Biomedical subjects
Publications and source records attributed to M C Boissier.
The authors report the case of an eight-year-old boy who developed erythroderma under carbamazepine. Other findings were enlarged lymph nodes, slight hepatic cytolysis, leuconeutropenia and decrease in the three classes of immunoglobulins. The immunosuppressive effect of the drug is recalled. Respective responsibility of immunosuppression and allergy is discussed.
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), anti-inflammatory cytokines (such as IL-4, IL-10, IL-1), 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 has been used in experimental models, including the more recent lentivirus and adeno-associated virus. Ex vivo gene transfer was done with synovial cells, fibroblasts, T cells, dendritic cells, and different cells from xenogenic origin. In vivo gene therapy is simpler, although less controlled method. Clinical trials in human RA has started with ex vivo retrovirus expressing IL-1 receptor antagonist and have demonstrated the feasibility of the strategy of gene therapy. The best target remains to be determined and extensive researches have to be conducted in pre-clinical studies.
OBJECTIVE: To describe the practices of rheumatologists in France regarding the initial management of early rheumatoid arthritis (RA) and to estimate the associated costs. METHODS: A questionnaire on the diagnosis and treatment of early RA was sent to the 2485 practicing rheumatologists in France. The results of the 917 completed questionnaires (37% response rate) were analyzed, and initial investigation and treatment costs, including the first month of treatment, were calculated from a socio-economic perspective. RESULTS: For the RA diagnosis, more than 80% of the respondents recommended the erythrocyte sedimentation rate, C-reactive protein, complete blood count, rheumatoid factor, antinuclear antibody and wrist radiographs. In 40% and 60% of the cases, antikeratin antibody, liver enzymes, serum creatine, serum protein electrophoresis and radiographs (chest, foot and knee) were advocated. Initial drugs administered were non-steroidal antiinflammatory agents (88%), analgesics (76%), disease modifying anti-rheutmatic drugs (74% with methotrexate in 46% of cases, followed by hydroxychloroquine [13%], sulfasalazine [8%], leflunomide [7%], intramuscular gold therapy [6%]), and glucocorticoids (21%). Rehabilitation was recommended by 51% of the respondents. The median cost for this initial management was 273 euros (mean 301 euros, range 49-1,336 euros). CONCLUSION: Marked variations occur among French rheumatologists in the initial management of early RA. These data may be helpful in identifying obstacles to physician compliance with recommendations regarding everyday clinical practice and to set up more a specific evaluative study.
OBJECTIVE: To describe the practices of rheumatologists in France for managing a flare in a patient being treated for long-standing rheumatoid arthritis (RA) and to estimate the corresponding costs. METHODS: A survey questionnaire was sent to the 2485 practicing rheumatologists in France; 917 completed questionnaires were returned (37% response rate). The questionnaire collected information on the respondents and on their recommendations for managing a fictional patient with a 10-year history of RA in flare, with a recent episode of neck pain, despite prednisone and methotrexate therapy. Investigational and treatment (first month) costs were estimated from the perspective of society in 2001 Euros. RESULTS: Over 80% of the respondents recommended measuring laboratory inflammation parameters, complete blood cell counts, liver enzymes, serum creatinine, and radiographs (hands, anteroposterior cervical spine view, wrists, knees); 50-70% recommended additional cervical spine incidences, elbow and chest radiographs, and bone absorptiometry. Adding anti-TNF therapy (24%) or another DMARD (10%), increasing the methotrexate dosage (24%), and substituting leflunomide for methotrexate were the main recommended treatments. Most respondents suggested continuing the glucocorticoid in the same dosage (61%) or a higher dosage (36%). Analgesics and non-steroidal anti-inflammatory drugs were recommended by 65% and 41% of respondents and rehabilitation therapy by 83%. The median cost was 500 Euro (mean 1105 Euro; range 80-4089 Euro). CONCLUSION: We found a high level of agreement among French rheumatologists regarding the evaluation of established RA. Marked variations in recommended treatments were observed and translated into major cost differences.
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Counteracting the effect of autoimmunity can be achieved by elimination or inactivation of autoreactive T cells. We have focused on two approaches targeting on autoaggressive T cells in the model of collagen-induced arthritis (CIA) in mice. First, type II collagen (CII) primed DBA/1 mice were treated with various monoclonal antibodies (mAb) specific for the beta chains of the T cell receptor (TCR) using a protocol resulting in a long-term elimination of the target T cells. Indeed, CIA could be suppressed by injection of anti-V beta 8.1, 2 mAb and down-regulated by that of anti-V beta 2 and/or anti-V beta 5, presumably by deleting pathogenic T cell clones. In contrast, treatment with either anti-V beta 6 or anti-V beta 11 mAb did not alter CIA. Second, we generated CII-specific T cell hybrid clones that recognize the antigenic peptides in association with Kq and IA(q) molecules respectively for CD8+ and CD4+ cells. Vaccination with the irradiated hybrid clones, 3 weeks prior to immunization, was effective in preventing the development of arthritis. Furthermore, this suppression was antigen and disease specific. Most importantly, one CD8+ clone could reverse the ongoing disease. These new therapeutic approaches derived from animal models may offer a hope of more selective interventions for the treatment of human autoimmune diseases.