Browse

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

ID PMID Title PublicationDate abstract
1516379 Systemic amyloidosis secondary to chronic leg ulcers. 1992 Jul Chronic leg ulcers due to any cause are almost invariably associated with an inflammatory process. As with any long-standing inflammation, leg ulcers may be complicated by systemic amyloidosis, which occurs in rheumatoid arthritis, cystic fibrosis, tuberculosis, and other disorders. There are, however, very few reports on the association between these two conditions. We report a patient with severe leg ulcers of twenty years' duration in whom reactive systemic amyloidosis presented as a nephrotic syndrome.
1576317 [Fibromyalgia syndrome]. 1992 Feb The Fibromialgia Syndrome (FS) is a common clinical entity which may produce symtoms and signs related to multiple fields of Medicine. Typical clinical characteristics of FS include extensive pain, presence of sensitive points during exploration, morning stiffness, asthenia and non-refresing sleep. Frequently, associated rheumatologic diseases are observed, as rheumatoid arthritis, osteoarthrosis and vertebral disorders. In FS, complementary tests are usually normal. The most widely accepted hypothesis suggests that this is a disorder affecting modulation of pain sensitivity.
10163635 The cornea and systemic diseases. 1996 Aug Multiple systemic diseases imply corneal involvement. Corneal pathology may also be a presenting sign or may herald a forthcoming relapse of chronic disease. The presence of ulcerative keratitis in patients with rheumatoid arthritis can be associated with systemic lethal vasculitis. Epithelial fragility of the cornea is correlated to the presence of diabetic retinopathy. Rarely, interstitial keratitis may be the presenting sign of sarcoidosis. Corneal involvement in oculomucocutaneous syndromes continue to present a therapeutic challenge. Infectious and possibly drug-induced corneal pathology is a recurrent problem in patients with AIDS.
8347446 Pericardial effusion--an uncommon complication of Salmonella enteritis. 1993 May A 62-year-old lady who was receiving corticosteroids for rheumatoid arthritis was admitted suffering from dehydration due to salmonella enteritis. Despite rehydration and appropriate chemotherapy she remained unwell and developed hypotension and elevation of her jugular venous pressure. Echocardiography and subsequent aspiration demonstrated a purulent pericardial effusion from which S typhimurium was cultured. Following aspiration and a change of antibiotic therapy, her condition improved dramatically.
11173599 An in vitro Model for Studying Mechanisms Underlying Synoviocyte-Mediated Cartilage Invasi 1996 Rheumatoid arthritis (RA) is a chronic inflammatory disease of joints involving the pathological development of an invasive and destructive pannus tissue which contributes to the loss of cartilage and bone. To further analyze the process of cartilage degradation and invasion, we have developed an in vitro model composed of cartilage matrix and synoviocytes (isolated from RA pannus tissue, as well as normal synovial membrane). The matrix is derived from pig articular cartilage and contains collagen type II and proteoglycans and is similar in composition to human cartilage. Data generated from this model reveal that synoviocytes isolated from RA pannus tissue invaded cartilage matrix in a manner which directly correlated with the severity of the disease. Analysis of mechanisms associated with the invasive process demonstrate that highly invasive RA synoviocytes maintain a round morphology during attachment and spreading on cartilage matrix, compared with their normal counterparts. Furthermore, the level of secretion of matrix metalloproteinase (MMP) activity was shown to correlate with the RA phenotype, which could be modulated with a novel MMP inhibitor. Normal synoviocytes could be "converted" to an RA phenotype by specific inflammatory cytokines, such that invasion of cartilage matrix was augmented by culturing these cells in the presence of 5 U/ml IL-1b or 18 U/ml TGFb. Invasion was inhibited by 150 U/ml TNFa, and unaffected by 100 ng/ml PDGF. In addition, synovial fluid from RA patients induced invasion of normal synoviocytes, in a concentration dependent manner, from 150% to 460%; however, synovial fluid from another inflammatory arthritidy (Crohn's) did not augment invasion to the same degree. Moreover, this "conversion effect" appears to be specific for synoviocytes, since similar effects could not be achieved with human skin fibroblasts. This in vitro model of synoviocyte-mediated cartilage invasion allows for further molecular characterization of the invasive properties of the synoviocyte which contribute to RA.
