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Marie-Christophe Boissier

Publications and source records attributed to Marie-Christophe Boissier.

28 records · Page 2Linked to original sources
PubMed2003

Recent data on the role for angiogenesis in rheumatoid arthritis.

Angiogenesis is central to the development and perpetuation of rheumatoid synovitis. Vascular endothelial growth factor (VEGF), the main mediator of angiogenesis, is found in the synovial fluid and serum of patients with rheumatoid arthritis (RA), and its expression is correlated with disease severity. Compelling evidence that VEGF is involved in synovitis has been obtained from experimental models of RA. In particular, VEGF inhibition by synthetic compounds (e.g. TNP-470) or by naturally occurring factors (e.g., the soluble VEGF receptor) produce therapeutic effects. Angiopoietin-1, a recently discovered growth factor specific for neovascularization, is expressed within the rheumatoid synovium and may be stimulated by TNF-alpha. Other compounds, including integrins, fibroblast growth factor, and proinflammatory cytokines contribute to joint angiogenesis and, therefore, to the development of rheumatoid synovitis. Assessing vascularity may prove useful for evaluating or even predicting bone destruction. Furthermore, inhibition of angiogenesis may prove useful as an adjunct to current anti-inflammatory treatments.

Arthritis, Rheumatoid↗
PubMed2002

Spinal epidural lipomatosis revealing endogenous Cushing's syndrome.

Spinal epidural lipomatosis is defined as accumulation of nonencapsulated fat within the spinal canal. It occurs chiefly in patients on long-term glucocorticoid therapy or in obese patients without any other detectable cause. We report the second case of spinal epidural lipomatosis revealing endogenous Cushing's syndrome.

Adenoma↗
PubMed2002

Clinical practice among rheumatologists: managing patients with rheumatoid arthritis.

The objective of this study was to review evaluations of current clinical practice among rheumatologists managing patients with rheumatoid arthritis. We reviewed articles retrieved through PubMed using the search terms 'rheumatoid arthritis', 'clinical practice', 'physician's practice patterns', and 'health service research'. We set the time limits at January 1990 and May 2001. Marked variability was found in initial tests, initial treatment, changes in clinical status by number of visits, second-line treatment prescription and monitoring, use of monitoring criteria, clinical outcomes by type of health care insurance, and management of a fictional case. The data were obtained by survey in some studies and by prospective collection in others. This literature review indicates a need for developing recommendations for the management of rheumatoid arthritis.

Arthritis, Rheumatoid↗
PubMed2002

[Pathogenesis of systemic scleroderma: immunological aspects].

Systemic sclerosis (SSc) is a connective tissue disorder that is characterized by excessive collagen synthesis by fibroblasts and by vascular hyperreactivity and obliteration phenomena. Excessive collagen production is the consequence of abnormal interactions between endothelial cells, fibroblasts and mononuclear cells. Immunological abnormalities are present very early in the development of SSc. Mononuclear cells, particularily macrophages and T lymphocytes play a prominent role in fibroblast activation and collagen synthesis through the cytokines they produce. Thus, lymphocytic infiltrates in the skin and in the lung are preferentially composed of CD8+ T lymphocytes, that produce important amounts of interleukin 4 (IL-4). The effects of IL-4 are added to these of transforming growth factor B (TGF-B) and connective tissue growth factor (CTGF) that stimulate collagen synthesis by fibroblasts. T lymphocytes produce important amounts of gamma interferon (INF-gamma) that is the best inhibitor of collagen synthesis by fibroblasts. However, the inhibitory effect of INF-gamma on collagen synthesis is diminished in SSc patients. Numerous autoantibodies can be evidenced in the serum of SSc patients. Three of them are specific for SSc and mutually exclusive: anti-centromere antibodies (Ab) in limited SSc, anti-Scl70 Ab in diffuse SSc and anti-RNA polymerase III Ab in diffuse SSc with renal involvement. These autoantibodies are good prognosis markers but their pathogenic role remains uncertain.

Autoantibodies↗
PubMedDate not supplied

Syngeneic fibroblasts transfected with a plasmid encoding interleukin-4 as non-viral vectors for anti-inflammatory gene therapy in collagen-induced arthritis.

