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Marie-Christophe Boissier

Publications and source records attributed to Marie-Christophe Boissier.

At least 19 recordsLinked to original sources
PubMed2005

Role for innate immunity in rheumatoid arthritis.

Innate immunity is the first line of defense against pathogenic microorganisms (bacteria, viruses, fungi, and parasites). After a long period of neglect, innate immunity is again recognized as a key mechanism not only in preventing invasion of the body by microorganisms, but also in contributing to the pathogenesis of autoimmune and inflammatory diseases by deviating the immune response or promoting the emergence of a regulatory response. The many factors involved in innate immunity often act in parallel or in alternation to generate adaptive immune responses. Innate immune responses are specific for groups of molecules or macromolecules found in components of microorganisms, usually the cell wall. The cellular and protein effectors of innate immunity are found in the rheumatoid synovium, and an increasing body of evidence indicates that they are directly involved in joint inflammation and in destruction of the joint cartilage and bone. In addition, they may have regulatory effects on inflammation and immunity. Whether innate immune mechanisms are causes or consequences of inflammation, and whether they regulate or amplify adaptive immune responses, they constitute a target of choice for new antiinflammatory and immunoregulating treatment strategies.

Animals↗
PubMed2004

IgG reactivity with a 100-kDa tissue and endothelial cell antigen identified as topoisomerase 1 distinguishes between limited and diffuse systemic sclerosis patients.

We have analyzed antibody (Ab) reactivities of patients with limited systemic sclerosis (SSc) and anti-centromere Ab, patients with diffuse SSc and anti-topoisomerase 1 (anti-topo 1) Ab, patients with diffuse SSc without anti-topo 1 or anti-centromere Ab and age- and gender-matched healthy controls with normal human tissue and endothelial cell (EC) antigens. IgG reactivities with tissue antigens differed significantly between patients with anti-topo 1 Ab and patients with anti-centromere Ab. One 100-kDa band identified as topoisomerase 1 in macrovascular and microvascular EC extracts was recognized by IgG from patients with anti-topo 1 Ab and 50% of patients without specific Ab. IgG from patients with limited SSc and anti-centromere Ab, but not those of other patients or controls specifically recognized a 80-kDa band only in microvascular EC. Our results indicate that Ab from patients with limited or diffuse SSc with or without anti-topo 1 Ab exhibit specific and mutually exclusive reactivity patterns.

Autoantibodies↗
PubMed2004

Do primary care physicians have a place in the management of rheumatoid arthritis?

OBJECTIVE: Few recommendations have been issued about the management of rheumatoid arthritis (RA), which varies widely across physicians. The primary care physician (PCP) plays a unique role as the first physician to evaluate the patient. The objective of this study was to evaluate the place of PCPs in the management of RA. METHODS: Medline was searched for articles reporting management of rheumatoid arthritis in primary care practice. RESULTS: Currently, the goal of initiating a disease modifying anti-rheumatic drug (DMARD) early is unrealistic for numerous patients. Agreement between PCPs and rheumatologists about the diagnosis of RA is only passable, but PCPs tend to overdiagnose RA. Median time from symptom onset to second-line treatment was 19 months and the best predictive factor for a longer lag time before DMARD prescription was the time from symptom onset to the first rheumatologist visit. Moreover, DMARDs are only rarely prescribed by PCPs. Some data suggest that the impact of rheumatologists care is positive on outcomes but it has to be confirmed by longitudinal, randomized studies, with valid outcomes and diagnosis criteria. Recognition of the need for timely referral is an important goal in the teaching of students and generalists. Moreover, the nature of management differences between rheumatologists and PCPs has to be explored. We should also think how to create a better coordination. This starts by knowing what are the needs of the PCP (e.g. education, access to phone advice or rapid consultation) and by defining common plan if the care should be shared. CONCLUSION: Several healthcare professionals, among whom the PCP plays a pivotal role, should share the management of RA. PCPs and rheumatologists should be encouraged to work together on optimizing the management of patients with RA.

Arthritis, Rheumatoid↗
PubMed2004

Rheumatoid arthritis: direct and indirect costs.

