Thus, this topic was reviewed in a presentation held during the 1st Panhellenic Congress of Autoimmune Diseases, Rheumatology and Clinical Immunology in Portaria, Pelion, Greece. Portaria, Pelion, Greece. For acute IMPN, often referred to as Guillain-Barr syndrome and its variants, several serological markers including autoAbs to gangliosides and sulphatide have been employed successfully in clinical routine. However, the evolution of serological diagnosis of chronic variants, such as chronic inflammatory demyelinating polyneuropathy or multifocal motor neuropathy, is less satisfactory. Serological diagnostic markers could, therefore, help in the differential diagnosis due to their assumed pathogenic role. Additionally, stratification of patients to improve their response to treatment may be possible. In general, a majority of patients respond well to causal therapy that includes intravenous immunoglobulins and plasmapheresis. As second line therapy options, biologicals (e.g., rituximab) and immunosuppressant or immunomodulatory drugs may be considered when patients do not respond adequately. Keywords:immune-mediated polyneuropathy, ganglioside, sulphatide, autoantibody == Glycolipids as autoantigenic targets == Among antiglycolipid autoantibodies (autoAbs), those directed to gangliosides have been investigated best in the context of autoimmune nerve illnesses.13The occurrence of autoAbs to glycolipids is often preceded by infections in particular intestinal ones (Campylobacter [C.] jejuni). Hence, molecular mimicry has been considered as most common reason for the development of a tolerance break to glycolipids in the context of IMPN pathophysiology.4There is, for instance, a striking similarity of glycan structures present onC. jejunilipo-oligosaccharides with gangliosides including GM1, GM2, GD1a, GT1a and GD3.5 Interestingly, gangliosides also represent tumour-associated antigens often overexpressed in distinct malignancies, against which the immune system can exert effector mechanisms in the context of tumour surveillance and corresponding antitumor responses.6The assumption that a tolerance break against gangliosides can be part of antitumor Tioconazole responses during tumorigenesis is an interesting topic; however, it is beyond the scope of this review. The term ganglioside introduced by Ernst Klenk in 1942 is a combination of the two termsganglionandglycoside, which refers to the location and composition of these molecules, respectively.7Gangliosides are integrated into the cell membrane and are probably located in lipid rafts.8,9Gangliosides consist of a ceramide and an oligosaccha-ride moiety with, in general, one or more neuraminic acid residues commonly referred to as sialic acids. The ceramide part is embedded in the outer leaflet of the plasma membrane and the oligosaccharides directed to the extracellular surface (Figure 1).8Ganglioside molecules with more than two neuraminic acid residues are mainly found in the nervous system, where they can partake in cell signal transduction events. However, they Rabbit Polyclonal to ZC3H11A are also accessible for autoimmune attacks at special locations such as the dorsal and ventral spinal roots or the sensory and motor nerve terminals.10In contrast, the larger part of the peripheral nervous system is less exposed due to the blood-nerve barrier generating immunologically privileged sites.3Altogether, the prevalence of ganglio-sides in peripheral nerves is quite variable and there is a need for more precise data on the composition and distribution of gangliosides.3,11The rare involvement of the central nervous system during a tolerance break to Tioconazole glycolipids is very likely caused by the blood-brain barrier limiting the crossover of autoAbs in the brain. == Figure 1. == Localization of the ganglioside GT1b in the outer leaflet of the plasma membrane of nerve cells. The ceramide moiety is hidden in the outer phospholipid layer of the membrane and presumably surrounded by phospholipids, cholesterol and transmembrane molecules forming a lipid raft. Gal: galactose; Glu: glucose; GluNAc: N-acetyl glycosamine; NeuNAc: N-acetyl neuraminic acid (sialic acid) Since peripheral nerves exert motor, sensory and autonomic functions, the site and extent of autoimmune attack against them should have a direct impact on the characteristics of the occurring clinical symptoms in patients with IMPN. Notably, in extraneural tissues, the ganglioside content is one to two orders of magnitude lower than in the nervous system.12That may explain the almost negligible effect of a specific autoimmune attack against them at these sites. In contrast to gangliosides, sulphatide such as 3-O-sulphogalactosylceramide represent a class of glycolipids with a sulphate group instead of neuraminic acid. These sulphoglycolipids differ in their strong negative charge (pKa -1.8) from the gangliosides. In the peripheral nervous system, sulphatide is mainly found in the non-compact myelin Tioconazole of Schwann cells, where they make up about 47% of all myelin lipids and are essential for the integrity of the myelin sheath.13When sulphatide is.