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

ID PMID Title PublicationDate abstract
6978717 Histone antibodies in systemic lupus erythematosus. A possible diagnostic tool. 1982 Apr Antibodies to total histones and histone fractions H1, H2a-H4, H2b, and H3 were measured in serum samples from 61 patients with systemic lupus erythematosus (SLE), 33 with rheumatoid arthritis, 17 with systemic sclerosis, and 20 with various other diseases by use of a sensitive immunoenzymatic assay. Histone antibodies were present in 52.4% of the SLE samples whereas only 1 of the samples from other diseases was positive (systemic sclerosis). The presence of these antibodies in SLE patients was not associated with any specific clinical manifestations, but was correlated with activity of the disease: 87% (20 of 23) of patients with active SLE, in particular 9 of 9 not yet treated, showed histone antibody whereas only 18% (4 of 22) of samples from patients with inactive SLE were positive. We believe that the measurement of histone antibodies would be a useful addition to the present laboratory parameters (antinuclear and double-stranded DNA antibodies and circulating immune complexes) for the diagnosis and progression of systemic lupus erythematosus, particularly since they seem to appear during or just before the onset of an active phase and tend to be absent during remission.
1163990 Laboratory diagnosis of degenerative joint disease. 1975 Jul Degenerative joint disease (DJD) is characterized by pain on use. X-rays show cartilage narrowing and osteophytes. Synovial effusions are non-inflammatory, i.e. clear wiht good viscosity and less than 2000 WBC per mm. 3 Cartilage fragments may be seen in the joint fluid. Important systemic diseases that can cause degenerative joint disease include ochronosis, hemochromatosis, hyperparathyroidism, acromegaly, Ehlers-Danlos syndrome, diabetes and syphilis with their neuropathic joints, Wilson's disease and hypothyroidism. The late results of other diseases such as rheumatoid arthritis and aseptic necrosis may resemble DJD.
6240113 Demonstration of a helper factor(s) with T-cell-replacing activity in synovial fluid. 1984 Dec Cell-free synovial fluid (SF) obtained from patients with rheumatoid arthritis contains a helper factor(s) capable of augmenting the generation of plaque-forming cells (PFC) in pokeweed mitogen (PWM)-stimulated normal peripheral blood mononuclear cells (PBMC). This helper factor behaves like a polyclonal B-cell activator, in that it triggers the formation of IgM, IgG, and IgA PFC. However, SF has little or no effect on the proliferation of PWM-activated PBMC. Furthermore, SF was capable of replacing T cells for PWM-induced differentiation but not proliferation of enriched human blood B lymphocytes. No helper factor or T-cell-replacing activity was found in SF from patients with traumatic synovitis. Fractionation of SF containing helper activity on staphylococcal protein A column indicated that the activity is induced by biologically active molecules distinct from materials that preferentially bind to protein A such as IgG immune complexes. We conclude that the present activity has striking similarities to the recently described B-cell differentiation factor that is produced by specifically activated T-cell lines in vitro.
7198342 [Activity of plasminogen activators and plasmin inhibitors in the joint capsule in various 1981 Oct The activity of plasminogen activators and plasmin inhibitors in articular capsules of the hip and knee joints in rheumatoid arthritis, chronic traumatic inflammation, arthrosis and aseptic loosening of prosthesis was determined histochemically and correlated with the degree of mobility in osteoarthrosis of the hip. Microscopically unchanged articular capsules were employed as reference sites. In inflammatory articular diseases the plasminogen activator activity was significantly reduced, whereas it remained unchanged in arthrosis and necrosis of the heas of the femur, and significantly enhanced in aseptic loosening of prosthesis. Plasmin inhibitor activity was established in joint capsules with inflammatory changes only; in case of rheumatic inflammation, it was higher than with traumatic inflammation. In osteoarthrosis of the hip there is a positive correlation between joint mobility and plasminogen activator activity. The results point towards involvement of the local fibrinolytic system in joint diseases; however, no definite statement can be made with regard to possible causative linkups.
6236014 The effect of low doses of prednisolone on the traffic of T helper-inducer cells in rheuma 1982 Sep The effects of a single dose of 5 and 10 mg of prednisolone on the kinetics of lymphocytes and T lymphocyte subsets were investigated in patients suffering from active rheumatoid arthritis. Six hours after intake of 10 mg of the drug a significant drop in total lymphocyte count, total T-cell numbers and T-helper cell numbers was recorded. The values returned to baseline values within 24 hours. Intake of 5 mg of prednisolone depressed total T-cell count and more particularly the absolute numbers of T-helper cells. No statistically significant changes occurred in T suppressor-cytotoxic cell traffics. The influence on the kinetics of T-helper cells was responsible for a significant decrease of helper/suppressor ratios in the intravascular compartment.