Rheumatoid arthritis (RA) causes disability, deformities, progressive radiological joint damage often with a need for joint replacement surgery, premature death, and alterations in quality of life. The economic burden created by RA is enormous. Direct costs per patient have been estimated at 1812-11,792 Euro annually and indirect costs at 1260-37,994 Euro annually. These mean values are approximations, as variations occur across countries, healthcare system organizations, and geographic locations. Direct costs account for one-fourth to slightly over a half of the total cost. Costs associated with inpatient care contribute up to 75% of direct costs, as compared to only about 20% for medications, although wide variations occur in costs related to drug monitoring and side-effect management. Physician visits account for about 20% of direct costs. As compared to indirect health costs for individuals from the general population, those for RA patients are increasing at a rapid rate. Indirect costs account for 80% of the excess cost related to RA. Cost estimates may change over time and show huge variations across individuals, with a small minority of patients accounting for most of the costs. Disability as measured by the Health Assessment Questionnaire (HAQ) has a major impact on costs. Early effective treatment may not only postpone and slow disease progression, thereby improving quality of life, but also decrease costs by preserving productivity and reducing the need for surgery, admission to acute-care and extended-care hospitals, and social service utilization. Data are beginning to accumulate on the excess costs associated with biotherapies and other new second-line drugs. They indicate acceptable excess costs relative to the additional medical benefits and to the cost-effectiveness of other healthcare programs. Nevertheless, the threshold that defines an acceptable excess cost is arbitrary and varies with local economic conditions.

Arthritis, Rheumatoid↗
PubMed2004

Role for osteoprotegerin in rheumatoid inflammation.

Osteoprotegerin (OPG), a member of the TNF-receptor family expressed by osteoblasts, has documented effects on the regulation of bone metabolism. OPG inhibits bone resorption and binds with strong affinity to its ligand RANKL, thereby preventing RANKL from binding to its receptor RANK. This system is regulated by calcium-modifying hormones. OPG may also be pivotal in modulating the immune system. RANKL-deficient mice exhibit both severe immunological abnormalities and osteopetrosis, and activated T cells express RANKL mRNA. RANKL secretion by activated T cells may induce osteoclastogenesis via a mechanism enhanced by several cytokines (TNF-alpha, IL-1, and IL-17) that promote both inflammation and bone resorption. Conversely, this mechanism is inhibited by OPG, IL-4, and IL-10, which have antiinflammatory effects and inhibit osteoclast formation. Activated T cells in the rheumatoid synovium express RANKL. Synoviocytes can differentiate to osteoclast-like cells under specific conditions, particularly when they are cultured with M-CSF and RANKL. Thus, the bony erosions seen in RA may result from RANKL/RANK system activation by activated T cells. This raises the possibility that OPG therapy to block this mechanism might prove beneficial in patients with RA.

Animals↗
PubMed2004

Immune response against gene therapy vectors: influence of synovial fluid on adeno-associated virus mediated gene transfer to chondrocytes.

Intraarticular gene transfer with adeno-associated virus (AAV) vectors may allow efficient therapeutic transgene expression within the joint. In an effort to understand potential obstacles (particularly immunity against AAV vectors) to intraarticular gene therapy better, our objective was to determine whether synovial fluid (SF) influenced AAV-mediated gene transfer to chondrocytes. SF and sera from 21 patients with joint diseases were collected. Neutralizing activity against AAV/interleukin-4 (IL-4) was determined by assessing the ability of SF or serum to inhibit AAV/IL-4 transduction to the C20A4 chondrocytes. IgGs were purified from SF by salt-dependent chromatography. Anti-AAV IgG levels were determined by ELISA in the SF. SF and sera from all the patients inhibited AAV-mediated gene transfer to chondrocytes. Six SF out of 21 exerted a stronger inhibition. Serum from healthy patients were also inhibitory. Purified IgGs from SF exhibited inhibition patterns similar to those seen with whole SF. Anti-AAV IgG were found in SF from 13 patients out of 18. Moreover, in the SF, anti-AAV IgG level was correlated with the neutralizing activity (p < 0.001, r = 0.716). A correlation was observed between levels of inhibition by the SF and serum (P < 0.0001, r = 0.813). Inhibition of AAV/IL-4 infection of C20A4 cells by SF and sera was abolished by increasing the number of AAV/IL-4 particles. SF from patients with joint disease consistently inhibited AAV infection of chondrocytes in vitro. This effect was ascribable to IgG, most probably directed against AAV. In the future, these data may be useful for tailoring intraarticular AAV-mediated gene therapy to individual patients.

Adult↗
PubMed2004

Interleukin-4 cellular gene therapy and osteoprotegerin decrease inflammation-associated bone resorption in collagen-induced arthritis.

