Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
2972059 Pharmacological criteria for risk-benefit evaluation of NSAIDs. 1988 Evaluation of new non-steroidal anti-inflammatory drugs (NSAIDs) must compare efficacy and toxicity with existing compounds. Real progress involves maintaining effectiveness while decreasing toxicity. It is relatively easy to assess the effects of NSAIDs in animal models, and to determine gastrointestinal toxicity. However, although the ratio of active and toxic doses in animals can be extrapolated to man, the approach is limited and the NSAID needs to be assessed in a clinical setting as early as possible. In France, a national survey system has reported a wide range of adverse effects related to NSAIDs and shown important differences between compounds. Overdosage may be one of the factors responsible for toxicity, therefore pharmacokinetic evaluation is useful. In some disease states e.g. rheumatoid arthritis, there is a higher possibility of saturation pharmacokinetics with some drugs. Other pharmacokinetic parameters of interest are half-life, functions limiting activity, and hepatotoxicity. Furthermore, different pharmacokinetic parameters are required for different forms of disease. In acute states, the NSAID should have a short half-life and low protein binding and vice versa in chronic states. An important goal is to develop more selective NSAIDs regarding mechanisms of action or distribution into diseased tissues.
3040797 Normal suppressive T cell function of Epstein-Barr virus-induced B cell activation in Grav 1987 Sep Several studies have demonstrated abnormalities of T cell regulation of Epstein-Barr virus (EBV)-induced B cell activation in systemic autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis. To investigate whether this abnormality is a common feature of other autoimmune diseases, we studied 10 EBV-immune normal subjects and 22 EBV-immune patients with Graves' disease (GD); 11 had newly diagnosed hyperthyroidism, and 11 had received carbimazole treatment for hyperthyroidism for at least 6 months. Peripheral B lymphocytes infected with EBV were cultured for 20 days in the presence or absence of autologous T cells at different ratios. Immunoglobulins M and G secretion into the supernatants was 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 normal subjects and newly diagnosed GD patients (0.65 vs. 0.63 on the 16th day and 0.77 vs. 0.72 on the 20th day of culture, respectively). In carbimazole-treated patients, the appearance of functional suppressor T cells was delayed slightly, but the overall suppression ratios on the 16th and 20th days were normal. Thus, a T cell regulation abnormality of EBV-induced B cell activation could not be demonstrated in patients with untreated hyperthyroid GD, suggesting that the autoimmune reactivity in such patients is probably dependent upon a specific thyroid suppression defect rather than a generalized suppression defect.
2443837 Expression, detection and assay of a neoantigen (Neo-CRP) associated with a free, human C- 1987 May It has previously been reported that human C-reactive protein (CRP) can exist in at least two molecular conformations distinguished by antigenic, electrophoretic and ligand-binding reactivities. In the present study we describe the formation, detection and distinctiveness of a conformation expressing a CRP neoantigen (neo-CRP), and report that this form is characteristic in vitro of a free CRP subunit. Soluble native-CRP was found to express neo-CRP antigenicity upon treatment with acid; upon urea-chelation or heating in the absence of calcium; and upon adsorption onto uncoated polystyrene plates. Native-CRP bound by capture ELISA to phosphorylcholine-containing ligand or anti-native-CRP did not express neo-CRP antigenicity, suggesting that PC ligand- or antibody binding is not sufficient to induce expression of the neoantigen. Human CRP which expressed neo-CRP antigenicity had limited solubility and tended to aggregate in buffers of ionic strength 0.15, but remained soluble when the ionic strength was reduced to 0.015. Soluble urea-chelated or acid-treated CRP molecules expressing neo-CRP antigenicity chromatographed and electrophoresed as a single protein with a Mr of approx. 22,000, indicating that the CRP neoantigen can be expressed on free CRP subunits and this expression need not require proteolysis. Further, molecules expressing neo-CRP antigenicity were detected in the plasma of patients with rheumatoid arthritis. The identification and characterization of this CRP neoantigen should serve as a useful marker in studies of CRP subunits and biologically relevant forms of CRP, and should contribute to the elucidation of the role of CRP in the acute inflammatory response.