913119 Serum concentrations of flurbiprofen in rheumatoid patients receiving flurbiprofen over lo 1977 Serum concentrations of flurbiprofen were measured following single oral doses of 50 mg to 200 mg in patients who previously had received flurbiprofen over long periods of time. The apparent elimination half-lives in groups of patients who received different doses were not significantly different from each other nor from the value previously obtained in a group of healthy volunteers given a single oral dose of 50 mg. Areas under serum concentration versus time curves were linearly related to dose over the range of doses examined. The results indicate that the pharmacokinetics of flurbiprofen are not significantly dose-dependent over the range of doses studied and that administration of relatively high doses of flurbiprofen over long periods of time neither induces nor inhibits flurbiprofen metabolism.
6381253 Studies on the binding of complement factor C3 to the surface of human blood platelets. 1984 Employing immunofluorescent staining methods, platelets from several adult patients with chronic idiopathic thrombocytopenic purpura, with systemic lupus erythematosus, and with classical rheumatoid arthritis stained positively with antisera to C3(beta 1C) and C3dg(alpha 2D). In some cases, platelet-bound C3dg antigens, but no evidence of other C3 antigens were observed. Platelets that were positive for C3 and/or C3dg were always positive for IgG or for both IgG and IgM. Platelets from normal subjects stained negatively for C3, C3dg, IgG, and IgM. Furthermore, various incubation experiments were performed to investigate the uptake of C3 and its subfragments on normal platelets. Positive platelet staining for C3 was obtained after incubation with normal and C3b-containing sera, but not after incubation with native C3. Platelets incubated with C3c(beta 1A)/C3dg-containing serum gave a positive staining for C3dg, but not for C3c. None of the sera stained positively for IgG or IgM. Thus, in contrast to platelets from several of the patients, no in vivo binding of C3 antigens on normal platelets could be established. However, in vitro they could take up both C3b and C3dg, apparently by specific binding to platelet surface structures.
6245127 Interactions among rheumatoid synovial cells and monocyte-macrophages: production of colla 1980 Apr Adherent synovial cells (ASC) were obtained from minced synovium from patients with rheumatoid arthritis by dissociating the lining cells from the extracellular matrix and dispersing them with proteases. These cells produce high levels of latent collagenase in primary culture. With passage of ASC, collagenase levels decrease but can be stimulated by a soluble factor (MCF) released in vitro from cultured human blood monocyte-macrophages. Monocyte cultures exposed to aggregated immunoglobulin, Fc fragments of immunoglobulin or concanavalin A (Con A) increase production of MCF several-fold more than the control cultures. MCF production by monocytes exposed to Fab fragments does not differ from controls. Although aggregated immunoglobulin, Fc fragments, and Con A stimulate PGE2 synthesis and secretion by human monocytes, the effects on MCF production are not mediated by PGE2 since concentrations of indomethacin that completely block PGE2 production do not inhibit MCF production. These findings of increased production of MCF by monocytes in response to substances that probably exert their effects via surface receptors could be relevant in interpreting the in vivo role of immune complexes in diseases associated with connective tissue destruction.
6294815 Inflammatory responses to intradermal crystals in healthy volunteers and patients with rhe 1982 The inflammatory response to intradermal injections of urate, pyrophosphate and hydroxyapatite crystals in human forearm skin is described. Patients with rheumatoid arthritis responded normally to urate crystals, and patients with osteoarthritis or pyrophosphate arthropathy responded normally to hydroxyapatite and pyrophosphate crystals respectively. These results suggest that variation in host response to crystals cannot explain the different patterns of crystal-induced disease seen in man. The model, however, is recommended as a safe, simple ethical and reproducible test of inflammation in human subjects.
7014063 Catabolin--a cartilage catabolic factor from synovium. 1981 May Resorption of cartilage matrix is usually considered to be due to extrinsic proteases, generally thought to be the neutral metalloproteases, including collagenase. Such enzymes can be secreted from synovial tissue and in acute forms of arthritis they are believed to be the main agents of pannus erosion. However, such enzyme secretion has not been clearly demonstrated to be the causative agent in either rheumatoid arthritis or in osteoarthritis. For example, no specific inhibitors of these proteinases have yet been proved effective in vivo. Recent experiments at the Strangeways Research Laboratory have demonstrated that viable chondrocytes of animal and human articular cartilage are capable of resorbing their surrounding matrix without the aid of extrinsic enzymes. We now know that such resorption can be stimulated by the action of a low molecular weight peptide released from living synovial and other connective tissues. These messengers (catabolins) are capable of stimulating chondrocytes to degrade totally both proteoglycan and collagen. The purification, properties, regulation and action of catabolism are under investigation to determine the role for catabolin in arthritis.
