Projet de thèse en Immunologie
Sous la direction de Luc Mouthon.
Thèses en préparation à l'Université de Paris (2019-....) , dans le cadre de 561 hématologie, oncogénèse et biothérapies , en partenariat avec Institut Cochin (equipe de recherche) depuis le 16-10-2018 .
Background: Pulmonary arterial hypertension is a substantial global health issue. Beside idiopathic PAH (IPAH), connective tissue disease (CTD)-related PAH is the second leading cause. Its pathogenesis is not fully understood but several arguments demonstrate a significant involvement of different players of immune system such as the presence of autoantibodies. Despite recent advances, the risk assessment of developing PAH complicating a CTD is not satisfactory. The identification of specific auto-antibodies and their antigenic targets could bring a diagnostic benefit, prognostic value and better knowledge of pathophysiological pathways implicated. Objective: To identify auto-antibodies and characterize their antigen targets in PAH associated to CTD, and to assess their pathogenic role. Methods: Patients with (N=182) or without (N=192) PAH associated or not with a connective tissue disease and included in the multicenter national Auto-HTAP trial (ClinicalTrials number: NCT01208792) will be assessed for auto-antibodies detection by immunoblot 1 dimension (1D), and identify antigen target by immunoblot 2D coupled with mass spectrometry. The immunological reactivities will be compared between groups, with or without PAH. Based on proteomic pathways identified, supplementary explorations of mechanical tracks will be conducted, as well as the development of high-throughput serum screening techniques. Expected results: Identification of specific autoantibodies and of antigen targets associated to CTD-induced PAH, and validation of prognosis immunological biomarkers. That will allow to develop throughput serum screening test, and finally to provide additional pathophysiological knowledge about CTD associated PAH.
Study of auto-antibodies in pulmonary arterial hypertension (PAH) associated with connective tissue diseases (CTD)
Pas de résumé disponible.