Antibodies in Guillain-Barré syndrome, the immune system’s double-edged sword 2332889

Abstract

Abstract Introduction Campylobacter jejuni is a leading cause of bacterial gastroenteritis worldwide, and a majority of isolates express an outer layer of lipooligosaccharides (LOS) that mimic human gangliosides. In approximately 1:1,000 cases of C. jejuni infection, there is a breakdown of self-tolerance resulting in antibody generation against the LOS mimics that cross-react with gangliosides found abundantly on human neurons. Opsonized neurons are then destroyed via complement and phagocyte recruitment, leading to the autoimmune paralysis known as Guillain-Barré syndrome (GBS). Our lab has observed a subset of former GBS patients possess high levels of circulating anti-ganglioside IgG one decade after recovery. Methods Serum was collected from GBS patients (acute phase and post-GBS), C. jejuni-only enteritis patients, and healthy donors. We then assessed anti-ganglioside responses via ELISA. Additionally, immune responses were analyzed by western blotting and opsonophagocytosis assays using C. jejuni-expressing ganglioside-mimicking LOS. IgG glycosylation was analyzed via liquid chromatography-mass spectrometry (LC-MS). Results Circulating anti-GM1 antibodies were observed in 10% of GBS recovered donors, 3% of healthy donors, and 0% of enteritis donors. Anti-GM1 positive sera cross-reacted with GM1-mimicking LOS and significantly killed C. jejuni at higher levels than anti-GM1 negative sera. LC-MS analyses indicate a shift towards anti-inflammatory carbohydrate modifications on IgG in the recovered donors. Conclusion Through understanding the differences in immune responses in acute-phase versus recovered GBS patients, improved therapeutics for GBS treatment can be developed. Funding Source NIAID R21AI175925, DoD CDMRP PR181475 Topic Categories Basic Autoimmunity (BA)