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1.
Osteoarthritis Cartilage ; 26(8): 1110-1117, 2018 08.
Article in English | MEDLINE | ID: mdl-29803826

ABSTRACT

OBJECTIVES: The chondrocytes' pericellular matrix acts as a mechanosensor by sequestering growth factors that are bound to heparan sulfate (HS) proteoglycans. Heparanase is the sole mammalian enzyme with HS degrading endoglycosidase activity. Here, we aimed to ascertain whether heparanase plays a role in modulating the anabolic or catabolic responses of human articular chondrocytes. METHODS: Primary chondrocytes were incubated with pro-heparanase and catabolic and anabolic gene expression was analyzed by quantitative polymerase chain reaction (PCR). MMP13 enzymatic activity in the culture medium was measured with a specific fluorescent assay. Extracellular regulated kinase (ERK) phosphorylation was evaluated by Western blot. Human osteoarthritis (OA) cartilage was assessed for heparanase expression by reverse-transcriptase PCR, by Western blot and by a heparanase enzymatic activity assay. RESULTS: Cultured chondrocytes rapidly associated with and activated pro-heparanase. Heparanase induced the catabolic genes MMP13 and ADAMTS4 and the secretion of active MMP13, and down-regulated the anabolic genes ACAN and COL2A1. PG545, a HS-mimetic, inhibited the effects of heparanase. Heparanase expression and enzymatic activity were demonstrated in adult human osteoarthritic cartilage. Heparanase induced ERK phosphorylation in cultured chondrocytes and this could be inhibited by PG545, by fibroblast growth factor 2 (FGF2) neutralizing antibodies and by a FGF-receptor inhibitor. CONCLUSIONS: Heparanase is active in osteoarthritic cartilage and induces catabolic responses in primary human chondrocytes. This response is due, at least in part, to the release of soluble growth factors such as FGF2.


Subject(s)
Cartilage, Articular/enzymology , Chondrocytes/enzymology , Glucuronidase/metabolism , Osteoarthritis/enzymology , Adult , Blotting, Western , Cartilage, Articular/cytology , Cartilage, Articular/metabolism , Cartilage, Articular/pathology , Chondrocytes/metabolism , Humans , Matrix Metalloproteinase 13/metabolism , Osteoarthritis/metabolism , Osteoarthritis/pathology , Real-Time Polymerase Chain Reaction , Reverse Transcriptase Polymerase Chain Reaction
3.
Vaccine ; 29(8): 1643-8, 2011 Feb 11.
Article in English | MEDLINE | ID: mdl-21211590

ABSTRACT

OBJECTIVES: Yearly vaccination against influenza is currently recommended to patients with rheumatoid Arthritis (RA). Antibody and cell-mediated responses are both involved in the defense against influenza. Humoral responses to influenza vaccine are impaired in RA patients treated with rituximab (RTX). The objectives of this study were to comparatively assess cell mediated and humoral responses to influenza vaccination in RA patients with or without RTX-induced CD20 B-cell depletion. METHODS: Trivalent influenza subunit vaccine was administered to 46 RA patients and to 16 healthy controls. The RA group included 29 patients treated by RTX and 17 on conventional disease-modifying anti-rheumatic drugs (DMARDs), mostly methotrexate. Peripheral blood mononuclear cells and sera were obtained immediately before and 4-6 weeks after vaccination. Cell-mediated response to influenza antigens was evaluated by flow cytometry for activated CD4 T-cells. Humoral response was evaluated by haemagglutination inhibition assay. RESULTS: Cellular response: Cell-mediated responses were comparable in RTX-treated vs. DMARDs-treated patients. The recall postvaccination CD4+ cellular response was similar in RA patients and healthy controls. A positive correlation was found between CD19+ cell count on the day of vaccination and cellular response in RTX-treated RA patients. Humoral response: The antibody response rate was significantly impaired in the RTX group: being 26.4%, 68.4% and 47.1% in RTX-treated, DMARDs-treated and controls, respectively. CONCLUSION: Cellular immunity to influenza vaccination in RTX-treated patients was similar to DMARDs-treated patients and healthy controls, while humoral immunity was severely impaired. The preservation of cellular immunity may explain the relatively low rate of infection among B-cell depleted patients.


Subject(s)
Antibodies, Monoclonal, Murine-Derived/therapeutic use , Antirheumatic Agents/therapeutic use , Arthritis, Rheumatoid/immunology , Immunity, Cellular , Influenza Vaccines/immunology , Adult , Aged , Antibodies, Viral/blood , Antibody Formation/immunology , Arthritis, Rheumatoid/drug therapy , B-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/immunology , Case-Control Studies , Female , Hemagglutination Inhibition Tests , Humans , Immunity, Humoral , Influenza Vaccines/administration & dosage , Influenza, Human/immunology , Influenza, Human/prevention & control , Leukocytes, Mononuclear/immunology , Male , Methotrexate/therapeutic use , Middle Aged , Rituximab
4.
Int J Tuberc Lung Dis ; 13(11): 1427-32, 2009 Nov.
Article in English | MEDLINE | ID: mdl-19861018

ABSTRACT

OBJECTIVE: To compare the performance of QuantiFERON-TB Gold (QFT-G) with that of the tuberculin skin test (TST) in detecting latent tuberculosis (LTBI) among patients with rheumatoid arthritis (RA). PATIENTS AND METHODS: A total of 35 RA patients and 15 healthy controls underwent TST, QFT-G assays and chest X-ray and filled out a questionnaire on predisposing conditions for TB disease. Serum interferon gamma (IFN-gamma) levels were tested by an enzyme-linked immunosorbent assay. RESULTS: Forty-five per cent of RA patients had a TST > 5 mm vs. 26% in healthy controls. In the RA patients, QFT-G was positive in 11.4%, negative in 60% and indeterminate in 28.6%. The overall agreement between TST and QFT-G was significantly lower in the RA population than in controls (56% vs. 84%). No correlation was found between the use of prednisone, methotrexate and QFT-G results or agreement between TST and QFT-G. A low IFN-gamma level (<4 pg/ml) was found in 51.5% of the RA patients. No correlation was found between serum IFN-gamma levels and QFT-G results. CONCLUSION: The clinical significance of negative QFT-G in TST-positive patients with low TB risk remains to be assessed. The high rate of indeterminate results questions the clinical utility of QFT-G in the diagnosis of LTBI in RA patients.


Subject(s)
Arthritis, Rheumatoid/complications , Enzyme-Linked Immunosorbent Assay , Interferon-gamma/blood , Latent Tuberculosis/diagnosis , Mycobacterium/immunology , Reagent Kits, Diagnostic , Tuberculin Test , Antirheumatic Agents/therapeutic use , Arthritis, Rheumatoid/drug therapy , Biomarkers/blood , Case-Control Studies , Female , Humans , Latent Tuberculosis/diagnostic imaging , Latent Tuberculosis/microbiology , Male , Methotrexate/therapeutic use , Middle Aged , Pilot Projects , Predictive Value of Tests , Prednisone/therapeutic use , Radiography , Surveys and Questionnaires
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