3879317 [HLA B27-associated rheumatic diseases from the clinical viewpoint]. 1985 Dec On the basis of the description of the possible variable courses and symptoms of ankylosing spondylitis, Reiter's syndrome, and reactive arthritides (spondarthritides) frequently produced by intestinal infections, all of which show HLA B27 as the predisposing hereditary antigen in about 90% of the cases, it is discussed whether these conditions represent a disease entity in which additional unknown factors determine the expression and the tendency of the course of the disease.
984900 Psoriatic arthritis. Follow-up study. 1976 Jun 227 patients with psoriasis and various forms of arthritis have been kept under review. Psoriasis and inflammatory arthropathy was present in 168 patients, of whom 94 have been followed up for more than 10 years. An arthritis indistinguishable from rheumatoid disease was present in 78%, distal joint arthritis in 16-6%, and deforming arthritis in 4-8%. There was a female predominance in the sex ratio of patients, although males predominated in the distal joint group (male:female 1-5:1). The peak age of onset was between 36 and 45 years, although in the deforming group the arthritis began before the age of 20 three times as commonly as it did in the indistinguishable group. Onset was acute in nearly half of the patients. At onset the distal joints were affected in one-third of the distal joint group. A synchronous onset of skin and joint changes was uncommon. Skin lesions usually preceded the arthritis but occurred after onset in 16%. Apart from in the deforming group, the arthritis was mild, judged by the number of admissions to hospital for treatment of the joint disease, and the time off work. Deterioration clinically and radiographically occurred in only a small portion of the distal joint and indistinguishable groups. Antimalarial drugs have been used in 7 patients, with deterioration of the skin condition in 4. Uveitis occurred particularly in the men of all three groups, but was most frequent in those with deforming arthritis. A family history of psoriasis was obtained in 26% of first-degree relatives and 13% of second-degree relatives. A history of polyarthritis was most common in patients in the deforming group. The sheep cell agglutination test was negative in the majority, but was positive in 16% of the indistinguishable group, fluctuating in a further 10%. A small number of joints only deteriorated radiographically (10% of the distal and indistinguishable groups). The men in the distal group showed greater radiographic changes and more deterioration in the terminal interphalangeal joints of the fingers than the women. Similarly they showed more deterioration of the metatarsophalangeal joints than the women. 18 patients died, one with gastric haemorrhage resulting from treatment of exfoliative psoriasis with immunosuppressive therapy, and 2 from bronchopneumonia thought to be related to immobility caused by the arthritis.
7016448 A single-blind crossover trial of the anti-inflammatory drug sodium meclofenamate and plac 1981 A single-blind crossover trial was carried out in 21 patients with active rheumatoid arthritis to assess the effectiveness and tolerance of sodium meclofenamate (300 mg per day) compared with placebo. After a 1-week washout period patients had two periods of active medication, each of 2 weeks, separated by 1 week on placebo. Morning stiffness, walking speed, pain score, patient impression of response, joint tenderness and power, work and maximum grip strength achieved by hand grip were all improved by sodium meclofenamate and an anti-inflammatory effect of the drug was demonstrated, with some reduction in the swelling of PIP joints. There was no advantage in assessing pain on full movement of the small joints of the hands in addition to direct tenderness. Power, work and rate of grip release achieved during hand grip provided more information about hand function than maximum grip strength alone. Lymphocyte transformation to non-specific mitogens was enhanced by the drug. Twelve patients had some form of gastro intestinal complaint during the study and it is suggested that diarrhoea is likely to prove to be the major limiting factor of acceptance by some patients.
6096543 Neurologic complications associated with gold therapy for rheumatoid arthritis. 1984 Oct Neurologic complications of gold are rare and include peripheral neuropathy, a Guillain-Barré-type syndrome, cranial nerve palsies and encephalopathy. Three cases of cranial neuropathy complicating chrysotherapy for rheumatoid arthritis are described. One also had a sensorimotor neuropathy associated with segmental demyelination and axonal degeneration, and another developed an encephalopathy which, on contrast enhanced computed tomographic scanning, showed reversible cerebral and cerebellar white matter lesions. Early recognition and prompt withdrawal of chrysotherapy are the mainstay of management of this lesser known complication.