2011712 Platelet-associated immunoglobulins in patients with primary Sjögren's syndrome. 1991 Ten patients with primary Sjögren's syndrome (7 females) were examined in order to evaluate whether in vivo-bound platelet-associated immunoglobulins (PAIg) and/or in vitro binding of circulating Ig to normal platelets influences platelet function. With an ELISA technique it was found that 9/10 patients had increased amounts of in vivo PAIgG, 4/10 patients of in vivo PAIgA and 5/10 patients of in vivo PAIgM. There was no correlation between patients platelet aggregability and the presence of in vivo PAIg. Incubation of platelets from a healthy person with plasma from the 10 patients caused in vitro binding of IgG in 7/10 cases, of IgA in 0/10 cases and of IgM in 1/10 cases. Adenosine diphosphate (ADP)-induced aggregability of the normal platelets was impaired in 7/10 incubation experiments (no correlation to in vitro PAIg) and unchanged in 3/10 cases. Epinephrine- and collagen-induced platelet aggregability was unchanged in all cases. It is concluded that increased amounts of in vivo and in vitro PAIg seem to occur frequently in patients with primary Sjögren's syndrome, but do not influence platelet aggregability.
2184194 Macro enzymes: prevalence, composition, detection and clinical relevance. 1990 Feb The presence of a macro enzyme, i.e. an enzyme with an abnormally high molecular weight, frequently leads to a genuinely increased serum activity or an interference in laboratory assays. This may thereby result in false positive diagnoses, such as acute myocardial infarction or pancreatitis. The various forms of macro enzymes are reviewed. In the case of immune complexes the immunoglobulins and (iso)-enzymes involved are discussed, as well as the specificity of the interaction, the prevalence and clinical relevance, associations with autoimmune or other diseases, and their behaviour in laboratory assays.
2707178 Endobronchial pseudolymphoma associated with Sjögren's syndrome. Report of a case. 1989 Mar A case of pseudolymphoma occurring in a patient with Sjögren's syndrome is described. The lesion, which gave rise to intraluminal tumor masses in the airway, grew progressively, resulting in severe dyspnea. Treatment with prednisolone brought relief. The lymphoproliferative disorders, the principle clinical manifestation of which was pseudolymphoma, might have given rise to the M-component of the IgA-Ktype.
1787500 Peripheral T cell lymphoma with Sjögren's syndrome: a report with immunologic and genotyp 1991 Nov We describe an unusual case of peripheral T cell lymphoma, occurring 4 years after the diagnosis of primary Sjögren's syndrome. Immunologic and genotypic studies demonstrated the T cell origin of this lymphoma.
1666416 Peripheral neuropathy associated with Sjögren's syndrome: pathologic and immunologic stud 1991 Sep Two cases of Sjögren's syndrome accompanied by peripheral neuropathy are reported. The level of anti-endothelial cell antibody was increased in both patients. Immunofluorescent deposits of immunoglobulin and C3 component were detected in the vasa nervorum of both cases. The pathological findings showed damage to the endothelial cells in the same vessels. The findings suggest that injury from immune complex and anti-endothelial cell antibody may be the immunological factor in the induction of peripheral neuropathy.
2060162 Serial measurements of anticardiolipin antibodies in primary Sjögren's syndrome. 1991 Mar Twenty-four out of 54 patients with primary Sjögren's syndrome (SS) were shown to be positive for IgG and/or IgM anticardiolipin antibodies (aCL). Extraglandular manifestations were related to the IgG-, but not to the IgM-aCL. Twenty SS patients were examined over a 3 year period. Of these, 6 displayed a marked increase in IgG- and IgM-aCL and, among them, 4 developed extraglandular manifestations of SS throughout the follow-up.
2013357 Systemic lupus erythematosus exacerbated by piroxicam. 1991 A patient with Sjögren's syndrome and seronegative polyarthritis is reported. After piroxicam intake and sun exposure she developed subacute cutaneous lupus erythematosus lesions with Ro antibodies. Despite drug withdrawal, typical cutaneous lesions and serological markers of systemic lupus erythematosus (SLE) progressively appeared. The use of piroxicam and other nonsteroidal anti-inflammatory drugs with photosensitizing potential in patients with Sjögren's syndrome, sicca syndrome or a high suspicion of a collagen disorder should be avoided because these drugs may trigger a latent SLE.
