Identification, validation, and characterization of novel autoantigens of chronic inflammatory demyelinating polyneuropathy (CIDP)

• Applicant: Dr. Christian Moritz
• Subject Area: Molecular and Cellular Neurology and Neuropathology ; Clinical Neurology; Neurosurgery and Neuroradiology
• Term: from 2017 to 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 336225839

The aim of my project is to identify autoantigens in the blood serum of patients with the disabling neuronal autoimmune disease named chronic inflammatory demyelinating polyneuropathy (CIDP). Patients with this disease suffer from progressively increasing limb weakness, lack of voluntary coordination of muscle movements (ataxia), absent or diminished tendon reflexes, and sensation of prickling or burning (paresthesia). Identifying the autoantigens of this disease will improve its diagnosis, treatment, and understanding. Recent studies failed to identify an antigen for the majority of patients, since the researchers either used a restricted targeted approach finding their protein-of-interest only in a rare subgroup of patients, or lost interesting but difficult-to-handle proteins during their preparation. To overcome these issues, I will apply two approved untargeted approaches aiming at novel antigens. Further, I performed preliminary experiments to adapt the sample preparation and electrophoresis to the project needs. As a result, I significantly improved the accessibility and resolution of intractable high-molecular-weight proteins, as they can be found at one of the interesting target regions, namely the node of Ranvier. Thus, I am convinced that my study represents innovative and original advancements allowing to identify the missing candidate(s). My access to the local biobank including hundreds of precious serum samples completes the feasibility of my approach. The first step -- the identification -- will include (1) immunoprecipitation using human serum antibodies to capture corresponding antigens of nerve tissue of rats and cows and (2) 1D+2D protein electrophoresis of nerve tissue proteins, followed by serum incubation. Both approaches will apply highly sensitive mass spectrometry to identify the bound antigens. By applying appropriate statistics, I will isolate protein candidates that appeared in the patient group, but not in the control group (both healthy controls and other neurological diseases). By enzyme-linked immunosorbent assays (ELISA), cell-based assays, and immunoblots, I will validate interesting candidates and assess their sensitivity and specificity as a biomarker. My project will help to understand the role of autoantibodies in CIDP's pathophysiology and will provide new biomarkers improving the diagnosis and treatment of autoimmune disorders. Further, I will significantly extend my skills to a new scientific field, i.e., medical research, and learn important methods being applied for any antibody-related autoimmune disease. Thus, also the medical research in Germany will benefit from my obtained expertise in the future.

• DFG Programme: Research Fellowships
• International Connection: France
• Hosts: Professor Dr. Jean-Christophe Antoine; Professor Dr. Jérôme Honnorat