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

ID PMID Title PublicationDate abstract
2870582 Connective tissue components in synovial fibroblast cultures exposed to interleukin 1 and 1986 Long-term synovial fibroblast cultures were exposed to interleukin 1 (IL-1) or prostaglandin E2 (PGE2). The normally spindle-shaped fibroblasts changed to stellate-shaped cells, resembling the HLA-DR-positive, collagenase-producing cells which are normally seen only in primary cultures from enzyme-digested rheumatoid synovial tissue. However, the IL-1- or PGE2-induced fibroblasts were not HLA-DR-positive. This suggests that these cell populations represent originally different cell lines or that the expression of HLA-DR antigens is not induced by the agents used. For further characterization of these stellate cells, the location of fibronectin and type I collagen was studied by specific antibodies and the pericellular coat around fibroblasts was visualized by the erythrocyte exclusion method. Both IL-1 and PGE2 treatments destroyed the intercellular fibronectin network. Type I collagen was detected as intracellular granules. The stellate fibroblasts were usually full of these granules in contrast to intact fibroblasts in which the number of collagen fluorescence granules varied greatly. The pericellular coat known to be formed mainly by hyaluronic acid was similar around spindle and stellate-shaped fibroblasts. Rheumatoid arthritis-derived fibroblasts did not differ from their non-rheumatoid counterparts in any of the experiments. The effect of IL-1 and PGE2 on fibroblasts simulates the interaction between mononuclear cells and fibroblasts in synovial stroma and also potentially the interactions between different cell types in synovial lining.
1673721 Toxicity profiles of disease modifying antirheumatic drugs in rheumatoid arthritis. 1991 Feb The toxicity profiles of 7 disease modifying antirheumatic drugs (DMARD) (hydroxychloroquine, intramuscular (im) gold, D-penicillamine, oral gold, methotrexate (MTX), azathioprine and cyclophosphamide) were evaluated in 2,479 patients with rheumatoid arthritis consecutively enrolled at 5 centers in the Arthritis, Rheumatism and Aging Medical Information System (ARAMIS) program. Incidence rates for side effects are reported as events/1000 patient-years. Our descriptive study revealed an individual profile of prevalent toxicities for each drug. Oral gold was characterized by substantial lower gastrointestinal (GI) toxicity (diarrhea 391 events/1000 patient-years, loose bowel movement 148, lower abdominal pain 76), MTX by hepatotoxicity (47) while D-penicillamine had the only clinically significant incidence of altered taste (40). MTX users reported the most mucosal ulcers (87), followed by oral gold (76), im gold (55) and D-penicillamine (38). Rash was frequently seen with gold compounds and D-penicillamine, while upper GI toxicity was common with immunosuppressive agents. Cyclophosphamide had 48% discontinuations within 6 months. MTX had the lowest discontinuation rate in the first 6 months, but then showed little difference from im gold. A preliminary similarity index was developed to compare the toxicity profiles of various DMARD. Close similarities were found between toxicity profiles of im gold and D-penicillamine, and between azathioprine and MTX. Oral gold had a unique toxicity pattern. Knowledge of these different toxicity patterns can enable more appropriate selection of agents for particular patients.
3757314 Detection of IgG-rheumatoid factor in sera of patients with acute poststreptococcal glomer 1986 Aug Rheumatoid factors (RF) were measured in sera from 75 patients with acute poststreptococcal glomerulonephritis (APSGN) and compared with normal controls, patients with rheumatoid arthritis in activity and acute rheumatic fever. Using two sensitive and specific solid phase radioimmunoassays, IgM-RF and IgG-RF were detected, respectively, in 15% and 32% of the patients with APSGN. A positive correlation (r = 0.37, n = 75, p less than 0.05) was obtained between serum levels of IgG-RF and circulating immune complexes determined by conglutinin assay. Chromatographic studies in serum from two patients with APSGN demonstrated that the circulating IgG-RFs were mainly free, not complexed. It is suggested that RFs, particularly of the IgG class, may participate in the pathogenesis of the renal injury in some patients with APSGN.
2284220 Lornoxicam in clinical practice. 1990 Three studies reported here have confirmed that lornoxicam is effective in osteoarthritis and the ideal dose appears to be 12 mg daily. Overall, lornoxicam appears to be a useful drug in the treatment of both osteo- and rheumatoid arthritis, from the data presently available.
2951347 Impairment, disability, and the ICIDH (International Classification of Impairments, Disabi 1987 This paper presents a further exploration of the conceptual scheme proposed in the International Classification of Impairments, Disabilities, and Handicaps which links underlying condition, impairment and disability. It examines the proposal that three general patterns of impairment profile might be expected depending on whether the underlying condition affects control (as in stroke or multiple sclerosis), mechanical performance (as in arthritis) or energy (as in cardiorespiratory conditions). Examination of patterns of functional limitation shows more resemblance between conditions in each of these groups than between the groups lending support to the proposal.
