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

ID PMID Title PublicationDate abstract
1865740 The lymphocyte transformation test with type II collagen as a diagnostic tool of autoimmun 1991 Aug Immunological disorders of the cellular type can be diagnosed by the lymphocyte transformation test (LTT). An autoimmune mechanism of certain cases of sensorineural hearing loss (SNHL) can be evaluated by using human inner ear tissue as an antigen. Recent studies have shown that type II collagen plays an important role, not only in some autoimmune mediated rheumatoid diseases, but also as an antigenic substrate of inner ear tissue in autoimmune sensorineural hearing loss. This paper deals with results of the lymphocyte transformation test using type II collagen as antigen in 68 patients with progressive sensorineural hearing loss (PSNHL) and 68 healthy volunteers. Thirty-four patients showed a strong stimulation in the lymphocyte transformation test, in contrast to only four volunteers in the control group, two of whom had a history of rheumatoid arthritis.
3150766 Quantification of circulating immune complexes by chicken anti-C4 micro ELISA. 1988 Sep A quantitative assay for C4-containing immune complexes (IC) by a solid phase anti-C4 micro ELISA is described. It is based upon the use of an affinity purified chicken anti-human C4 antibody to capture the immune complex, and protein A-alkaline phosphatase for detection. The chicken antibody was chosen as capture antibody because it does not react with rheumatoid factor, does not activate the human complement system and is not detected by anti-mammalian IgG antibodies or protein A. Increased levels of C4 containing circulating immune complexes (CIC) were detected in sera from patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and lung cancer, when compared with normal sera. Normal levels of C4 containing immune complexes were found in sera from patients with Bell's palsy.
3501972 A comparison of sleep in rheumatic and non-rheumatic patients. 1987 Oct The St. Mary's Hospital Sleep Questionnaire was used to investigate sleep in 439 hospitalized rheumatic and non-rheumatic patients. This questionnaire enabled an evaluation of both the level of sleep disturbance and the causes of such disturbance. The findings from this study indicated that there was little difference in the level of sleep disturbance between rheumatic and non-rheumatic patients. The sleep problem most frequently cited by rheumatic patients was pain. Noise appeared to be the worst environmental sleep problem in these patients. The only significant difference in the sleep problems reported by rheumatic and non-rheumatic patients, was that pain was cited more frequently in the rheumatic group. In order to determine whether sleep varied according to type of rheumatic disease, the rheumatic patients were divided into four diagnostic groups (rheumatoid arthritis; seronegative spondarthritis; osteoarthritis; other conditions). There were no significant differences between these groups in sleep disturbance or reported sleep problems.
2765012 Validity of the Center for Epidemiological Studies Depression Scale in arthritis populatio 1989 Aug Using data from 3 studies of patients with rheumatoid arthritis, we examined the extent to which responses to items in the Center for Epidemiological Studies Depression Scale (CES-D) are influenced by aspects of the disease process other than depression. Our findings suggested that 4 CES-D items (i.e., "I felt that everything I did was an effort," "I felt hopeful about the future," "My sleep was restless," and "I could not get going") may be influenced by aspects of the disease process and, thus, are not necessarily indicative of depression among persons with arthritis. The impact that these items have on the interpretation of CES-D scores was assessed in relation to 2 research issues: estimation of the prevalence and severity of depression in arthritis populations and identification of the determinants of depression among individuals with arthritis. Our results suggest that the original CES-D may overestimate the prevalence and severity of depression among patients with arthritis. The magnitude of this bias is modest, however. The results also suggest that in studies designed to identify the determinants of depression among individuals with arthritis, inclusion of the 4 items identified is unlikely to have any effect on study findings.
3482733 Juvenile chronic arthritis. 1987 Juvenile Chronic Arthritis is a relatively uncommon childhood disease. There are no absolute diagnostic tests and many classification criteria have evolved (4, 15, 7) based variably on joint number, disease course, associated clinical features and rheumatoid factor seropositivity. These are of no help diagnostically, but do allow investigative and follow-up studies to compare like with like. It is generally accepted that there are three main modes of onset, the commonest being pauci-articular with less than five joints in the first 3 to 6 months. Arising from the population immediately around the old MRC rheumatism unit at the Canadian Red Cross Memorial Hospital, Taplow, this accounted for 68%, with a poly-articular onset in 20% and systemic onset in 12%. Despite this low incidence of systemic illness, it remains a great challenge.
