Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 2841121 | Susceptibility of cartilage collagens type II, IX, X, and XI to human synovial collagenase | 1988 Jul 15 | The action of purified rheumatoid synovial collagenase and human neutrophil elastase on the cartilage collagen types II, IX, X and XI was examined. At 25 degrees C, collagenase attacked type II and type X (45-kDa pepsin-solubilized) collagens to produce specific products reflecting one and at least two cleavages respectively. At 35 degrees C, collagenase completely degraded the type II collagen molecule to small peptides whereas a large fragment of the type X molecule was resistant to further degradation. In contrast, collagen type IX (native, intact and pepsin-solubilized type M) and collagen type XI were resistant to collagenase attack at both 25 degrees C and 35 degrees C even in the presence of excess enzyme. Mixtures of type II collagen with equimolar amounts of either type IX or XI did not affect the rate at which the former was degraded by collagenase at 25 degrees C. Purified neutrophil elastase, shown to be functionally active against soluble type III collagen, had no effect on collagen type II at 25 degrees C or 35 degrees C. At 25 degrees C collagen types IX (pepsin-solubilized type M) and XI were also resistant to elastase, but at 35 degrees C both were susceptible to degradation with type IX being reduced to very small peptides. Collagen type X (45-kDa pepsin-solubilized) was susceptible to elastase attack at 25 degrees C and 35 degrees C as judged by the production of specific products that corresponded closely with those produced by collagenase. Although synovial collagenase failed to degrade collagen types IX and XI, all the cartilage collagen species examined were degraded at 35 degrees C by conditioned culture medium from IL1-activated human articular chondrocytes. Thus chondrocytes have the potential to catabolise each cartilage collagen species, but the specificity and number of the chondrocyte-derived collagenase(s) has yet to be resolved. | |
| 2553583 | Unequal expression of complement C4A and C4B genes in rheumatoid synovial cells, human mon | 1989 Sep | C4A and C4B are closely related homologous complement proteins encoded in the class III region of major histocompatibility complex (MHC). The regulation of their expression is under genetic and hormonal control. In this study we investigated the synovial fluid plasma ratio of C4A and C4B of rheumatoid (RA) and osteoarthritis (OA) patients, and a predominance of the C4B gene expression by the synovial macrophages of RA patients was demonstrated. To clarify the tissue specificity of the expression of C4A and C4B genes, human monocytoid cell line U937 and hepatoma-derived HepG2 cells were studied. The gene expression of C4A and C4B were markedly different in these cells since a relative predominance of C4B mRNA in U937 cells and excess of that of C4A in HepG2 cells were detected. Recombinant interferon-gamma (IFN-gamma) up-regulated the expression of C4A gene in both cells, but had apparently no effect on the C4B gene. Our results demonstrate dissimilar expression patterns for the two human C4 genes, suggesting different tissue specific regulation of human C4A and C4B. | |
| 1649131 | Comparison of group I and II soluble phospholipases A2 activities on phagocytic functions | 1991 Apr | Soluble phospholipase A2 (PLA2) purified from rheumatoid synovial fluid (group II) and repurified Naja naja venom PLA2 (group I) were compared for their influence on phagocytic activity of human polymorphonuclear (PMN) and mononuclear (MO) phagocytes. Group II PLA2 reduced chemotaxis, adhesiveness, and intracellular bactericidal activity (ICBA) and induced release of muramidase from PMNs. Group I PLA2 suppressed chemotaxis, and enhanced ICBA but had no influence on other phagocytic functions. Group II PLA2 purified from synovial fluid or from placenta caused marked spontaneous superoxide generation followed by inhibition of phagocytosis-induced burst of energy. Group I Naja naja and porcine pancreatic PLA2 had no effect on superoxide generation. Group II but not group I PLA2 reduced markedly ICBA of monocytes. It may be concluded that human group II soluble PLA2, in concentrations comparable to those present in inflamed joints or in sera of patients with active arthritis or septic shock, causes spontaneous formation of the oxygen radical superoxide and release of lysosomal enzymes, and suppresses conventional phagocytic activities of PMNs and monocytes. Marked differences between group I and group II PLA2s may mean that these enzymes exert different influences on cell membrane. | |