8873636 Neuroimmune mechanisms in health and disease: 2. Disease. 1996 Oct 15 In the second part of their article on the emerging field of neuroimmunology, the authors present an overview of the role of neuroimmune mechanisms in defence against infectious diseases and in immune disorders. During acute febrile illness, immune-derived cytokines initiate an acute phase response, which is characterized by fever, inactivity, fatigue, anorexia and catabolism. Profound neuroendocrine and metabolic changes take place: acute phase proteins are produced in the liver, bone marrow function and the metabolic activity of leukocytes are greatly increased, and specific immune reactivity is suppressed. Defects in regulatory processes, which are fundamental to immune disorders and inflammatory diseases, may lie in the immune system, the neuro endocrine system or both. Defects in the hypothalamus-pituitary-adrenal axis have been observed in autoimmune and rheumatic diseases, chronic inflammatory disease, chronic fatigue syndrome and fibromyalgia. Prolactin levels are often elevated in patients with systemic lupus erythematosus and other autoimmune diseases, whereas the bioactivity of prolactin is decreased in patients with rheumatoid arthritis. Levels of sex hormones and thyroid hormone are decreased during severe inflammatory disease. Defective neural regulation of inflammation likely plays a pathogenic role in allergy and asthma, in the symmetrical form of rheumatoid arthritis and in gastrointestinal inflammatory disease. A better understanding of neuroimmunoregulation holds the promise of new approaches to the treatment of immune and inflammatory diseases with the use of hormones, neurotransmitters, neuropeptides and drugs that modulate these newly recognized immune regulators.
8879203 Proteasome alpha-type subunit C9 is a primary target of autoantibodies in sera of patients 1996 Oct 1 Autoantibodies occur in low frequencies among patients with myositis characterizing only distinct subsets of this disease. Most of these known antibodies are directed to enzymatically active complexes. The 20S proteasome represents an essential cytoplasmatic protein complex for intracellular nonlysosomal protein degradation, and is involved in major histocompatibility complex class I restricted antigen processing. In this study we investigated whether the 20S proteasome complex is an antibody target in myositis and in other autoimmune diseases. 34 sera of poly/dermatomyositis patients were assayed for antiproteasomal antibodies using enzyme-linked immunosorbent assay, immunoblot, and two-dimensional non-equilibrium pH gradient electrophoresis (NEPHGE). Sera was from patients with systemic lupus erythematosus (SLE), mixed connective tissue disease, and rheumatoid arthritis; healthy volunteers served as controls. In 62% (21/34) of the cases sera from patients with myositis and in 58% (30/52) of the cases sera from patients with SLE reacted with the 20S proteasome. These frequencies exceeded those of sera from patients with mixed connective tissue disease, rheumatoid arthritis, and healthy controls. The alpha-type subunit C9 of the 20S proteasome was determined to be the predominant target of the autoimmune sera in myositis and SLE. Lacking other frequent autoantibodies in myositis, the antiproteasome antibodies are the most common humoral immune response so far detected in this disease entity.
8081558 Expression and characterization of cM-T413, a chimeric anti-CD4 antibody with in vitro imm 1994 Jul Anti-CD4 monoclonal antibodies (mAbs) have shown considerable promise in the treatment of rheumatoid arthritis, psoriasis, and allograft rejection and may have potential use in blocking HIV-1 infection. One such anti-CD4 mAb we have developed, chimeric M-T412 (or cM-T412), has been used in clinical trials to treat rheumatoid arthritis, generalized postular psoriasis, and other autoimmune diseases. Here we report the cloning and expression of a second chimeric anti-CD4 mAb using M-T413, a murine mAb that blocks HIV-1 infection of H9 cells. We cloned the immunoglobulin light and heavy chain variable regions of M-T413, combined them with the human kappa (light chain) or G1, G2, G3 and G4 (heavy chain) constant regions in human expression vectors, and expressed these chimeric mAbs in 653 cells. Like chimeric M-T412 IgG1, the chimeric M-T413 mAbs inhibit T-cell proliferation in the mixed lymphocyte response and thus can act to immunosuppress CD4+ T-cell response. In contrast to M-T412, however, the M-T413 chimeric mAbs have reduced activity in an antibody-dependent cell-mediated cytotoxicity (ADCC) assay using human CD4+ target and effector cells. We conclude that the chimeric M-T413 mAbs have potential utility in treating autoimmune disease and may be useful as prophylactics in preventing HIV-1 infection.