1765988 Serum concentrations of hyaluronan and proteoglycan in joint disease. Lack of association. 1991 Oct Circulating hyaluronan originating from the synovial membrane and circulating proteoglycan released from cartilage were determined by specific assays in patients with osteoarthritis (OA), rheumatoid arthritis (RA), reactive arthritis or juvenile chronic arthritis (JCA). Elevated hyaluronan concentrations were found in OA and RA, suggesting proliferation of the synovial membrane in both diseases. The proteoglycan concentrations were highest in OA and polyarticular JCA indicating increased turnover of cartilage matrix. The concentrations of the macromolecules did not correlate except in the group with JCA. Serum concentrations of hyaluronan and proteoglycan thus differ between disease groups and may reflect different aspects of the arthritic process.
3677374 Radioimmunoassay of tumor necrosis factor in serum. 1987 Nov We present a double-antibody radioimmunoassay for determination of the concentration of tumor necrosis factor (TNF) in serum. TNF in serum competes with a fixed amount of 125I-labeled TNF for the binding sites of specific rabbit antibodies. The bound TNF is precipitated with Sepharose-bound anti-rabbit IgG, then centrifuged, and the radioactivity of the pellets is counted. The detection limit of the assay is 7 ng/L (B0-3 SD). Bound radioactivity in the range of 10% to 90% of the B0 counts corresponds to TNF concentrations of 26 to 10,000 ng/L. Of 40 sera from healthy subjects, 21 (53%) contained TNF concentrations greater than 7 ng/L (range 8-40 ng/L). Some patients with parasitic or neoplastic disease and patients with septic shock had highly increased TNF values. Three of the 14 sera (21%) from patients with rheumatoid arthritis had TNF concentrations greater than 40 ng/L.
3659163 Prosthetic replacement of the condylar head for temporomandibular joint disease. 1987 Oct Temporomandibular joint replacement was performed in 8 adults who had intraarticular ankylosis, 6 who had end-stage osteoarthritis, and 12 who had rheumatoid arthritis. Three methods of replacement were used; an ulnar head prosthesis (8 patients), an interpositional implant (11 patients), and a Proplast-coated metallic prosthesis (7 patients). The mean age of the 26 patients (19 women and 7 men) at surgery was 38 years (range 17 to 58 years), and the mean follow-up was 36 months (range 3 to 84 months). Relief of pain was experienced by 23 patients, and maintenance or improvement of incisal opening was experienced by 21. Prosthetic replacement of the condylar head for end-stage disease is highly successful in the patients for whom it is indicated.
2892232 Analysis of restriction fragment length polymorphisms in rheumatic diseases. 1987 Aug Considerable evidence indicates that genes residing within the major histocompatibility complex (MHC) influence susceptibility to certain rheumatic diseases, such as ankylosing spondylitis (AS) and rheumatoid arthritis (RA). However, it has not yet been possible to precisely identify the gene(s) responsible for conferring enhanced susceptibility to these diseases. The availability of recombinant DNA technology should accelerate progress in obtaining this goal. A particularly promising method in this regard is restriction fragment length polymorphism (RFLP) analysis using appropriate class I and class II MHC gene probes. In preliminary studies, RFLPs have been identified for AS and RA which associate with susceptibility to the disease. Further studies using this approach should permit localization and precise identification of the disease susceptibility gene(s) for these diseases.
2649149 Slow-release artificial tear inserts in the treatment of dry eyes in patients with rheumat 1989 Feb Twenty-two patients with rheumatoid arthritis and moderate to severe bilateral keratoconjunctivitis sicca were treated with artificial tears and a soluble slow-release artificial tear insert in a crossover trial. While using the inserts all but two patients reported an improvement in their symptoms. All the patients showed an improvement in the degree of conjunctival and corneal staining while using the inserts (p = 0.0001 and 0.00001 respectively). Nineteen patients (86%) found the inserts an acceptable form of therapy and 14 (64%) preferred them to other treatment regimens. Placement of the insert was not a problem despite all the patients having rheumatoid changes in their hands resulting in varying degrees of deformity. Two patients experienced initial difficulties with placement, but these were quickly resolved.