6182782 Detection of human antinuclear antibodies on rodent omenta. 1982 Detection of antinuclear antibodies in the sera of patients by immunofluorescence using mouse or rabbit omentum is recommended, because artifacts stemming from cryostat sectioning and thawing the tissue are eliminated and the advantage of tissue-bound evenly spread cells is preserved. Moreover, the technique is sensitive and permits reading on easily recognizable cell types.
11718 Cutaneous necrotizing vasculitis and related disorders. 1976 Nov Leukocytoclastic vasculitis of the skin comprises several distinct clinical syndromes, each with immune complex deposition and some form of complement activation. Necrotizing vasculitides of larger blood vessels also produce skin lesions. These can be distinguished morphologically from those of small vessel vasculitis. Analysis of the features of these lesions is discussed.
930944 Penicillamine-associated myasthenia gravis, antiacetylcholine receptor and antistriational 1977 Nov Myasthenia gravis with thymic hyperplasia developed in a patient with Wilson's disease after eight years of penicillamine treatment. Four months prior to the onset of myasthenia, penicillin hypersensitivity was observed. Immunofluorescence on the excised thymus revealed immunoglobulin and complement deposition, but the myasthenia persisted after thymectomy and continuation of penicillamine therapy. Increased antiacetylcholine receptor antibody was demonstrable throughout. This patient subsequently became pregnant, enabling studies to be performed on the transplacental transfer of the immunoglobulin G (IgG) class antiacetylcholine receptor antibody. Eleven cases of rheumatoid arthritis with penicillamine-associated antistriational antibodies have also been observed; in three of these cases there was evidence of myasthenia gravis. These observations extend earlier reports of the association of penicillamine with myasthenia gravis and suggest that antistriational antibody, antiacetylcholine receptor antibody and thymic hyperplasia may be independent effects of penicillamine therapy.
6383669 Detection of IgG rheumatoid factor secreting cells in autoimmune MRL/1 mice: a kinetic stu 1984 Oct The kinetics of appearance of cells secreting IgG rheumatoid factor (IgG RF) has been studied in MRL/l mice by means of the ELISPOT assay, a new immunoenzyme procedure. Mice of the MRL/l strain spontaneously develop an autoimmune disease associated with arthritic manifestations. IgG RF secreting splenocytes were first detected at the clinical onset of the disease at the age of 3 months. Peak frequencies of IgG RF secreting cells amounting to almost 10% of the total number of IgG secreting cells were observed at later stages. The appearance of IgG RF secreting cells was preceded by at least 1 month by elevated levels of circulating immune complexes and abnormally high numbers of IgG secreting cells. The frequencies of IgG RF secreting cells and of IgG secreting splenocytes did not follow each other at least not during the first 3 months preceding the onset of clinical disease. The data presented suggest that IgG RF production in MRL/l mice is not triggered as part of an early stage of polyclonal activation but could be induced by IgG containing immune complexes.
6406611 A solid phase radioimmunoassay for detection of antibodies to extractable nuclear antigens 1983 Jun 24 A solid phase radioimmunoassay is described for the detection of autoantibodies to the saline-soluble extractable nuclear antigens, ribonucleoprotein (RNP) and SS-B (or La). This assay depends on enrichment of antigens from a crude, commercially available (Pel Freez, U.S.A.) extract of rabbit thymus by absorption to the F(ab)2 fraction of specific high titre antibody attached to a microtitre plate. Serum antibody reactive with this antigen is then detected by 125I-labelled Protein A. The assay is simple and is more sensitive than the gel diffusion assays in general use for detecting such antibodies.
6120390 Non-steroidal anti-inflammatory agent inhibit the synthesis of IgM rheumatoid factor in vi 1982 Mar 6 The effects of three non-steroidal anti-inflammatory agents, indomethacin, carprofen, and piroxicam, on in-vitro IgM rheumatoid-factor (IgM-RF) production by peripheral-blood mononuclear cells were studied in lymphocytes isolated from the peripheral (age 20-40 years) and elderly (age 70-80 years) volunteers selected for their known in-vitro IgM-RF production. All three drugs in therapeutic concentrations inhibited IgM-RF production approximately 50%. Addition of low doses of prostaglandin E2 (PGE2) (30 nmol/l) to the cultures containing indomethacin restored the IgM-RF production to the original levels. Neither indomethacin nor PGE2 had any effect on IgM-RF production if the T cells were irradiated before culture. Endogenous PGE2 seems to stimulate IgM-RF production through an effect on a radiosensitive T-cell population. Non-steroidal anti-inflammatory agents block PGE2 production and therefore reduce IgM-RF production in vitro. These results suggest a new mechanism for the beneficial effect of prostaglandin synthetase inhibitors in the treatment of rheumatoid arthritis.