Project Grant R21NS150176

The National Institute of Neurological Disorders and Stroke awarded The Ohio State University $234,006 on September 1, 2026, under the Extramural Research Programs in the Neurosciences and Neurological Disorders program (CFDA 93.853) to develop a novel pipeline for antigen discovery in Guillain-Barré Syndrome using single-cell T-cell receptor data and artificial intelligence-based ligand prediction.

The project addresses the gap between GBS pathogenesis—driven by molecular mimicry in which immune responses to preceding infections cross-react with self-antigens on peripheral nerves—and current therapies that act non-specifically. Current treatments including plasma exchange and intravenous immunoglobulin do not target the root cause, leaving up to one-third of patients with severe, long-term neurological deficits. The research team has generated preliminary single-cell TCR-sequencing data characterizing cerebrospinal fluid at disease diagnosis, revealing clonally expanded, activated CD4+ and CD8+ effector T cells distinct from blood populations. Using the TCROSS artificial intelligence platform, in-silico analysis identified a molecular mimicry axis linking a Campylobacter jejuni protein to human NPC1, a lipid transporter essential for Schwann cell myelin maintenance. The work will characterize dominant CSF-resident T-cell clones and validate pathogenic antigens as targets for antigen-specific therapeutic intervention.

Work is performed in Columbus, Ohio, with a period of performance from September 1, 2026, through August 31, 2028.