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Etude physiopathologique de la réponse immunitaire au cours de la thrombopénie immunologique (purpura thrombopénique immunologique)

Abstract : Immune thrombocytopenia (ITP) is an autoimmune disease responsible for a peripheral immune destruction of platelets associated with an inappropriate bone marrow production. In this work, we first review the mechanisms involved in the pathogenesis of ITP. We also focus on the T cell immune response, highlighting the key role of regulatory T cells (Treg) in peripheral tolerance. The implication of the spleen in the immune response and the effects of rituximab, a B cell depleting therapy, are discussed. Then, our results obtained from 40 ITP patients are reported. Despite the fact that CD4+CD25HighFoxp3+ circulating Treg levels are similar between patients and controls, a significant increase is observed in responder patients. In the spleen, the rate of Treg is lower in ITP patients. Analyses of the spleens also reveal an increase in the level of marginal zone B cells in ITP. Rituximab is responsible for a complete depletion of both circulating and splenic B cells, which is not sufficient to achieve a response. Moreover, plasma cells are still observed after treatment. An increase in the Th1/Treg ratio in the spleen of non responder patients after rituximab infusion could trigger an escape to this therapy. The involvement of CD8+ T cells in the pathogenesis of ITP is highlighted by the increase in the CD8+/CD4+ ratio in the spleen after rituximab. New fields in the understanding of the pathogenesis of ITP are opened with these results, particularly by showing a quantitative deficiency in splenic Treg and the possible involvement of marginal zone B cells. Regarding rituximab effect on the immune response, we demonstrate on the one hand that complete circulating and splenic B cell depletion is not sufficient to achieve remission, and on the other hand that Th1 response and increase in CD8+ T cells level may represent an escape to this treatment.
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Sylvain Audia. Etude physiopathologique de la réponse immunitaire au cours de la thrombopénie immunologique (purpura thrombopénique immunologique). Sciences agricoles. Université de Bourgogne, 2010. Français. ⟨NNT : 2010DIJOS073⟩. ⟨tel-00687984⟩

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