardless of the proband's serologic status, compared with 6% of the relatives from normal healthy families. Antibodies to La and to Sm/nuclear RNP were infrequent. Anti-Ro occurred in 41% of the relatives considered to have a dominant, non-HLA-linked "autoimmune trait" by virtue of having any autoimmune disorder and/or serologic abnormality (antinuclear antibodies, anti-single-stranded DNA, or biologic false-positive VDRL test result), as compared with only 2% of the healthy, seronegative relatives without the trait (P = 0.009). Moreover, HLA-DR2 and/or DR3 occurred in 90% of anti-Ro-positive subjects, regardless of their clinical status. These results demonstrate that the Ro autoantibody response occurs frequently in relatives of patients with SLE and is genetically mediated by both major histocompatibility complex and non-major histocompatibility complex effects. | |
| 3760565 | IgG subclasses of anti-tetanus toxoid antibodies in adult and newborn normal subjects and | 1986 Oct 15 | The IgG subclasses of anti-tetanus toxoid (anti-TT) antibodies were quantitated in normal sera and sera from patients with rheumatic disease. Detection relied on a set of four mouse monoclonal antibodies, each of which showed specificity for the respective isotype, independent of gamma-chain allotype or light chain class of the human antibody. Approximately 90% of the total anti-TT activity in normal adults and patients with Sjogren's syndrome was IgG1. In addition, IgG4 antibodies were detected in one-half the samples, but IgG2 and IgG3 antibodies were observed in only two out of 36 sera. However, antibodies elicited in children immunized with TT were exclusively IgG1 and IgG3, with IgG4 antibodies detectable only at birth (presumably due to transplacental passage of antibody) in three of 12 children. In contrast to normal adults, patients with systemic lupus erythematosus (SLE) and drug-induced autoimmunity (DIA) had a more promiscuous isotype profile. IgG2 and/or IgG3 anti-TT antibodies were detected in 13 of 22 SLE patients and IgG3 antibodies in six of 11 patients with DIA. IgG4 anti-TT antibodies were predominant in seven of these 33 patients. These findings suggest that IgG isotypes may depend on the frequency of the stimulus, but global alterations in immunologic status as reflected in systemic autoimmune disease may override the homeostatic mechanisms that control isotype restriction. | |
| 3487660 | A case of Sjögren's syndrome with valvular diseases. | 1986 Jan | The case of a 61 year old woman with Sjögren's syndrome with aortic and mitral stenosis is reported. She suffered from rheumatic fever at a young age. Physical and echocardiographic examinations showed findings of mitral and aortic valve stenosis. In addition, she had experienced xerostomia, a gritty sensation in the eyes and Raynaud's phenomenon. Blood examination showed hypergammaglobulinemia, positive rheumatoid factor, antinuclear and anti-Ro (SS-A) antibodies. The diagnosis of Sjögren's syndrome was confirmed by sialography and biopsy of the labial salivary gland. The combination of valvular disease and Sjögren's syndrome is rare and the etiological correlation is discussed. | |
| 3109022 | Characterization of a crossreactive idiotype in Sjögren's syndrome. | 1986 | Sjögren's syndrome (SS) is characterized by lymphoid infiltration of the salivary glands and autoantibody production. Rheumatoid factor (RF) in patients with primary SS (1 degree SS) contains a crossreactive idiotype (CRI) defined by a monoclonal antibody (MoAb 17-109). This CRI was located on the kappa light chain by immunoblotting methods. A high frequency of CRI+ B cells was found in SS salivary gland biopsies, suggesting this tissue as the site of production for this autoantibody. Further characterization of CRI+ RF from SS patients was performed using antibodies prepared against synthetic peptides corresponding to the hypervariable region of RF paraproteins from patients with Waldenström's macroglobulinemia (WM). These results demonstrate a close structural relationship between RF in SS and WM patients. To analyze the genes that encode these RF in SS patients, B cell hybridomas that secreted CRI+ immunoglobulin were created and their DNA analyzed by Southern blot techniques. These hybridomas will allow us to determine the DNA sequence of kappa genes encoding the CRI and to identify adjacent regulatory genes that may promote high levels of CRI expression. | |