7514978 Hyaluronic acid. A review of its pharmacology and use as a surgical aid in ophthalmology, 1994 Mar Hyaluronic acid is a naturally occurring polysaccharide with distinct physicochemical properties which underlie its application as a viscoelastic tool in ophthalmological surgery. In cataract surgery the role of hyaluronic acid in facilitating procedures and protecting the corneal endothelium is well established. Some benefit has also been gained with the use of hyaluronic acid in penetrating keratoplasty, trabeculectomy, retinal reattachment and trauma surgery, although its efficacy in these indications is less well-defined in the published literature. In addition to its lubricating and cushioning properties, demonstration of some in vitro anti-inflammatory activity and a possible disease-modifying effect for hyaluronic acid in animals has prompted its investigation as a treatment in osteoarthritis and, to a much lesser extent, in rheumatoid arthritis. Hyaluronic acid 20 mg, as weekly intra-articular injections for 3 to 7 weeks, improved knee pain and joint motion in patients with osteoarthritis. Although this occurred to a greater degree than with placebo in most comparisons, the effects of hyaluronic acid was similar to those of placebo in the largest trial. In the few available comparisons with other agents, hyaluronic acid appeared equivalent to methylprednisolone 40 mg (for 3 weeks) and to a single injection of triamcinolone 40 mg. Hyaluronic acid was distinguished from other therapies by providing a sustained effect after treatment discontinuation. Together with its very good tolerability profile, these properties justify further study of hyaluronic acid in patients with osteoarthritis. Some limited evidence of improvement in patients with rheumatoid arthritis, and a possible healing effect of hyaluronic acid on tympanic membrane perforations, represent additional areas of interest for future investigation. In summary, hyaluronic acid is a well-established adjunct to cataract surgery and may prove to be a promising option in the treatment of patients with osteoarthritis. Its very good tolerability provides further impetus for examination of its potential role in an extended scope of arthritic and ophthalmological indications, and in wound healing.
1281763 A one-step sandwich enzyme immunoassay for human matrix metalloproteinase 3 (stromelysin-1 1992 Oct 15 A one-step sandwich enzyme immunoassay (EIA) for matrix metalloproteinase 3 (MMP-3; stromelysin-1) was developed. The assay system used two simultaneous immunoreactions using a solid phase monoclonal antibody and a horseradish peroxidase-labeled monoclonal antibody (Fab'). The sensitivity of the assay system was 20 micrograms/l and linearity was obtained between 31 and 500 micrograms/l. The EIA system was capable of measuring both precursor and active forms of MMP-3 as well as the forms of MMP-3 complexed with tissue inhibitors of metalloproteinases. MMP-3 levels as measured by this assay are significantly higher in the sera of patients with rheumatoid arthritis as compared to those of healthy subjects and patients with osteoarthritis. Immunoblot analyses showed that in the sera and synovial fluids of patients with rheumatoid arthritis, MMP-3 is present in the 59- and 57-kDa precursor forms.