| 1713188 | [Suppression of monocyte-macrophage activation by anti-CD4 therapy in patients with chroni | 1991 Apr | Monoclonal anti-CD4 antibodies have been introduced into the treatment of rheumatoid arthritis. A depletion of CD4+ T-cells down to 8% of the origin level (p less than 0.0001) followed the antibody application. Moreover, there was a significant reduction of blood monocytes to 30% (p less than 0.001). A reduced lymphocyte proliferation induced by antigens or mitogens was found in parallel. Prior to treatment, monocyte-macrophage activation in rheumatoid arthritis was signified by an increased expression of HLA-class II antigens and the CD14 antigen, and by an increased production of neopterin and interleukin-1. Anti-CD4 treatment resulted in a significant reduction of elevated levels of neopterin, beta 2-microglobulin in serum as well as IL-1 production in vitro. | |
| 3512423 | Duct-associated lymphoid tissue (DALT) of minor salivary glands and mucosal immunity. | 1986 Feb | Minor salivary glands (MSG) play a substantial role in the secretory immunoglobulin A (sIgA)-mediated immunity of the oral cavity. There are two possibilities for the induction of this immunity: (i) an explicitly local antigenic stimulus, or (ii) a remote stimulus as part of the so-called 'common mucosal immune system'. This communication is an attempt to consolidate available evidence in support of both possibilities and to address the former in detail. Although there is strong circumstantial evidence supporting the feasibility of MSG functioning as a part of the common mucosal immune system, direct experimental evidence is yet to emerge. On the other hand, there is increasing structural and physiological evidence in support of MSG serving as a local immunological organ. The purely local response is attributed to the presence of MSG duct-associated lymphoid tissue (DALT), which is comparable to gut- or bronchial-associated lymphoid tissue (GALT or BALT) in origin, tissue organization and function. DALT is accessible to oral antigens by retrograde passage through MSG ducts. Repeated topical antigenic challenging via the oral mucosa may result in the appearance of interacinar plasma cells carrying specific homologous antibodies in MSG. Gut or enteric priming of the same antigen, by passing the oral mucosa by gastric intubation, need not evoke a remote immune response in MSG. Since DALT is more likely to occur in healthy, young growing individuals, who are less likely to undergo bioptic examination of MSG, it has not yet been documented in humans. The physiologically induced DALT is apt to be confused with focal accumulations of lymphoid tissue in pathologically altered MSG, as a consequence of local and some systemic autoimmune diseases. An attempt is made to demarcaate healthy and pathological MSG on the basis of currently available clinical, serological, immunological and genetic evidence. | |
| 2533503 | Characterization of the IL-2-receptor on rheumatoid arthritis synovial fluid T cells. | 1989 Dec | We studied the hypoproliferative response of synovial fluid (SF) T cells in rheumatoid arthritis (RA) using a mitogenic monoclonal antibody (MoAb) specific for the T-cell antigen receptor-associated CD3 complex. RASF T cells are defective in their proliferative response and in the induction of the Tac (p55) component of the IL-2-receptor (IL-2-R) when stimulated with anti-CD3 monoclonal antibody (MoAb). However, fresh RASF T cells bear demonstrable IL-2-R in cross-linking experiments which are not seen in unstimulated peripheral blood (PB). These receptors are functional since RASF T cells proliferate in response to recombinant IL-2 (rIL-2) better than fresh PB T cells from either normal or RA patients. Scatchard analysis indicates increased (4-fold) numbers of high affinity IL-2-R on (phytohaemagglutinin) PHA-activated RASF T cells as compared with comparably activated RAPB T cells. Phorbol myristate acetate (PMA) induces Tac antigen expression in RASF but does not lead to proliferation. The hyporesponsiveness of RASF T cells does not appear to result from lack of IL-2-R, lack of IL-2-R inducibility, or proliferative potential. | |