| 3075461 | CD5-expressing B lymphocytes in the blood and salivary glands of patients with primary Sjà | 1988 Apr | CD5, the human counterpart of Ly-1 molecules in the mouse, are detectable but weakly expressed on a minute fraction of circulating B cells. The number of CD5 + B cells in the blood of patients with Sjögren's syndrome was slightly higher than in control blood, but it became statistically significant after treatment of the cells with phorbol myristic acetate. These numbers were even higher in patients with homogeneous serum bands than in the others. A few scattered cells were stained with anti-human IgM antibody on salivary gland sections, and among them 5-10% were found to be positive for anti-CD5. | |
| 3293255 | [Comparative evaluation of the treatment of Sjögren's syndrome with anti-rheumatic prepar | 1988 | The paper is devoted to comparative assessment of combined therapy of prednisolone, chlorambucil, chloroquine phosphate and ibuprofen at small doses and its effect on clinicolaboratory signs of Sjogren's disease in 80 patients in the course of 1 and 5 years. Patients of the control group received only local therapy of the parotid glands. The results have demonstrated that combined therapy at small doses of prednisolone and chlorambucil (5 mg + 4 mg) is an effective method of treatment of the stomatological, ophthalmological and articular manifestations of SD and is also capable of preventing the systemic signs of disease. Combined therapy with chloroquine phosphate and ibuprofen neither influenced the clinicolaboratory signs of disease nor prevented disease progression with the development of systemic signs of diseases of various degrees. Disease progression was observed in 80% of patients receiving no basic drugs or receiving chloroquine phosphate+ibuprofen while in groups of patients receiving small doses of prednisolone and chloambucil disease progression was observed in 20% only. | |
| 3489027 | Key questions in a dry eye history. | 1986 Jul | The literature has been reviewed to derive a dry eye history questionnaire. The questions included examine for primary and secondary symptoms as well as assess for increased risk associated with age, sex, contact lens wear, medication use, and systemic and ocular factors that may be associated with dry eye syndromes. At the risk of obtaining responses of reduced validity, the questionnaire, administered by an assistant, may be preferred to direct interrogation for routine screening. Apart from serving as an indication of the presence of a dry eye condition, the questionnaire results may successfully identify individuals who are at risk for developing dry eye problems at a later time, especially those individuals exposed to provocative factors such as contact lens wear. A screening based on questionnaire results will help identify patients requiring further examination for dry eye conditions and associated differential diagnosis. | |
| 2869184 | A case of Sjögren's syndrome with severe anemia due to myelitis. | 1986 Jan 15 | An unusual case of Sjögren's syndrome presenting with severe anemia as the predominant clinical feature is described. Histological examination of a bone marrow biopsy specimen demonstrated that the patient's anemia was caused by myelitis and vasculitis of the small intraosseous vessels. Our report might stimulate a more thorough investigation of bone marrow in patients with connective tissue diseases and anemia. | |
| 2448073 | Selective impairment of alpha-interferon-mediated natural killer augmentation in Sjögren' | 1987 Nov | Natural killer (NK) function has been shown to be impaired in several autoimmune diseases including Sjögren's syndrome (SS). In the present study, in vitro effects of alpha-interferon (alpha-IFN), gamma-IFN and interleukin 2 (IL-2) on the NK cell activity were examined to analyse the regulatory system of NK-augmentation in patients with SS. The responsiveness of NK cell activity to alpha-IFN was markedly depressed in SS patients compared with normal controls, whereas the responsiveness to gamma-IFN was within normal limits. This is the first demonstration of the selective hyporesponsiveness of NK cell activity to one type of IFN in a certain disease. In addition, the kinetics study of NK-augmentation in normal donors revealed that alpha-IFN enhanced NK cell activity with a faster profile than gamma-IFN. These findings imply substantial differences between the two types of IFN in their mechanisms for enhancing NK cell activity, which deserve attention in evaluating the effects of IFNs. The present study also demonstrated that IL-2 could induce significantly higher levels of NK cell activity than alpha-IFN or gamma-IFN in SS and that this enhancing effect was almost comparable to that in normal controls. Thus, there seem to be multiple regulatory mechanisms for enhancement of NK cell activity, and a portion of the mechanisms may be selectively impaired in certain human diseases such as SS. The selective hyporesponsiveness to alpha-IFN could be relevant to the idea of viral participation in pathogenesis of SS. | |