2788742 Interleukin 2 and interleukin 2 inhibitors in human serum and synovial fluid. II. Mitogeni 1989 Jul Peripheral blood and synovial fluid (SF) mononuclear cells from 30 patients with rheumatoid arthritis (RA) were hyporesponsive to mitogenic stimulation with plant lectins and CD3 antibodies, due to depressed interleukin 2 (IL-2) production and IL-2 receptor upregulation. In contrast, in the seronegative arthritis patient group only SF mononuclear cells were hyporesponsive to mitogenic stimulation and there were no significant differences in IL-2 production or IL-2 receptor upregulation as compared with control subjects. No significant correlations were observed between IL-2 inhibitor levels and mitogenic responses, IL-2 production and IL-2 receptor upregulation on peripheral blood and SF mononuclear cells but an inverse correlation was noted between SF mitogenic responses and the expression of selected activation markers. We conclude that IL-2 abnormalities appear to be most pronounced in RA compared with other inflammatory arthritides and that these changes do not appear to be directly related to serum or SF IL-2 inhibitor levels.
2834817 Positive selection of antigen-specific B lymphocytes by means of immunomagnetic particles. 1988 Apr This paper presents a method for the isolation of highly enriched antigen-specific B lymphocytes from peripheral blood mononuclear cells (PBMC) by means of an immunomagnetic procedure. The method is illustrated by the isolation of B cells positive for rheumatoid factors (RF) from patients with rheumatoid arthritis and healthy blood donors. After Epstein-Barr virus transformation of isolated cells, more than 90% of the generated immunoglobulin-secreting cells produced RF in several experiments. Compared to the low frequency of B cells positive for RF in PBMC, this represents a 10(3)- to 10(4)-fold enrichment of antigen-specific B cells.
2671069 Penicillamine-induced bullous pemphigoid with pemphigus-like antibodies. 1989 Jun A rheumatoid arthritis case is described who developed bullous skin eruption with mucosal involvement after 3 years of treatment with penicillamine. Histologically, changes compatible with bullous pemphigoid were found. Direct immunofluorescence showed linear, as well as intercellular, deposits of IgG. By indirect immunofluorescence IgG antibodies reacting with the basal membrane zone, as well as the intercellular substance, were detected in the serum. We believe that the patient had bullous pemphigoid with pemphigus-like antibodies induced by penicillamine.
1888197 Evidence for a promoter of urate crystal formation in gouty synovial fluid. 1991 Aug The effect of serum and synovial fluid obtained from six healthy subjects and from 12 patients with gout, six with rheumatoid arthritis and 18 with calcium pyrophosphate dihydrate arthropathy (CPPD) on the rate of in vitro urate crystal formation was measured. Gouty and normal serum produced similar results. Gouty synovial fluids promoted urate crystal formation significantly more than did rheumatoid or CPPD fluids. The promotion of urate crystal formation by gouty synovial fluid was not due to native urate crystals nor to an effect on the level of urate supersaturation. The development of gout in some, but not other, hyperuricaemic subjects may relate to the presence of promoters (or relative lack of inhibitors) of urate crystal formation in the group who develop gout.
3496057 Gm allotypes and HLA in rheumatoid arthritis patients with circulating antibodies to nativ 1987 May HLA antigens and immunoglobulin heavy chain allotypes (Gm) were determined in 166 unrelated patients with rheumatoid arthritis (RA), 44 of whom had circulating antibodies to native type II collagen. Collagen antibody positive patients showed an association with HLA-DR3 and DR7 (68% compared with 39% of collagen antibody negative RA, p less than 0.005), and with the Gm phenotype, Gm(zafngb). This contrasted with the collagen antibody negative RA patients where there was an association with HLA-DR4 and, in DR4 positive disease only, with the Gm allotype, G1m(x). The Gm(zafngb) phenotype was found in 26% of DR3 or DR7 positive patients overall and only 9% of RA patients negative for these DR antigens (p less than 0.005), suggesting an interaction between HLA-DR3/7 and Gm(zafngb). The differing Gm associations for collagen antibody positive and negative RA provide further evidence for genetic heterogeneity in susceptibility to RA.
3260959 Thymocytotoxic antibodies in synovial fluid. 1988 Mar Synovial fluid (SF), obtained from patients with juvenile rheumatoid arthritis (JRA), osteochondritis, traumatic synovitis and septic arthritis were tested for the presence of thymocytotoxic activity. Such activity, directed against guinea pig thymocytes, was earlier demonstrated in human serum and shown to be mediated by IgM antibodies and a heat labile factor, most likely complement. The cytotoxic activity was demonstrated in all SFs tested, and was abolished by either one of the following procedures: depletion of IgM by use of anti-IgM-antibody coated protein A-Sepharose, or heating to 56 degrees C for 30 min. Activity was regained when samples inactivated by these two procedures were recombined. The cytotoxic SFs produced similar distortion of cell volume distribution of the target thymocytes as previously has been shown with human serum. The findings indicate that the two cytotoxic activities are identical. In most cases the IgM levels and the cytotoxic activity were lower in SF than in normal serum. Although the material does not permit correlation of cytotoxic activity with specific joint conditions, a high SF cytotoxicity was noted in two out of four patients with JRA. The demonstration of IgM-associated thymocytotoxic activity is of interest both in connection with earlier observations of various specific antibodies in SF and in connection with speculations regarding local immune regulatory activity in the joint.