| 2692947 | An assessment of tenoxicam, a nonsteroidal anti-inflammatory drug of long half-life, in pa | 1989 Dec | Fifty-eight patients, aged 48-87 years, with impaired renal function and mean initial creatinine clearance of 52.1 mls/min were recruited to a 12-week open study of tenoxicam 20 mg/day for osteoarthrosis or rheumatoid arthritis. Renal function was measured before and after a brief run-in period when patients discontinued all nonsteroidal anti-inflammatory drugs, taking paracetamol alone, prior to monthly monitoring thereafter. Fifty-four % of patients completed the study, the others being withdrawn from lack of efficacy (17%), adverse events (24%) or both (5%). During the run-in period the mean creatinine clearance of 28 patients completing the trial improved to 64.7 mls/min and then dropped to 57.9 mls/min during the course of 12 weeks treatment with tenoxicam. Serial analysis of haematological and biochemical safety parameters showed no drug-induced change of significance. Twenty-three% of patients felt worse and 45% better at the end of treatment. Seventeen patients withdrew because of adverse events. These were normally gastrointestinal and always unrelated to further deterioration in renal function. Tenoxicam, 20 mg/day, can be given safely for a period of at least three months in patients with mild or moderate renal impairment. | |
| 2688078 | Evaluation of the efficacy and safety of NSAIDs. A new methodological approach. | 1989 | When rheumatic patients were questioned concerning the most desired attributes for a nonsteroidal anti-inflammatory drug (NSAID), the majority of replies related to tolerability. For example; low frequency of gastrointestinal side-effects, safety in the elderly, a low frequency of renal side-effects and a superior anti-inflammatory effect than other drugs available, were all regarded as important NSAID properties. This focus on safety issues by patients is probably due to problems experienced in recent years with non-steroidals on the market. In particular, the withdrawal of benoxaprofen was of major concern for both doctors and patients, and this together with other events over the last few years has not really contributed to an improvement of the relationship between rheumatic patients and doctors. The NSAIDs which have experienced problems and resulted in withdrawal from the market are as follows: benoxaprofen (Coxigon), indoprofen (Flosin), indomethacin (Osmosin, Osmogit), isoxicam (Pacyl) and oxyphenbutazone (Tanderil). Additionally, there were restrictions on the usage of phenylbutazone. This has resulted in the major authorities requiring more data concerning safety issues. The following paper will discuss an overview of the methodology which is now used in the development of a NSAID, using data and procedures obtained from the evaluation of tenoxicam. | |
| 2158365 | Correlation between erythrocyte CR1 reduction and other blood proteinase markers in patien | 1990 Apr 15 | Erythrocyte CR1, a C3b/C4b-binding complement-regulatory protein, is sensitive to proteolysis in vitro. To test the hypothesis that in vivo erythrocyte CR1 reduction results from intravascular proteinase activities, we used enzyme-linked immunosorbent assays to measure gamma-crosslinked fibrin degradation products (D-dimers) as indicators of coagulation/fibrinolytic activity, and complexes of neutrophil elastase with alpha 1 proteinase inhibitor (E/A) as indicators of neutrophil enzyme release in malignant and inflammatory disorders. Erythrocyte CR1, measured by monoclonal anti-CR1 antibody binding, was inversely related to disease activity and blood proteinase markers. Levels of erythrocyte CR1 were significantly lower for patients with active versus remittent squamous and small cell lung cancers, Hodgkin's