7770728 Human IgG rheumatoid factors and RF-like immune complexes induce IgG1 rheumatoid factor pr 1995 Jun The synovial fluid of patients with rheumatoid arthritis (RA) was found to contain IgG and/or IgG-containing immune complexes (ICs) that stimulated an intense antibody formation when injected into mice of certain strains, notably of NZ background. The response was characterized by high and sustained levels of IgG1 antibodies with rheumatoid factor (RF) activity. In the study described, we investigated whether it is the antibodies with RF activity in the synovial fluid, that are responsible for stimulation of mouse RF in vivo. Different mouse strains were injected with synovial fluid from a seropositive RA patient (RA-SF), with human monoclonal antibodies with RF activity, with a human non-RF monoclonal antibody or with different preformed RF-like antibody-antibody (Ab-Ab) ICs. The experimental mice were monitored subsequently for IgG1 RF production. IgG1 RF antibodies were found in all strains (NZB, BALB/c and CBA) injected with Ab-Ab ICs formed at equivalence, but only in NZB using RA-SF or human monoclonal antibodies with RF activity. Optimal production of IgG1 RF by Ab-Ab ICs required the integrity of Fc and F(ab)'2 portions respectively of the antibodies; soluble and truncated ICs were less effective. Further studies demonstrated that the IgG1 RF response was not simply the result of a specific immune response against human IgG, since humoral immunity against human IgG was induced only when combined with an efficient adjuvant. During a typical adjuvant-associated primary response specific antibodies of IgM, IgG1 and IgG2a isotypes were found, i.e. quite different from the selective IgG1 response induced by RF-like containing immune complexes. This conclusion is substantiated further by the clear differences in responses to IgG containing fraction obtained from RA-SF in NZ mice compared to other strains. Our findings argue for a different type of reaction leading to the selective IgG1 response and might aid in elucidating the mechanisms for chronic production of antibodies with RF activity in patients with RA.
7488551 Suppression of pannus-like extension of synovial cells by lipid-derivatized chondroitin su 1995 Oct In rheumatoid arthritis, pannus formation resulting from synovial inflammation is a major factor in cartilage destruction. The ability of arthritic synovial cells to undergo pannus formation depends upon their initial adhesion to the partially deformed cartilage surfaces. Our recent studies using various lipid-derivatized glycosaminoglycans have revealed a preeminent inhibitory activity of phosphatidyl ethanol amine-derivatized chondroitin sulphate (CS-PE) toward cell-matrix adhesion. Here we evaluate whether CS-PE may protect articular cartilage from pannus extension in different in vitro and in vivo model systems using Escherichia coli 0:14-induced arthritis in rabbits and the articular cartilage explants, synovial tissues, and synovial cells obtained from them. These studies showed that CS-PE suppressed the in vivo pannus-like extension on cartilage surfaces, as well as the in vitro extension of the synovial cell layer on both CS-PE treated culture plates and cartilage explants. The results suggest that native chondroitin sulphate proteoglycans in the surface of normal articular cartilage play an important role in protecting the tissues from pannus extension and that the CS-PE immobilized onto partially eroded cartilage can mimic the inhibitory action of native chondroitin sulphate proteoglycans.
8501748 An imaginative approach to synovitis--the role of hypoxic reperfusion damage in arthritis. 1993 Apr The rheumatoid joint is hypoxic. The loss of the physiologic defense mechanism, reflex muscle inhibition, allows the generation of high intraarticular pressures, particularly during exercise. Hypoxia alters the biochemistry of the synovium and encourages the production of reactive oxygen species (ROS) on reperfusion of blood. In excess, ROS damage tissues, and the products of oxidative damage are detectable in rheumatoid synovial fluid. In addition to damaging proteins, carbohydrates and lipids, cellular and structural damage also occurs.
7519647 Autoantibodies to human nuclear lamin B2 protein. Epitope specificity in different autoimm 1994 Sep 1 The nuclear lamina of mammalian cells consists of three major proteins, lamins A, C, and B, and a fourth minor protein, lamin B2. Lamins belong to the family of intermediate filaments and are highly similar both in structure and primary sequence. They are organized in three well-defined domains: 1) a central alpha-helical rod, which is a secondary structure shared by all types of intermediate filaments, formed by three alpha-helices (coils 1A, 1B, and 2) and surrounded by 2) an amino-terminal head and 3) a carboxyl-terminal tail. Autoantibodies toward major lamin have been described previously in sera from patients with different autoimmune diseases. We chose an epitope mapping approach to further characterize the autoimmune response to nuclear lamin. Different lamin B2 domains were expressed as fusion proteins with the glutathione S-transferase and then used in immunoblotting experiments to analyze sera from patients with autoimmune diseases (chronic active hepatitis, SLE, rheumatoid arthritis, and polymyalgia rheumatica) and from healthy subjects. At a 1:1000 dilution, none of the control sera recognized any of the recombinant polypeptides. Conversely, reactive sera were present in all groups of patients. The ability to recognize a protein domain seemed to differ with the pathology. Most chronic active hepatitis sera were reactive to two or more lamin domains and reacting SLE sera always gave positive signals to coil 2 and/or coil 1B. Coil 2 was preferentially recognized by rheumatoid arthritis sera. Polymyalgia rheumatica sera differed from all of the others because of their low reactivity to the rod domain and preference for the C terminus, a lamin-specific domain.
