Project: Measuring autoantigen-specific T cells as new diagnostic sensors and therapeutic targets in neuromyelitis optica

Acronym AspecT-NMO (Reference Number: EJPRD19-195)
Project Topic Neuromyelitis optica spectrum of disorders (NMOSD) form a rare group of severe antibody-mediated autoimmune diseases (AID) requiring livelong therapy with severe side effects. The identification of aquaporin-4 (AQP4) as a specific target autoantigen in NMO differentiated it from multiple sclerosis (MS). Autoantigen-specific T cells are centrally involved in the pathogenesis of these diseases via the regulation of pathogenic antibodies. However, their NMOSD-associated phenotypic and functional alterations are still enigmatic. The characterization of autoreactive T cells provides a unique opportunity for specific diagnosis and therapies targeting the disease cause rather than the symptoms. Members of our consortium have established powerful technologies for unbiased identification and molecular characterization of autoantigen-specific CD4 T cells. In a proof of principle experiment we identified a unique and discriminative phenotype of ex vivo isolated AQP4-specific T cells in AQP4 antibody positive but not -negative NMOSD patients. We will now deeply characterize T cells against AQP4- and related autoantigens in large NMOSD patient cohorts and identify cross-reactivity to microbiota as potential trigger of the pathogenic response. Integration of a biotech company will allow to develop analysis tools optimized for rare auto-antigen-specific T cells and for their rapid application in clinical routine. Our project will pursue a unique technical approach to provide a basis for the development of auto-antigen-specific diagnostics and therapeutics.
Network EJP RD
Call 1st EJP RD Joint Transnational Call for Rare Diseases Research Project (JTC 2019)

Project partner

Number Name Role Country
1 Christian-Albrechts-Universität zu Kiel Coordinator Germany
2 Weizmann Institute of Science Partner Israel
3 Lyon University Hospital (HCL) Partner France
4 Neuroimmunology and MS Research Partner Switzerland
5 Institut Necker-Enfants Malades, INSERM U115-CNRS UMR 8253 Partner France
6 Miltenyi Biotec Partner Germany