and diffuse large cell lymphomas, and acute myelogenous leukemias. In patients with active thoracic cancers, elevated D-dimer levels correlated with reduction of CR1. In patients with rheumatoid arthritis, CR1 reduction was correlated with elevated levels of elastase complexes. Our findings substantiate the relationship of acquired CR1 reduction to the activity of certain diseases and provide circumstantial support for the hypothesis that erythrocyte CR1 is lost to proteolysis in vivo. Although heritable differences in CR1 expression reduce the interpretability of single measurements of erythrocyte CR1 levels, disease-associated CR1 reduction may be a useful indicator of disorders with chronically increased blood proteinase activity. | |
| 2355392 | Uses and limitations in the demonstration of specific circulating immune complexes in pati | 1990 Jun | A micro-enzyme linked immunosorbent assay (micro-ELISA) has been evaluated as a diagnostic test to detect amoebic antigen in polyethylene glycol (PEG) precipitated circulating immune complexes (CIC) in sera from patients with amoebiasis. The immune complexes were captured on rabbit anti-amoebic IgG-coated wells of microtitration plates and the complexed antigen was detected by enzyme linked antihuman immunoglobulins. A titre of greater than 160 for the immune complexes was considered to be of clinical significance. The immunoassay detected amoebic, antigen-specific CIC in 35 (94.5%) of 37 patients with confirmed amoebic liver abscess. Twenty (55.5%) of 36 clinically suspected cases of amoebic liver abscess had amoebic antigen-specific CIC and responded favourably to anti-amoebic chemotherapy. Only two (20%) of 10 cases of non-dysenteric symptomatic intestinal amoebic infection had amoebic antigen-specific CIC. One (10%) of 10 patients with non-amoebic intestinal disorders also had amoebic antigen in CIC. However, none of 15 cases of non-amoebic hepatic disorders that included hydatid disease, metastatic adenocarcinoma, hepatocellular carcinoma, cholecystitis and choledocal cyst, 13 cases of rheumatoid arthritis and 25 apparently healthy subjects had amoebic antigen in CIC. The levels of the amoebic antigen-specific CIC did not correlate (p greater than 0.05) with either the number of abscess(es) or lobe(s) of the liver involved. However, the levels of antigen-specific CIC were higher (p less than 0.01) in patients with a liver size of more than 5 cm below the right costal margin. Antigen-specific CIC levels tended to decline or disappear during 3-6 months following completion of therapy.(ABSTRACT TRUNCATED AT 250 WORDS) | |
| 2510936 | Collagen-induced arthritis in mice. VI. Synovial cells from collagen arthritic mice activa | 1989 Dec | Synovial cells were extracted from normal and collagen-arthritic mice and investigated for lymphocyte-activating properties. In mixed cell culture, irradiated fibroblast-like synovial cells from DBA/1 LacJ arthritic mice stimulated a strong proliferative response in spleen cells from syngeneic normal mice, but not in cells from allogeneic DBA/2. B10.RIII, or BALB/c mice. This novel stimulus occurred in the absence of detectable Class II MHC antigen expression on the fibroblast-like synovial cell surface or increased autologous mixed lymphocyte reactions between DBA/1 LacJ spleen and lymph node cells. Irradiated synovial cells were also unable to present type II collagen to a collagen-specific T cell line and to stimulate proliferation. Addition of interferon-gamma or interleukin-1 failed to induce detectable surface Ia on the synovial fibroblasts or induce the capacity for antigen presentation in these cells. | |