8037838 Autoantibodies to HMG-17 nucleosomal protein in patients with scleroderma. 1994 Apr Autoantibodies to HMG-17, a non-histone nucleosomal protein, were found in systemic lupus erythematosus (SLE), mixed connective tissue disease (MCTD) and ANA positive pauciarticular juvenile rheumatoid arthritis (JRA), but not in rheumatoid arthritis (RA). Using highly purified HMG-17 derived from porcine thymus, we tested sera from 50 patients with scleroderma for antibodies to HMG-17 by enzyme-linked immunosorbent assay (ELISA). There were 16 patients with diffuse cutaneous systemic sclerosis (dSSc) and 34 with limited cutaneous systemic sclerosis (1SSc) with age at disease onset 40.25 +/- 11.68 and 39.94 +/- 15.68 years, respectively, and disease duration 6.03 +/- 4.98 and 13.34 +/- 11.80 years, respectively (P < 0.0001). Anticentromere antibodies (ACA) were found in 65% of 1SSc patients but not in dSSc (P < 0.0001) while the prevalence of antinuclear antibodies (ANA) with other than ACA patterns did not differ in the two groups. Anti-HMG-17 antibodies occurred in 20 patients (40%), five with dSSc (31%) and 15 with 1SSc (41%). Twelve of the 20 HMG-17 positive patients were also positive for ACA (60%) but this association was not significant. No association was found between anti-HMG-17 and other antibody patterns. In conclusion, anti-HMG-17 antibodies occur in one third of scleroderma patients, do not discriminate scleroderma variants and are not associated with other autoantibodies.
1573300 An appraisal of enzyme linked immunosorbent assay (ELISA) and serum antibody competition t 1992 Jan Seventy-eight untreated leprosy patients, 104 treated patients and 105 healthy contacts were tested using two serological tests, SACT (serum antibody competition test based on competitive inhibition of monoclonal antibody binding to the MY2a determinant of M. leprae) and ELISA (measurement of IgM antibodies to the neoglycoproteins D-BSA and ND-BSA representing the phenolic-glycolipid antigen of M. leprae). The controls included normal healthy individuals, patients with sputum positive pulmonary tuberculosis, and active cases of rheumatoid arthritis from the department of rheumatology. The specificity of SACT was found to be very high. ELISA was found to be positive in two patients with rheumatoid arthritis, one each for D-BSA and ND-BSA ELISA. Both tests had a high sensitivity in BL and lepromatous patients. The sensitivity to both tests was considerably lower in tuberculoid and BT patients i.e., below 40%. Therefore the diagnostic value of a negative test in suspected cases of leprosy was very low employing either of the two tests. A proportion of patients with paucibacillary tuberculoid and BT leprosy were positive after six months or longer after therapy. Similarly a large number of BL and lepromatous patients were positive after considerably longer periods of treatment. The use of either tests for determining the duration of therapy is therefore limited. SACT appears to be more sensitive than ELISA with ND-BSA in detecting subclinical infection. The cumulative positivity of the two tests may be used as a measure of the infectivity of the disease in the community and for evaluating disease control methods.
7651066 [Uncemented endoprosthesis in a female patient with chronic juvenile monoarthritis of the 1995 Jan A case report of an 18 year-old female patient with juvenile rheumatoid monoarthritis (JRA) of the knee joint, whose treatment the authors have been following up during the last 14 years is presented. Previously known and reported difficulties and complications in the diagnosis of chronic juvenile rheumatoid monoarthritis are related with special reference to a specific case, a female patient in whose case the correct diagnosis and adequate treatment was begun three years after the first onset of symptoms. At the age of 15, the patient developed knee ankylosis of 20 degrees in flexion. Following this dezarthrodesis of the knee joint, cementless total knee arthroplasty was performed. The postoperative results are very encouraging, the knee joint is stable, the passive range of movement is 5/90 degrees, while the active range of motion is 10/80 degrees. Total knee arthroplasty helped to correct the previously present inegality of the lower extremities, while the problem of an exceptionally thick patella was resolved by coronary (frontal) osteotomy of the patella. The presented case once again confirms that in selected JRA patients cementless knee arthroplasty can achieve excellent results.