| 3293257 | [Effectiveness and safety of using cyclosporin A in the treatment of primary Sjögren's sy | 1988 | We used oral cyclosporine-A (CyA) (5 mg/kg/day) initially in a double blind study for 6 mos. 10 patients received CyA and 10 placebo. At the end of this study it was observed that CyA improved subjective xerostomia, while subjective xerophthalmia, parotid gland enlargement, Schirmer-I-test and parotid flow rate did not show any significant differences in the two study groups. 9 of 10 patients who had received CyA for 6 mos and 9 of 10 in the placebo group continued in an open trial (CyA at the same dose) for an additional 6 mos. At the end of the study the only efficacy of CyA observed was improvement of subjective xerostomia. The side-effects observed were hypertrichosis (14 persons), mild hypertension (4), infections (5) and 3 dropped out because of nausea, tremor, paresthesias and infections. In conclusion, small doses of CyA for 12 mos are rather ineffective for Sjogren's syndrome. | |
| 1779927 | Oxidative stress responses in Escherichia coli and Salmonella typhimurium. | 1991 Dec | Oxidative stress is strongly implicated in a number of diseases, such as rheumatoid arthritis, inflammatory bowel disorders, and atherosclerosis, and its emerging as one of the most important causative agents of mutagenesis, tumorigenesis, and aging. Recent progress on the genetics and molecular biology of the cellular responses to oxidative stress, primarily in Escherichia coli and Salmonella typhimurium, is summarized. Bacteria respond to oxidative stress by invoking two distinct stress responses, the peroxide stimulon and the superoxide stimulon, depending on whether the stress is mediated by peroxides or the superoxide anion. The two stimulons each contain a set of more than 30 genes. The expression of a subset of genes in each stimulon is under the control of a positive regulatory element; these genes constitute the OxyR and SoxRS regulons. The schemes of regulation of the two regulons by their respective regulators are reviewed in detail, and the overlaps of these regulons with other stress responses such as the heat shock and SOS responses are discussed. The products of Oxy-R- and SoxRS-regulated genes, such as catalases and superoxide dismutases, are involved in the prevention of oxidative damage, whereas others, such as endonuclease IV, play a role in the repair of oxidative damage. The potential roles of these and other gene products in the defense against oxidative damage in DNA, proteins, and membranes are discussed in detail. A brief discussion of the similarities and differences between oxidative stress responses in bacteria and eukaryotic organisms concludes this review. | |
| 1647754 | Effect of auranofin on cytokine induced secretion of granule proteins from adherent human | 1991 Jun | The effect of auranofin on granule protein secretion from neutrophils was investigated by a haemolytic plaque assay which can detect release of lactoferrin and myeloperoxidase from single adherent neutrophils. Lactoferrin secretion in response to N-formyl-methionyl-leucyl-phenylalanine (fMLP) was enhanced at low (0.25-1.0 micrograms/ml) and inhibited at high concentrations of auranofin (50% inhibition (IC50) at 3.7 micrograms/ml). A similar biphasic effect was also seen on degranulation mediated by granulocyte-macrophage colony stimulating factor (GM-CSF) (IC50 1.8 micrograms/ml). In contrast, exocytosis mediated by tumour necrosis factor was inhibited even at low concentrations of auranofin (IC50 0.6 micrograms/ml). Secretion induced by phorbol 12-myristate 13-acetate and A23187 was only inhibited at very high auranofin concentrations (IC50 10 and 8 micrograms/ml respectively). The effect of auranofin on myeloperoxidase secretion was also assessed and the IC50 values for the respective agents were as follows: tumour necrosis factor 0.7 micrograms/ml, fMLP 1.6 micrograms/ml, and phorbol myristate acetate 7.6 micrograms/ml. When neutrophils were preincubated with auranofin (4 micrograms/ml) and then exposed to fMLP, tumour necrosis factor, or GM-CSF in the absence of auranofin, lactoferrin release was enhanced if the preincubation time was short (one to three minutes) and inhibited when the time of preincubation was longer. It was concluded that auranofin, at concentrations achieved in the serum of patients, is a potent inhibitor of cytokine induced release of granule proteins from adherent neutrophils. This finding may be of clinical importance and shed light on the mechanism by which auranofin acts in rheumatoid arthritis. |