| 2377941 | [A case of progressive systemic sclerosis associated with mutilans-type arthropathy and su | 1990 Feb | A patient who developed mutilans-type arthropathy, splenomegaly, leukopenia, leg ulcer and massive hydroxyapatite accumulation during the course of progressive systemic sclerosis (PSS) was reported. A 56-years-old female had suffered Raynaud's phenomenon since the beginning of her third decade. She developed multiple symmetrical arthritis and morning stiffness at the age of 29, and was treated with NSAIDs and low dose corticosteroids under the diagnosis of rheumatoid arthritis (RA) Because of dysphagia and diarrhea, she was admitted in Niigata-Kenritsu Senami Hospital in September, 1987. Physical and roentgenographic examinations revealed diffuse scleroderma, mutilans-type arthropathy, lung fibrosis, splenomegaly and right leg ulcer. Laboratory examinations showed leukopenia, high titer of anti-DNA antibody, positive anti-Scl-70 antibody and mild hypocomplementemia. These findings suggested that she had PSS and Felty's syndrome. Furthermore, massive subcutaneous and intraarticular hydroxyapatite accumulation were noticed. The leg ulcer and laboratory data gradually improved with the combination therapy of corticosteroids, D-penicillamine and plasmapheresis. Although it has been well recognized that PSS patients reveal frequently the articular lesions similar to these of RA, severe mutilans-type arthropathy seen in this case is extremely rare. The joint contracture might be induced by hydroxyapatite accumulation, of which the early diagnosis seems to be very important in long-standing PSS patients. | |
| 1664909 | Substrate specificity and activation mechanisms of collagenase from human rheumatoid synov | 1991 Dec | Substrate specificity studies of collagenase extracted from human rheumatoid synovium suggest that synovial pannus tissue overlying articular cartilage may not be particularly active in degradation of cartilage type II collagen, which, considering the poor inherent healing capacity of the articular hyaline cartilage, may exert a protective function against inadvertant tissue damage. Rheumatoid synovial tissue was also used to establish synovial fibroblast cell lines. Treatment of these cells in monolayer cultures with IL-1 leads to collagenase gene activation, increased collagenase production and an almost complete autoactivation of secreted collagenase. Interleukin-1 also activated stromelysin gene suggesting this as a possible mechanism effecting autoactivation. Latent human fibroblast and macrophage collagenase purified from culture medium were efficiently activated by phenylmercuric chloride but also by gold thioglucose, gold sodium thiomalate and HCIO. These new observations support the Cys73 switch activation mechanism. In contrast to neutrophil collagenase, the activation by gold(I) compounds and HCIO was associated with a change in the apparent molecular weight of the fibroblast procollagenase. In addition, gold(I) compounds rendered collagenase more susceptible to thermal denaturation. Thus the fibroblast-type interstitial collagenase, probably derived from fibroblast- and macrophage-like synoviocytes, seems to provide the predominant collagenolytic potential in human rheumatoid synovial tissue. Furthermore, the conditions in synovitis tissue may be such as to favor at least initial activation of collagenase synthesized and secreted in situ. | |
| 3638367 | Synthesis of complement components (C3, C2, B and C1-inhibitor) and lysozyme by human mono | 1986 Jul | The synthesis of C3, C2, factor B (B) C1-inhibitor and lysozyme has been studied in monocytes and macrophages isolated from the synovial fluids of patients with rheumatoid arthritis. Concentrations of all 5 proteins in culture supernatants were measured by the sandwich ELISA technique. Kinetic studies showed that only lysozyme and C3 could be detected in monocyte culture supernatants on the first day of culture, whereas C2, B and C1-inhibitor were not present until the third day. In contrast all 5 proteins could be detected in the supernatants of macrophage cultures on day 1. In both monocyte and macrophage cultures synthesis of lysozyme and C1-inhibitor continued throughout the culture period, whereas synthesis of C2, B and C3 appeared to be reduced after the fifth day in culture. Quantitative studies showed that the secretion rates of lysozyme (4,700 X 10(3) molecules/cell/hr) was similar in monocytes and macrophages. Synthesis rates for all 4 complement components in monocyte cultures were less than 0.2% of that for lysozyme. Although the synthetic rates were higher in macrophages, even then they constituted less than 2% of the rate for lysozyme. Synthetic rates for complement components, but not lysozyme, were increased by BSA-anti-BSA antigen-antibody complexes and reduced by serum-treated complexes. Although the functional activity of monocyte B was similar to that for serum, the activity of monocyte C2 was 5 times that of serum C2. As C42 formed with monocyte C2 had a half-life of 13.5 min at 30 degrees C, compared with 4.5 min for the enzyme formed with serum C2, it is probable that monocyte C2 is oxidized by the oxygen products of these cells. | |