3367095 A 52-kD protein is a novel component of the SS-A/Ro antigenic particle. 1988 May 1 Anti-SS-A/Ro autoantibodies are found in the sera of patients with Sjogren's syndrome (SS) and SLE. In the course of analyzing 61 SS patients for their autoantibody profiles, we found that 42 were positive for anti-SS-A by double diffusion in agarose and demonstrated precipitin lines identical to that produced by a prototype anti-SS-A serum. Further analysis of these SS-A antibody-positive sera by Western blotting of cell extracts revealed that 21 sera reacted with two proteins of 60 and 52 kD, 13 sera reacted with 52-kD protein, two detected only 60 kD, while six were nonreactive. Affinity-purified anti-60-kD and anti-52-kD antibodies reacted exclusively with their corresponding antigens. Partial proteolysis of these proteins did not reveal common degradation fragments. Thus the 52- and 60-kD proteins were found to be antigenically and apparently structurally distinct from each other. They were also distinct from 48-kD SS-B/La protein. In immunoprecipitation using labeled cell extracts, affinity-purified anti-52-kD antibodies brought down the 52-kD protein as well as the 60-kD band. In [32P]orthophosphate-labeled HeLa cell extract both antibodies precipitated the same spectrum of small RNAs (hYl-5). In indirect immunofluorescence, anti-52-kD and anti-60-kD antibodies immunolocalized in similar subcellular structures and showed similar punctate nuclear staining patterns. Western blot analysis revealed that both proteins were present in lymphocytic as well as epithelial human cell lines tested. The data above define a new antigen of 52 kD which is another component of the SS-A particle and is associated in complex formation with the previously reported 60-kD protein.
3125274 Sicca symptom in a patient with hemochromatosis: minor salivary gland biopsy for different 1987 Dec This paper reports a case of hemochromatosis with sicca symptom. The patient was a 59-year-old female who had been received a series of intravenous iron injections and blood transfusions because of anemia owing to side-effects of a chemotherapeutic agent. She complained of dry mouth and dry eyes in addition to symptoms of hemochromatosis. The histological appearance of the labial salivary gland, with heavy deposition of iron in acinar and duct epithelial cells and absence of focal lymphoid cell infiltration, did not support a diagnosis of Sjögren's syndrome but suggested functional damage of the salivary glands related to iron. The patient was given desferrioxamine, and clinical symptoms improved; re-examined labial salivary gland biopsy showed no iron deposition in any parenchymal cells after the treatment.
3816098 Neonatal lupus erythematosus with congenital heart block associated with maternal systemic 1986 Dec We report the presence of complete heart block in a girl whose mother has anti-Ro antibodies and is suffering from systemic lupus erythematosus with Sjögren's syndrome. HLA antigens studies in the two patients support the hypothesis described recently that HLA DR3 is responsible for the production of anti-Ro antibodies and not for the phenotypic expression of the tissue injury.
1720300 T cell receptor expression in Sjögren's syndrome. 1991 Oct T lymphocytes expressing the gamma/delta T cell receptor and B lymphocytes expressing CD5 are known to occur in expanded numbers in the peripheral blood of patients with primary Sjögren's syndrome. The cellular infiltrates for the surface phenotypic markers for alpha/beta and gamma/delta T cell receptors, CD4, CD8, CD45, and CD5 were examined in lip biopsy specimens from two patients with primary Sjögren's syndrome, six with secondary Sjögren's syndrome, and seven healthy controls. Most of the Sjögren's lip biopsy cellular infiltrates were T lymphocytes of the CD4 subset expressing the alpha/beta T cell receptor (mean 70%). The low prevalence of gamma/delta T cell receptor bearing cells in lip biopsy specimens is maintained in Sjögren's syndrome (mean 1.5%), and thus it seems unlikely that these lymphocytes bearing the gamma/delta T cell receptor have a major role in the immunopathology of Sjögren's syndrome. Over 70% of cells within the lesional infiltrate of primary and secondary Sjögren's syndrome expressed the CD5 and CD45 cell surface molecules.
2742642 [The significance and limits of cytologic diagnosis in myoepithelial sialadenitis]. 1989 Apr In case of myoepithelial sialadenitis cytological diagnosis by fine-needle aspiration biopsy is not a reliable measure, because the typical islets of myoepithelial cells can be demonstrated by cytology in only 6% of cases. Since lymphocytic infiltrations dominate the histological aspect a cytological specimen that contains these cell elements, may be taken as an indication for the presence of myoepithelial sialadenitis if a sicca syndrome exists at the same time. If a non-Hodgkin lymphoma has to be suspected after cytology, this must be followed by a histological verification (despite the fact that this suspicion was unfounded in all the cases mentioned here), because it is well known that in myoepithelial sialadenitis there is a danger of transformation into a malignant lymphoma. By detailed anamnestic data, especially by mentioning an existing sicca syndrome, the clinician can help the cytologist in assessing his findings properly.