8082889 Time course of antibodies against IgG and type II collagen in adjuvant arthritis. Role of 1994 Feb The aim of this study was to elucidate, during the time course of adjuvant arthritis, the existence of antibodies directed to IgG (rheumatoid factor-like) and antibodies against type II collagen. In a second study, we also studied the relation between antibody production, arthritic process and mycobacteria administration. We have demonstrated the presence of antibodies to IgG and type II collagen by means of ELISA techniques. This reactivity appeared on day 7 post-induction, decreased later, and increased progressively from day 21 until last day studied (day 56 post-induction). We have also quantified antibodies against a soluble fraction of Mycobacterium butyricum, the inductor of the disease. Anti-mycobacteria antibodies appeared during the first seven days after induction, but from day 14, when systemic inflammation began, their levels suddenly increased. There is a positive correlation between anti-mycobacteria antibody levels and articular swelling. Anti-IgG and anti-collagen antibody production was not directly linked to arthritic process since these antibodies were synthesized when M. butyricum was administered intraperitoneally, which does not induce arthritis. Anti-mycobacteria antibody concentration was higher when arthritis induction by mycobacterial was successful than when it was unsuccessful.
8222315 Effect of pregnancy on proteoglycan-induced progressive polyarthritis in BALB/c mice: remi 1993 Nov Proteoglycan-induced arthritis is a murine autoimmune model displaying many similarities to human rheumatoid arthritis and ankylosing spondylitis, as has been documented by clinical, immunological and histopathological studies. Since the onset of arthritis correlates with the serum antibody level to mouse cartilage proteoglycan (PG), it is believed that these autoreactive antibodies may play crucial roles in the pathological mechanisms of PG-induced arthritis. We have found that fertility in these PG-induced arthritic mice had been reduced but, unlike collagen-induced arthritis, had not been completely lost. Moreover, pregnancy had a beneficial effect upon the clinical symptoms with very little or no influence on serum antibody levels. Although fertility was retained and arthritic mothers delivered healthy offspring, the birth frequency was significantly less than in non-arthritic age-matched controls. Furthermore, the presence of anti-PG autoantibodies (predominantly IgG1 subclass) transmitted from arthritic mothers to infants transplacentally and by milk during the lactation period did not render these offspring either resistant or more sensitive to subsequent induction of arthritis. Subsequent immunization of infants with 'arthritogenic' PG revealed an unaltered susceptibility to arthritis induction.
1537378 Homologous collagen-induced arthritis in rats and mice are associated with structurally di 1992 Feb Collagen-induced arthritis (CIA) in rats, induced with homologous type II collagen (CII), is a genetically more restricted disease and has better resemblance to rheumatoid arthritis by its chronic disease course, than CIA induced with heterologous CII. The DA strain is highly susceptible to CIA induced with homologous CII, while the Lewis strain is resistant. (DAxLew)F1 is susceptible and backcrossing to Lewis reveals a close, but not complete, association of both arthritis and CII responsiveness to the RT1a haplotype. Analyses of congenic strains on DA and Lewis backgrounds suggest that expression of a major histocompatibility complex class II Ba molecule, encoded from the RT1Ba locus, is associated with arthritis susceptibility and CII responsiveness. The second exons coding for the first domains of the alpha and beta chains of both the RT1a and RT1l haplotypes were sequenced and the deduced amino acid sequences compared with the corresponding molecule associated with susceptibility to CIA in the mouse (H-2 Aq). The sequences of the respective alleles revealed no obvious structural homology explaining the extensive similarities in the development of chronic autoimmune arthritis. Instead, this finding implies that different trimolecular constituents (i.e. class II, T cell receptor, and CII peptides) may yield an antigen presentation event that is able to trigger a similar autoaggressiveness in the two rodent species.