To evaluate the respective action of IL-4, an anti-inflammatory cytokine, and OPG, an inhibitor of bone resorption, on the inflammatory process and the associated bone resorption in collagen-induced arthritis (CIA). After CIA induction, DBA/1 mice were treated with OPG or with IL-4 DBA/1 transfected fibroblasts or both OPG + IL-4. CIA significantly improved in IL-4 groups. OPG had no effect on arthritis clinical scores but histologic scores were reduced in OPG, IL-4, and OPG + IL-4 groups vs. nontreated CIA mice. OPG increased significantly BMD and decreased by 45% D-pyridinolin levels. Moreover association of IL-4 and OPG exerted an additive effect of BMD and resorption marker (-68%). Production of IFN-gamma in the supernatants of spleen cells was reduced in IL-4 treated mice. OPG had a moderate effect on IFN-gamma, but potentiated the inhibitory effect of IL-4. OPG and IL-4 prevent bone loss in CIA-mice model and could have additive effects on IFN-gamma secretion.

Animals↗
PubMed2004

Gene therapy of collagen-induced arthritis by electrotransfer of human tumor necrosis factor-alpha soluble receptor I variants.

Electrotransfer is a simple and efficient strategy of nonviral gene delivery. We have used this method to deliver plasmids encoding three human tumor necrosis factor-alpha soluble receptor I variants (hTNFR-Is) a monomeric hTNFR-Is, a chimeric hTNFR-Is/mIgG1, and a dimeric (hTNFR-Is)(2) form. Electrotransfer parameters were studied and because anti-TNF strategies have proven efficient for the treatment of rheumatoid arthritis in clinics, we used a collagen-induced arthritis (CIA) mouse model to assess the efficacy of our constructs in the treatment of the disease. All proteins were proven bioactive, both in vitro and ex vivo. Plasmid intramuscular electrotransfer in mice resulted in a local expression of the three variants for at least 6 months; systemic expression lasted also more than 6 months for the hTNFR-Is/mIgG1 form, while it was shorter for the two other forms. This expression was plasmid dose-dependent. Electrotransfer of 50 microg of hTNFR-Is/mIgG1 at the onset of a CIA induced a clear-cut decrease in both clinical and histologic signs of the disease; the dimeric form also showed some efficacy. Moreover, the long-lasting protective effect was observed for more than 5 weeks. Comparison of this electrotransfer approach with repeated recombinant protein (etanercept) injections highlighted the potential practical interest of gene therapy approach for CIA, which leads to sustained therapeutic effect after single treatment. These results show that electrotransfer may be a useful method to deliver cytokine or anticytokine therapy in rheumatoid arthritis and also illustrate the potentiality of plasmid intramuscular electrotransfer for the rapid screening and assessment of different variant forms of secreted proteins.

Animals↗
PubMed2003

Efficacy of interleukin-10 gene electrotransfer into skeletal muscle in mice with collagen-induced arthritis.

BACKGROUND: Gene therapy is very promising in the treatment of rheumatoid arthritis (RA). Electrotransfer is a recent method reported to enhance in vivo intramuscular DNA transfection. Interleukin-10 (IL-10) has antiinflammatory effects in RA and in collagen-induced arthritis (CIA), a murine model of RA. In order to improve our strategy of gene therapy, we used electrotransfer to enhance penetration into skeletal muscle with CIA of plasmids encoding IL-10. METHODS: CIA was induced in DBA/1 mice by immunization with bovine type II collagen. Injection into the tibial cranial muscle of low-dose (200 ng) pCOR plasmid encoding murine IL-10 (pCOR-CMV-mIL-10) was immediately followed by application of square-wave electric pulses (8 pulses of 200V/cm, 20 ms duration at 2 Hz). Control groups received empty plasmid or saline before electrotransfer. RESULTS: When electrotransfer was performed twice on days 10 and 25 postimmunization, CIA was significantly delayed (P < 0.05) and attenuated (P < 0.001) in groups treated by electrotransfer or pCOR-CMV-mIL-10 plasmid vs. control groups. When electrotransfer of pCOR-CMV-mIL-10 plasmid was performed on days 25 and 40 postimmunization, at disease onset, the clinical severity of CIA was reduced (P < 0.05). All groups which had been electrotransferred early or late by pCOR-CMV-mIL-10 plasmid showed suppression of histological signs of arthritis. CONCLUSIONS: Taken together, these data indicate that administration of an antiinflammatory plasmid-born gene by electrotransfer of naked DNA is effective in vivo in an arthritis model.

Animals↗
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↗