BACKGROUND: No effective long-term treatment is available for rheumatoid arthritis. Recent advances in gene therapy and cell therapy have demonstrated efficiency in collagen-induced arthritis (CIA). Interleukin-4 (IL-4) is already known to be efficient in CIA in systemic injection or administered by gene therapy. This study was designed to evaluate the effect of a non-viral gene therapy of CIA, involving injection of syngeneic fibroblasts transfected with a plasmid encoding for IL-4. METHODS: Immortalised fibroblasts from DBA/1 mice (DBA/1/0 cells) were transfected with a plasmid expressing IL-4 cDNA (DBA/1/IL-4 cells). Xenogeneic fibroblasts from Chinese hamster ovary (CHO) transfected with a plasmid expressing IL-4 cDNA (CHO/IL-4) were studied also. The cells were engrafted in mice developing CIA by subcutaneous injection of 3 x 10(6) DBA/1/0 or DBA/1/IL-4 or CHO/IL-4 cells. RESULTS: Injection of DBA/1/IL-4 cells, on days 10 and 25 after immunisation, was associated with a significant and lasting improvement in the clinical and histological evidence of joint inflammation and destruction as compared with DBA/1/0 and CHO/IL-4 cells. DBA/1/IL-4 cell treatment decreased also the production of IgG2a antibody to CII and the proliferation of CIIB-specific nodal T cells. Later treatments (engraftments on days 23 and 35 after immunisation) exerted also an anti-inflammatory effect, as evaluated on clinical and histological signs of CIA. CONCLUSIONS: Taken together, these findings indicate that systemic administration of syngeneic cells transfected with an anti-inflammatory cytokine gene, namely IL-4, with a non-viral method is effective in CIA and may attenuate the cytokine imbalance seen in this disease.

Animals↗
PubMedDate not supplied

Gene therapy for rheumatoid arthritis.

Rheumatoid arthritis (RA) is a severe autoimmune systemic disease. Chronic synovial inflammation results in destruction of the joints. No conventional treatment is efficient in RA. Gene therapy of RA targets mainly the players of inflammation or articular destruction: TNF-alpha or IL-1 blocking agents (such as anti-TNF-alpha monoclonal antibodies, soluble TNF-alpha receptor, type II soluble receptor of IL-1, IL-1 receptor antagonist), antiinflammatory cytokines (such as IL-4, IL-10, IL-1), and growth factors. In this polyarticular disease, the vector expressing the therapeutic protein can be administered as a local (intra-articular injection) or a systemic treatment (extra-articular injection). All the main vectors have been used in experimental models, including the more recent lentivirus and adeno-associated virus. Ex vivo gene transfer was performed with synovial cells, fibroblasts, T cells, dendritic cells, and different cells from xenogeneic origin. In vivo gene therapy is simpler, although a less controlled method. Clinical trials in human RA have started with ex vivo retrovirus-expressing IL-1 receptor antagonists and have demonstrated the feasibility of the strategy of gene therapy. The best target remains to be determined and extensive research has to be conducted in preclinical studies.

Arthritis, Rheumatoid↗
PubMedDate not supplied

Osteoprotegerin and inflammation.

RANK, RANKL, and OPG have well established regulatory effects on bone metabolism. RANK is expressed at very high levels on osteoclastic precursors and on mature osteoclasts, and is required for differentiation and activation of the osteoclast. The ligand, RANKL binds to its receptor RANK to induce bone resorption. RANKL is a transmembrane protein expressed in various cells type and particularly on osteoblast and activated T cells. RANKL can be cleaved and the soluble form is active. Osteoprotegerin decoy receptor (OPG), a member of the TNF receptor family expressed by osteoblasts, strongly inhibits bone resorption by binding with high affinity to its ligand RANKL, thereby preventing RANKL from engaging its receptor RANK. This system is regulated by the calciotropic hormones. Conversely, the effects of RANKL, RANK, and OPG on inflammatory processes, most notably on the bone resorption associated with inflammation, remain to be defined. The RANK system seems to play a major role in modulating the immune system. Activated T cells express RANKL messenger RNA, and knock-out mice for RANKL acquire severe immunological abnormalities and osteopetrosis. RANKL secretion by activated T cells can induce osteoclastogenesis. These mechanisms are enhanced by cytokines such as TNF-alpha, IL-1, and IL-17, which promote both inflammation and bone resorption. Conversely, this system is blocked by OPG, IL-4, and IL-10, which inhibit both inflammation and osteoclastogenesis. These data may explain part of the abnormal phenomena in diseases such as rheumatoid arthritis characterized by both inflammation and destruction. Activated T cells within the rheumatoid synovium express RANKL. Synovial cells are capable of differentiating to osteoclast-like cells under some conditions, including culturing with M-CSF and RANKL. This suggests that the bone erosion seen in rheumatoid arthritis may result from RANKL/RANK system activation by activated T cells. This opens up the possibility that OPG may have therapeutic effects mediated by blockade of the RANKL/RANK system.

Animals↗