Objective: Guillain-Barré syndrome (GBS) is a postinfectious neuropathy most frequently caused by Campylobacter jejuni. Lipo-oligosaccharides (LOS), expressed by C. jejuni induce antibodies that cross-react with self-glycolipids in peripheral nerves, causing neuropathy. Less than 1 in 1,000 persons infected with C. jejuni develop GBS, and the factors that determine GBS susceptibility are poorly understood. We hypothesized that these persons have a high intrinsic dendritic cell (DC) response to C. jejuni LOS through Toll-like receptor 4 (TLR4) activation. Methods: Intrinsic DC responsiveness to C. jejuni LOS was investigated first in 20 healthy controls at three time points with a 3-month interval, and second in patients, who previously developed GBS after a C. jejuni infection (n = 27) and controls (n = 26). Results: The DC response to C. jejuni LOS was highly variable between, but not within, healthy individuals, suggesting that intrinsic factors determine the magnitude of TLR4-mediated innate response. High responsiveness to C. jejuni LOS by former GBS patients was evidenced by increased expression of CD38 and CD40. Frequency of CD38, CD40 and type I interferon high responders was significantly increased in the GBS group. Interpretation: These results suggest that a strong response to TLR4 stimulation is a critical host condition for the development of GBS after an infection with C. jejuni.

doi.org/10.1002/ana.24442, hdl.handle.net/1765/88379
Annals of Neurology
Department of Immunology

Huizinga, R., van den Berg, B., van Rijs, W., Tio-Gillen, A., Fokkink, W.-J., Bakker-Jonges, L., … Jacobs, B. (2015). Innate Immunity to Campylobacter jejuni in Guillain-Barré Syndrome. Annals of Neurology, 78(3), 343–354. doi:10.1002/ana.24442