2737695 An association between Gc (vitamin D-binding protein) alleles and susceptibility to rheuma 1989 May Rheumatic fever is associated with exaggerated activity of B cells with massive production of antibody to the Group A streptococcus. Gc (vitamin D-binding protein) is constitutively expressed on B-cell membranes in association with membrane immunoglobulin, and could be involved in cell activation. We therefore looked for associations between the three major Gc alleles and susceptibility to rheumatic fever in a homogeneous Arab population. Patients with tuberculosis or rheumatoid arthritis and control donors, were studied in parallel. Allele frequencies in the controls, rheumatoid and tuberculosis patients were identical to those found in a previous study of normal Arab donors. However, there was a striking association between Gc2 and rheumatic fever. This allele was twice as common in these patients as in controls (p = 0.0024), and was present in 56.4% of all rheumatic fever patients.
2338013 Serum cholesterol and vitamins A and E in juvenile chronic arthritis. 1990 Mar Serum total cholesterol is decreased during acute infections and in adults with rheumatoid arthritis, probably partly because of enhanced lipid peroxidation. Oxidative stress also causes augmentation of inflammation and tissue damage in arthritic synovium. Therefore, concentrations of serum total cholesterol and the antioxidant vitamins A and E were studied in 125 children with juvenile chronic arthritis. Total serum cholesterol was significantly lower in the patients than in healthy children in most age groups and correlated with the markers of disease activity, haemoglobin and the erythrocyte sedimentation rate. In age- and sex-adjusted stepwise multiple linear regression, serum zinc had a significant predictive value for cholesterol. The vitamin A concentrations in the sera of the patients was virtually the same as in the healthy controls, though serum vitamin E concentrations were low (22.8 +/- 15.2 vs 30.5 +/- 4.3 mumol/l, p less than 0.001). The deficiency in vitamin E was not compensated for by another lipoperoxide antioxidant, glutathione peroxidase. Only serum cholesterol had an independent explanatory significance for vitamin E in multiple linear regression analysis (partial correlation 0.554, p less than 0.001). It is suggested that low vitamin E and impairment of the anti-oxidant protection further contribute to low serum cholesterol values in JCA.
2457140 Synovial fluid T cell reactivity against 65 kD heat shock protein of mycobacteria in early 1988 Aug 27 The in vitro proliferative response against a recombinant 65 kD Mycobacterium bovis protein that has 100% homology with the 65 kD protein of M tuberculosis was tested in synovial fluid and peripheral blood mononuclear cells from patients with rheumatoid arthritis (RA) and other types of chronic arthritis. An acetone precipitate (AP) of M tuberculosis, and a purified protein derivative (PPD) of M tuberculosis were also tested. Responsiveness of synovial fluid lymphocytes to the mycobacterial antigens was found both in patients with RA and in patients with other forms of chronic inflammatory arthritis, but not among controls. T cell reactivity against mycobacterial antigens was nearly always higher in synovial fluid than in peripheral blood in those patients who showed reactivity. A significant association was found between responsiveness of synovial T cells to the 65 kD protein and AP, but no relation between responsiveness to the 65 kD protein and PPD. Both the number of 65 kD protein responders and the mean proliferative response of synovial T cells to the 65 kD protein were inversely correlated with duration of joint inflammation. Thus, a 65 kD-protein-specific reactivity of synovial T cells, mainly present in an early stage of joint inflammation, may be responsible for triggering chronic arthritis.