3397971 A prospective study comparing incisional labial to incisional parotid biopsies in the dete 1988 Apr Simultaneous incisional biopsies of labial minor salivary glands and the superficial lobe of the parotid were accomplished in patients suspicious for sarcoidosis, Sjögren's disease, sialosis and lymphomatous changes in Sjögren's disease. Labial minor salivary gland biopsies identified sarcoidosis in 11 of 31 (36%) patients, compared to 29 of 31 (93%) patients using the parotid biopsy (p = 0.005). Similarly, the labial minor salivary gland biopsy confirmed 21 of 36 (58%) patients to have Sjögren's disease, compared to 36 of 36 (100%) (p = 0.005) patients confirmed using the parotid biopsy. Five patients with normal labial salivary gland biopsies were shown to have idiopathic hypertrophic sialosis with enlarged parotids identified by the parotid biopsy. Five additional patients were diagnosed with lymphoma occurring within the parotid glands of patients with Sjögren's disease, via the parotid biopsies, that were not identifiable with the labial minor salivary gland biopsy. The parotid biopsy consistently identified each disease entity in an earlier stage, and with more evident histopathology. Neither technique showed appreciable morbidity. Three of 77 patients showed a sensory loss related to labial salivary gland biopsy. No sensory or motor nerve loss was associated with the parotid biopsy.
3430506 Hereditary complement (C6) deficiency associated with systemic lupus erythematosus, Sjögr 1987 Oct Results of clinical, serologic and histologic studies documenting an association between hereditary C6 deficiency and a connective tissue disease are provided. The propositus had systemic lupus erythematosus with prominent discoid features, Sjögren's syndrome and hyperthyroidism. Serum C6 was undetectable by radial immunodiffusion and hemolytic assays. Serologic and typing studies performed on 9 family members suggested an autosomal codominant transmission. No correlation with a specific HLA phenotype was established.
3494156 [Complications following temporary occlusion of the nasolacrimal duct with tissue adhesive 1986 Dec This paper presents 4 cases in which the punctum had been temporarily occluded with tissue adhesive, still showing toxic tissue reaction years later. Abscess, dacryocystitis, dacryocystitis with dacryolithiasis, dacryocellulitis and polyposis were found. In the light of these findings and the relevant literature-especially with regard to late injuries-it is not advisable to use tissue adhesive, at least not for the purpose of punctal occlusion.
2546709 [Magnetic resonance tomography of the parotid gland: plain diagnosis and Gd-DTPA]. 1989 Jun Pathological lesions of the parotid gland were examined comparatively with different examination sequences both plain and with the contrast medium Gd-DTPA. There were 36 benign lesions (parotitis, Sjögren's syndrome, adenoma, etc.) and 24 malignant tumours (squamous cell carcinoma, adenocarcinoma, adenoid cystic carcinoma etc.) Examinations were carried out at 1.0 T with long and short spin echo sequences in transverse and frontal layer orientation before and after application of Gd-DTPA as contrast medium. In the patients suffering from parotitis the best results were obtained with plain T1 and T2 sequences; the contrast medium Gd-DTPA remained without superior diagnostic relevance. However, in Sjögren's syndrome (myoepithelial sialadenitis) administration of the contrast medium always yielded a characteristic honeycomblike pattern. In benign and malignant space-occupying growths MRI supplied additional diagnostic information with Gd-DTPA in respect of defining the tumour borderlines and paths of infiltration. MRI is now a significant diagnostic tool in inflammatory and tumorous lesions of the parotid gland.
2003013 Periductal lymphocytic infiltration of salivary glands in Sjögren's syndrome with relatio 1991 Feb We studied 113 patients who were suspected to have Sjögren's syndrome (SS) because they had dry mouth and dry eyes, and who were determined as not having any other autoimmune disease, to clarify the relationship of periductal lymphocytic infiltration of salivary glands to clinical and immunologic findings in relation to SS. Periductal lymphocytic infiltrations were observed in the labial and/or the parotid glands of 57 patients (P-group). The salivary glands of the other 56 patients did not demonstrate obvious histologic changes (N-group). The stimulated salivary flow rate of parotid glands of the patients in both the P- and N-groups was significantly reduced when compared with healthy persons. However, no difference in the flow rate was observed between the P- and N-groups. In contrast, the percentage of patients in the P-group with keratoconjunctivitis sicca was significantly higher than that of patients in the N-group. Percentage of gamma-globulin fraction and IgG level in the sera of the patients in the P-group were both significantly higher than those in the N-group. The percentages of patients who demonstrated the serum rheumatoid factor, anti-SS-A, and anti-SS-B antibodies were also significantly higher in the P-group than in the N-group.