12412745 Pattern of humoral reactivity to type II collagen in rheumatoid arthritis. 1989 Nov Humoral immunity directed against type II collagen (CII) is a common although not specific feature of rheumatoid arthritis (RA). We have shown that 10 to 15% of the sera either from RA patients (n = 88) or from healthy controls (n = 149) reacted with native human CII. Conversely, autoantibodies to the alpha-1 (II) chains were significantly more frequent in the RA group (26.1% versus 6.0%, P<0.001), suggestingthatdenaturedCII may bean autoantigenin RA. Thus, human CII was cleaved with cyanogen bromide (CB), and immunoblotting techniques were performed on 19 RA and 21 normal sera. Among the four major CB peptides, CB10 and CB11 were recognized by most of the sera tested without distinction between normal or RA sera. Inhibition experiments using an ELISA have shown that: (i) antibodies to the native CII molecule did not cross-react with those recognizing the CB peptides, and vice-versa; (ii) the binding of the sera to native CII was partially inhibited by pre-incubation with alpha-1 (II) chains, and vice-versa; (iii) pre-incubation of the sera with CB peptides partially blocked the binding to alpha-1 (II) chains, whereas pre-incubation of the sera with alpha-1 (II) chains totally inhibited the reactivity against CB peptides; and (iv) a substantial proportion of the epitopes recognized by anti-CII autoantibodies was neither species specific nor type specific. Taken together, these findings reveal the existence of several populations of anti-CII autoantibodies: some antibodies react exclusively with conformational determinants of the CII molecule, and others are directed towards linear structures of alpha-1 (II) chains.
3075463 Synovial localization of tumor necrosis factor in patients with rheumatoid arthritis. 1988 Aug Tissue localization of tumor necrosis factor (TNF alpha) was examined in synovial tissues from 10 patients with active rheumatoid arthritis (RA) and three osteoarthritis controls using both monoclonal and polyclonal antibodies to TNF alpha and immunoperoxidase technique. No prominent staining for TNF alpha was noted in any of the osteoarthritis non-inflammatory synovial samples; however, six out of 10 RA synovial tissues displayed strongly positive tissue distribution of TNF alpha epitopes particularly within synovial lining cells, and interstitial monocyte/macrophage cells within inflammatory infiltrates. The amounts of TNF alpha visualized within synovial lining cells appeared to parallel the extent of inflammatory cell collections within the rheumatoid synovial tissues examined. Similar studies using renal biopsy tissues from seven patients with Systemic Lupus Erythematosus (SLE) nephritis (including diffuse proliferative nephritis, nephrotic syndrome, focal glomerulonephritis, and membranous nephritis) showed no tissue localization of TNF alpha. These findings emphasize that a potent lymphokine (TNF alpha), which may be important in the underlying inflammatory process, appears to be localized and perhaps produced by synovial lining cells within active RA synovial tissues.
1933984 Amyloidosis of the oral cavity: report of five cases. 1991 May Five cases of amyloidosis involving structures in the oral cavity are reported. Three cases appeared to be secondary systemic amyloidosis, one case was the systemic form associated with multiple myeloma, and one case appeared to represent nodular or localized amyloidosis. All cases appeared in persons over 63 years of age, and the most common area of involvement was the tongue. The nature of so-called amyloid deposits in certain odontogenic tumors is discussed in light of recent knowledge of amelogenins and enamelins.
2517735 Clinical significance of combined antinuclear and anticytoplasmic antibodies detected by i 1989 Dec Anti-nuclear antibodies (ANA) combined with anti-cytoplasmic antibodies (ACA) in 0.6% (n = 43) of 7,121 consecutive patients referred for ANA screening were observed. Homogeneous/cytoplasmic was the most frequently combined ANA/ACA pattern among 6 different indirect immunofluorescent (IF) combinations. Distribution of diseases was similar in patients with ANA/ACA and those controls with ANA alone. However, the ANA/ACA results were often transitory, especially in systemic lupus erythromatosus (SLE). The appearance of transitory ANA/ACA combinations on serial ANA testing may be useful as a serologic marker for SLE.