| 3782795 | Anti-thyroglobulin anti-idiotypic antibodies in sera of patients with Hashimoto's thyroidi | 1986 Dec 15 | The objective of this study was to find naturally occurring anti-idiotypic (anti-Id) antibodies to anti-human thyroglobulin (anti-hTg) idiotype in sera of patients with autoimmune thyroid disease. Sera from patients with Hashimoto's thyroiditis (HT), Graves' disease (GD), rheumatoid arthritis (RA), and systemic lupus erythematosus (SLE) and sera from normal subjects were tested for the presence of anti-Id antibodies against mouse anti-hTg monoclonal antibodies (McAb) in indirect ELISA and in indirect solid-phase RIA. Microtitration plates were coated with six McAb, five of them directed against different epitopes on hTg molecule, and then incubated with patients' sera. The bound antibody was detected with either peroxidase or 125I-labeled anti-human IgG. The specific positive reaction was observed in four of 40 patients with HT, in two of 26 patients with GD, in seven of 58 patients with RA, and in none of 20 normal subjects. The detected binding was due to the presence of anti-hTg anti-Id antibodies and not to Tg-anti-Tg circulating immune complexes, as the positive sera did not contain hTg when resolved on SDS-PAGE, nor did they bind to all anti-hTg McAb tested. The binding was dose dependent, and titers of anti-Id antibodies varied from 1:243 to 1:2187. The binding could be inhibited up to 50% by hTg, but not by the thyroid microsomal antigen, indicating that some of those anti-Id might represent the internal image of the antigen. Serum from the patient 3403, showing the strongest reactivity against McAb A-3, was chosen for IgG purification and F(ab')2 fragment isolation. The 3403 F(ab')2 fragment, but not the Fc fragment, was found to react specifically with four mouse anti-hTg McAb but not with the control mouse IgG. Thus, the obtained results permit the conclusion that anti-hTg anti-Id antibodies could occur naturally during the course of thyroid autoimmune disorders. | |
| 3097788 | The specificity of human autoantibodies to IgG: the development of methodology for measuri | 1986 | A simple enzyme-linked immunosorbent assay (ELISA) inhibition test was devised to determine the separate specificities for rabbit IgG, Fc, and Fab fragments of IgM, IgG, and IgA antiglobulins in sera obtained from rheumatoid and normal individuals. Results of this test showed that most of the anti-rabbit IgG activity present in the three immunoglobulin (Ig) isotype preparations from a rheumatoid serum was specific for the Fc portion of whole IgG. Some anti-Fab activity was detectable in all three Ig isotypes examined, but this had much less avidity and/or specificity than the anti-Fc activity. In contrast, normal antiglobulins of M and G classes were mostly specific for the Fab region of rabbit Ig, although a small but measurable amount of Fc-specific antiglobulin was present and was of high relative avidity. The low normal serum IgA anti-IgG activity detected was essentially nonspecific. We conclude that normal antiglobulins differ from "rheumatoid factors" in their specificity and that this may relate to different roles in health and disease. | |
| 1777551 | Protection from gastrointestinal side-effects by azapropazone by its incorporation into a | 1991 Aug | Addition of glucose and sodium citrate to azapropazone, in proportions of 1:1:1 by weight reduced gastric mucosal damage in rats and there was a trend towards reduction in radiolabelled faecal red cell loss in human volunteers compared with that with azapropazone alone. The glucose and citrate did not affect the pharmacokinetics of azapropazone, or its therapeutic efficacy. While no difference was observed in endoscopic injury and in symptomatic gastrointestinal complaints in a multicentre comparison in rheumatic patients, a striking reduction in symptoms was observed in those patients with a history of severe gastrointestinal intolerance to non-steroidal anti-inflammatory drugs. | |