2467352 Fc epitopes for human rheumatoid factors and the relationships of rheumatoid factors to th 1988 Work from our laboratories has shown that the major antigenic determinants for rheumatoid factors (RFs) are in the C gamma 2-C gamma 3 interface region of IgG in the same area that binds staphylococcal protein A (SPA). Furthermore, the Fc binding proteins of groups A, C and G streptococci as well as the Fc binding proteins induced on cell surfaces by herpes simplex virus type I also bind to the same area of IgG. These binding site similarities between RFs and the microbial Fc binding proteins suggested conformational similarities between the RF antigen combining regions and the Fc binding regions of the microbial proteins. This hypothesis was supported by the observation that antibodies to SPA bind to the antigen combining regions of most RFs as well as to the Fc binding region of the T15 group A streptococcal Fc binding protein. These findings indicate that RFs bear the conformational internal image of these microbial proteins and suggest that RFs could arise as antibodies to the idiotypic determinants on antibodies to microbial Fc binding proteins. Alternatively, microbial Fc binding proteins could present IgG to the immune system in a way that renders specific areas of the C gamma 2-C gamma 3 interface region immunogenic. These relationships between RFs and microbial Fc binding proteins may prove to be important for our understanding of the generation of RFs in rheumatoid arthritis.
3120583 Current modalities in arthritic diseases. 1987 Oct 30 Little progress has been made in identifying the etiologies of the major rheumatologic diseases, which substantially limits our ability to identify truly disease-modifying treatments. Despite this constraint, major advances in the suppression of the signs and symptoms of these diseases have been made. Second-line drugs such as methotrexate have gained wide acceptance among rheumatologists and may supplant gold as the major therapy for rapidly advancing rheumatoid arthritis. The nonsteroidal anti-inflammatory drugs (NSAIDs), however, remain the first line of treatment for arthritic conditions. In recent years, much has been learned about how the NSAIDs suppress the inflammation and pain of arthritis. Even here, however, several inconsistencies exist with our current understanding. New findings in neurobiology may shed light on some of these puzzling features. Although the number of NSAIDs currently available seems a bit overwhelming, rationale exists for their continued development. Many patients do not have a response to some or all of these agents, with noncompliance because of gastrointestinal intolerance being among the probable causes. New compounds that offer improved safety in this regard are greatly needed.
2646320 Cytokines in chronic inflammatory arthritis. II. Granulocyte-macrophage colony-stimulating 1989 Mar A liquid culture technique was used to study 23 synovial fluids (SF) (21 from inflammatory joint diseases and 2 noninflammatory SF) and supernatants of two cultured rheumatoid arthritis (RA) synovial tissues for colony-stimulating factor (CSF). The proliferative responses of human peripheral blood macrophage-depleted non-T cells treated with synovial fluids, supernatants of synovial tissue explants, and recombinant granulocyte-macrophage (rGM)-CSF were compared. Aggregates of cells that formed in long-term cultures (15 d) were similar for each applied agent and consisted of macrophages, eosinophils, and large blasts. Tritiated thymidine incorporation was proportional to the concentration of rGM-CSF and was accompanied by an increase in number and size of cellular aggregates formed in the cultures. CSF activity was observed in inflammatory SF, with tritiated thymidine uptake of 3,501 +/- 1,140 cpm in the presence of RA samples (n = 15) compared to 1,985 +/- 628 for non-RA inflammatory SF (n = 7) (P less than 0.05) and 583 +/- 525 for medium (n = 6) (P less than 0.01). The proliferative response to RA SF was often more apparent when the samples were diluted, because at higher concentrations the RA SF was inhibitory. Two RA SF were fractionated by Sephadex G100 column chromatography; low levels of CSF activity were detected in fractions corresponding to Mr of 70-100 kD, but the major CSF activity was found in the 20-24-kD fractions. A polyclonal rabbit anti-GM-CSF antibody eliminated the stimulating activity from both rGM-CSF and RA SF. Finally, a specific RIA identified significant levels of GM-CSF (40-140 U/ml) in the culture supernatants of 3 additional RA synovial tissues. These data document the local production of GM-CSF in rheumatoid synovitis and are the first description of this cytokine at a site of disease activity.
