Ingrid 't Hart

16 Chapter 1 1 1.3 GSLs in the autoimmune disease Guillain-Barré Syndrome Most an�bodies are formed upon infec�on by bacteria, viruses or parasites to detect and remove the pathogens from the human body. Occasionally, an�bodies can become cross-reac�ve towards endogenous an�gens by molecular mimicking of the pathogen, which can result in auto-immune diseases. 74 Guillain-Barré syndrome (GBS) is an autoimmune disease where the peripheral nervous system (PNS) is damaged. GBS is rare disease (0.6-4/100,000 persons/year) and symptoms vary from �ngling sensa�on to complete muscular failure. 3,75,76 This auto-immune disease is in 25-33% of the cases preceded by Campylobacter jejuni infec�on. 75,76,77 However, not all C. jejuni infec�ons lead to GBS, sugges�ng factors of the host are also of importance. 78 GBS can be divided in two subtypes: acute inflammat ory demyelina�ng polyneuropathy (AIDP) and axonal subtypes such as acute motor axonal degenera�on neuropathy (AMAN) and acute motor and sensory axonal neuropathy (AMSAN). 77 AIDP is characterized by segmental demyelina�on and secondary axonal damage. Upon molecular mimicry, T-cells are ac�vated and damage the myelin sheet together with produced cytokines and radicals. AMAN is the second most common subtype and the main feature is axonal degenera�on. In AMAN, molecular mimicry also seems to play a key role. High similarity is found between C. jejuni ganglioside mimics and host gangliosides that are mainly present on motor axons, such as: GM1a, GM1b and GD1a. 78 An�-ganglioside an�bodies against GD1b, GT1a, GT1b and GQ1b have been detected in GBS as well. 79 The gram-nega�ve bacterium C. jejuni can carry ganglioside mimics on its lipooligosaccharide (LOS), which forms an important component of the bacterial outer membrane (Fig. 7). 80,81,82,83 Although the exact func�on of C. jejuni’ s molecular mimicry is unknown, it plays a key role in GBS. 3,74,84 Different mechanisms have been proposed for the immune response on ganglioside mimics affec�ng myelin or axons, however much needs to be elucidated. It seems that humoral immunity is the major pathway in the AMAN subtype. Overall, an�-ganglioside an�bodies are frequently found in serum of GBS pa�ents: for AIDP up to 62% and for AMAN up to 80%. 78 Addi�onally, an�ganglioside an�bodies from GBS serum samples have not only found to be directed towards the single gangliosides, but also to complexes, such as GD1a/GD1b or GQ1b/ GM1. 85 These gangliosides and an�bodies are useful biomarkers to guide treatment and provide possible new therapeu�c targets.