| 2961487 | Synovial fluid mononuclear cells exhibit a spontaneous HLA-DR driven proliferative respons | 1987 Oct | We have tested the hypothesis that the spontaneous proliferation of synovial fluid mononuclear cells (SFMC) observed during in vitro culture is due to a mechanism analogous to the autologous mixed lymphocyte reaction (AMLR). Thus by observing the effect of addition of cyclosporin A, monoclonal anti-HLA-DR antibody, and recombinant interleukin 2 (rIL-2) on the spontaneous proliferation of SFMC from patients with rheumatoid arthritis (RA) and a wide range of seronegative spondyloarthritides (SN), we have demonstrated that this phenomenon is: (i) a T cell response, (ii) inhibited by the addition of cyclosporin A or monoclonal anti-HLA-DR antibody, (iii) enhanced by the addition of rIL-2 and (iv) the rIL-2 enhancement of the spontaneous proliferation is inhibited by a monoclonal anti-HLA-DR antibody. These observations suggest that the spontaneous proliferation of SFMC is at least in part an HLA-DR driven, IL-2 dependent event analogous to the AMLR, and support the concept derived from immunohistological studies of an important role for an antigen-presenting cell/T cell interaction occurring in the synovial membrane in inflammatory joint diseases such as RA. | |
| 3258386 | Deforming arthropathy of the hands in systemic lupus erythematosus. | 1988 Jan | Forty-one of 858 patients with systemic lupus erythematosus (SLE) developed clinical deformity of their hands. This deformity was clinically and radiologically different from that found in 40 patients with classical or definite rheumatoid arthritis (RA), and tended to appear early in the course of disease. Characteristics of this arthropathy included nonerosive carpal collapse; exceptional erosion of the styloid processes; Z deformity of the thumb; nonerosive ulnar deviation and subluxation of MCP joints; parametacarpophalangeal joint hook formation; scant and asymmetric joint erosions; and swan neck deformity of the fingers. Most of these changes seemed to be due to involvement of the ligaments rather than to the destructive effect of synovitis. Patients with SLE with deforming arthropathy had a higher frequency of rheumatoid factor positivity, sicca symptoms and antibodies to native DNA, whereas they had lower incidence of facial rash and photosensitivity than did those without. Other manifestations did not differ. We propose that most patients with SLE with deforming arthropathy belong to a subset of SLE rather than representing the coexistence of SLE and RA. | |
| 2165607 | Generation of collagenase-resistant collagen by site-directed mutagenesis of murine pro al | 1990 Aug | Collagenase (matrix metalloproteinase 1) cleaves type I, II, and III collagen helices at a specific site between Gly-Ile or Gly-Leu bonds (residues 775 and 776, P1-P1'). To understand the mechanism of collagen processing, mutations around the cleavage site have been introduced into the cloned murine pro alpha 1(I) collagen (Col1a1) gene. These mutant constructs have been transfected into homozygous Mov13 fibroblasts that do not express the endogenous Col1a1 gene due to a retroviral insertion. Secreted triple-helical type I collagens containing substitutions of Pro for Ile (position 776) (P1') were not cleaved by human rheumatoid synovial collagenase, whereas those containing substitutions of Met for Ile (position 776) were cleaved. Type I collagens containing double substitutions of Pro for Gln-774 (P2) and Ala-777 (P2') were not cleaved regardless of whether they contained the wild-type residue Ile at position 776 or the substitution of Met for Ile at position 776. The wild-type alpha 2(I) chains derived from the endogenous Col1a2 gene were also resistant to enzyme digestion when they were complexed with the mutant alpha 1(I) chains, indicating that the presence of normal alpha 1(I) sequences is critical for cleavage of the alpha 2(I) chains in the type I heterotrimer. |