1887390 [The effect of drugs that correct regional blood circulation on the function of the paroti 1991 A study was made of the effect of some drugs that correct microcirculatory disorders (dimethylsulfoxide (DMSO), heparin, novocaine) on the function of the auricular salivary glands (ASG) in combined treatment of 20 patients suffering from Sjögren's disease (SD). It has been established that the use of the indicated remedies is conducive to a more rapid counteracting of the inflammatory process in the ASG, making it possible to stabilize their function for a long time in persons with the initial and marked stages of chronic parotitis (CP) but not preventing repeated exacerbations of CP. In order to maintain the therapeutic level of the response of the vascular bed of the ASG to DMSO, it is desirable that compresses with DMSO in a "pure" form be applied in 6 hours, using a 1% hydrocortisone ointment "laying" 1 to 2 times a day.
1978638 Molecular characterisation of C4 null alleles found in Felty's syndrome. 1990 Oct A higher prevalence of C4B null alleles is found in Felty's syndrome. The molecular basis of C4 null alleles was investigated by studying restriction fragment length polymorphisms (RFLPs) obtained with C4 and 21-hydroxylase (21-OH) DNA probes and by pulsed field gel electrophoresis in 30 subjects with Felty's syndrome. C4A null alleles were found in 10 subjects, and in five of these were associated with a deletion that included C4A and adjacent 21-OHA gene sequences. A 6.4 kilobase C4B-5'-specific Taq I fragment usually provided a reliable guide to the presence of a C4A deletion but unusually in one instance this fragment was found to be a marker of a functioning C4A gene. A C4B null allele was found in 17 subjects and was associated with a deletion involving C4B and 21-OHA gene sequences on only two occasions. There were no instances in which deletion of the 21-OHB gene occurred.
2287968 [A case of temporal arteritis associated with polymyalgia rheumatica and subclinical Sjög 1990 Aug A case of temporal arteritis (TA) associated with polymyalgia rheumatica (PMR) and subclinical Sjögren's syndrome (sub SjS) was presented in this paper. A 76 year-old-male was admitted with headache, fever and weight loss in April 1987. Myalgia of upper extremities and of thighs developed during the past two months before admission. He also had noticed bilateral wrist pain. Physical examination revealed slight cord-like thickening of left temporal artery with tenderness. Cerebral angiography disclosed narrowing of frontal and parietal branches of left temporal artery. Temporal artery biopsy was consistent with TA. Diagnosis of PMR was made by Bird's diagnostic criteria. Although sicca symptoms were not seen, sialography revealed moderate sialectasis. Pathological finding of salivary gland was compatible with sub SjS. Possibility of occult lymphoma was eliminated by CT scanning or myelogram. Laboratory evaluation disclosed slight anemia, leukocytosis and thrombocytosis. Blood chemistry showed no abnormal finding except for hyperfibrinogenemia. Serological studies indicated positive C-reactive protein and slight elevation of alpha 2 and beta globulin fractions of serum protein. Either rheumatoid factors, antinuclear antibodies, anti-smooth muscle antibodies, cryoglobulin or circulating immune complexes were not detected. The HLA-B8 and DR3, frequently detected in TA and SjS, were not identified. Tuberculin test was negative. These results suggested that immunological aberration not caused by genetic factors but by senescence would induce presence of TA associated with both PMR and sub SjS.
2477000 Epitope specificity of anti-La antibodies from patients with Sjögren's syndrome. 1989 Aug To investigate patterns of autoreactivity in Sjögren's syndrome, the epitope specificity of anti-La antibodies was determined using recombinant antigens bearing sequences of the amino, middle, and carboxyl portions of the La molecule. Sera from patients with primary as well as secondary Sjögren's syndrome reacted with all three fragments, although the magnitude of the responses varied markedly among individuals. Furthermore, the proportion of antibody binding directed to the different La epitopes showed considerable individual variations, but these patterns were not correlated with specific clinical manifestations. These results suggest that quantitative and qualitative aspects of anti-La responses in Sjögren's syndrome are determined by factors distinct from those determining the clinical expression of disease.
3261608 Sjögren's syndrome: a study of its neurological complications. 1988 Aug A detailed retrospective study of 105 patients with Sjögren's syndrome (50 primary and 55 secondary cases), showed that 31 had vasculitis and 18 had neurological abnormalities which after full investigation were not attributable to other causes. Most of the neurological symptoms were mild and when found in patients with secondary Sjögren's syndrome were more characteristic of the underlying autoimmune rheumatic disease. We found no significant association between the frequency of either vasculitis or any autoantibodies and the presence of neurological disease, but did confirm a significant association between vasculitis and the presence of antibodies to extractable nuclear antigens. We therefore question whether severe and relapsing neurological disease is common in patients with Sjögren's syndrome.
3260845 Decreased interleukin-1 responsiveness of blood lymphocytes in patients with primary Sjög 1988 Jan Impaired immune regulation is considered to be involved in the pathogenesis of primary Sjögren's syndrome (primary SS). A qualitative T lymphocyte defect is suggested by previous reports of impaired lymphocyte proliferation, impairment of interleukin-2 (IL-2) production, and a decreased number of IL-2 receptors, whereas the capacity of monocytes to produce IL-1 is normal in most patients. We here report on the IL-1 sensitivity of monocyte-depleted mononuclear cells (MDC) from patients with primary SS. IL-1 responsiveness, evaluated by measuring the enhancing effect of an IL-1 standard on the proliferative response of the patient's MDC, was decreased compared to that of the control group, and there was a positive correlation between patients' IL-1 production and IL-1 sensitivity. The results confirm the notion of impaired T lymphocyte function in primary SS, and suggest a pathogenetic mechanism that involves both monocytes and T lymphocytes.
1983326 [Necrotizing vasculitis of the panarteritis nodosa type in a long-course primary Sjögren' 1990 Oct Vasculitis is a complication happening in a third of patients with primary Sjögren's Syndrome. It can be of 2 types: neutrophilic or mononuclear and sometimes mixed. Very occasionally, a necrotizing vasculitis polyarteritis nodosa type during the evolution of Sjögren's Syndrome has appeared. A case of a female patient with a Sjögren's Syndrome of large evolution, who suddenly showed a poly-systemic affliction (nervous system, kidneys, muscles and digestive system) secondary to a necrotizing vasculitis type polyarteritis nodosa with a good response to immunosuppressors, is presented.
3037399 [Unilateral sensory neuropathy of the trigeminal nerve as the leading symptom of primary S 1987 Apr We report a case who presenting with a progressive numbness and mild hyperpathia in the second cutaneous division of the left trigeminal nerve as the leading symptom of Primary Sjögren's Syndrome. Further typical features of this autoimmune disorder are keratoconjunctivitis sicca and xerostomia. A symmetrical, predominantly sensory polyneuropathy can be revealed by sensory nerve conduction studies of the median and sural nerves. Laboratory findings mostly include elevated erythrocyte sedimentation rate, hypergammaglobulinemia and hypercomplementemia. The presence of the precipitating antinuclear antibodies SS-A and/or SS-B is pathognomonic for Sjögren's Syndrome. As long as the disease remains benign, treatment should be symptomatic. Malignant exacerbations require immunosuppressive treatment.
1747700 Primary Sjögren's syndrome in north east England--a longitudinal study. 1991 Dec We have documented the initial clinical features of 100 patients with primary Sjögren's syndrome (SS) together with the results of their baseline investigations. The evolution of the disease in these patients has been followed for a median of 34 months (range 3-84 months). The majority of patients were females aged 40-60 years, and common clinical features included eye symptoms (100%), xerostomia (100%), polyarthralgia (94%), Raynaud's phenomenon (81%) and salivary gland swelling (47%). Thyroid disease was relatively common (14%) while other endocrine disease was rare. Four patients died during follow-up, and three cases of lymphoma were detected. Other serious complications included pericarditis (10%), pleuroparenchymal lung disease (9%), renal tubular acidosis (3%) and cerebrovascular accidents (2%). The presence of anti-Ro antibodies identifies patients with more severe systemic disease. Spontaneous improvement occurred in 12 patients, while steroids were required for specific complications in 18. Overall, although lymphoma was found to excess in our group, the high mortality reported with primary SS elsewhere was not seen.