Mycoplasma pneumoniae infection often causes various neurological complications of both the central nervous system (CNS) and the peripheral nervous system. We retrospectively investigated the IgM and IgG antibodies to nine glycolipids [GM1, GM2, GM3, GD1a, GD1b, GD3, GT1b, GQ1b, and Gal-C (galactocerebroside)] and clinical features in neurological diseases associated with M. pneumoniae infection diagnosed in multiple hospitals throughout Japan between September 2010 and March 2012. Of the 46 patients with neurological diseases associated with M. pneumoniae infection, 27 were diagnosed with Guillain-Barré syndrome (GBS), 2 with Fisher syndrome (FS), 16 with CNS diseases, and 1 with both GBS and CNS disease. Anti-Gal-C IgM and IgG antibodies were most frequently detected (23/46, 50%). Patients with CNS diseases were younger than patients with GBS or FS, and IgM antibodies to Gal-C were more frequently detected in the patients with CNS diseases (41%) than in those with GBS or FS (13%). Of the nine patients who were positive for anti-Gal-C IgM antibody but lacked IgG antibody, we found the class-switch of anti-Gal-C antibody from IgM to IgG in two patients. The IgG antibodies appeared during their recovery phase, and the IgG belonged to the IgG1 subclass. Anti-Gal-C antibodies are closely associated with neurological diseases after M. pneumoniae infection. Particularly, anti-Gal-C IgM antibody is more frequently detected in younger patients affected with CNS involvement. The class-switch from IgM to IgG sometimes occurs in anti-Gal-C antibodies.

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A patient with xerostomia and xerophthalmia due to Sjögren's syndrome presented with acute motordominant polyneuropathy and multiple mononeuropathy with antiganglioside antibodies. Nerve conduction studies and a sural nerve biopsy revealed the neuropathy as a mixture of segmental demyelination and axonal degeneration. Positive results were obtained for several antiganglioside antibodies. Corticosteroid treatment proved effective. The neuropathy was considered to represent a mixture of polyneuropathy as Guillain-Barré syndrome and multiple mononeuropathy via Sjögren's syndrome. We speculate that Guillain-Barré syndrome occurred in the patient and Guillain-Barré syndrome itself activated multiple mononeuropathy via Sjögren's syndrome.

Chondroitin sulfate proteoglycans (CSPGs) are the main component of the extracellular matrix in the central nervous system (CNS) and influence neuroplasticity. Although CSPG is considered an inhibitory factor for nerve repair in spinal cord injury, it is unclear whether CSPG influences the pathogenetic mechanisms of neuroimmunological diseases. We induced experimental autoimmune encephalomyelitis (EAE) in chondroitin 6-O-sulfate transferase 1-deficient (C6st1(-/-)) mice. C6ST1 is the enzyme that transfers sulfate residues to position 6 of N-acetylgalactosamine in the sugar chain of CSPG. The phenotypes of EAE in C6st1(-/-) mice were more severe than those in wild-type (WT) mice were. In adoptive-transfer EAE, in which antigen-reactive T cells from WT mice were transferred to C6st1(-/-) and WT mice, phenotypes were significantly more severe in C6st1(-/-) than in WT mice. The recall response of antigen-reactive T cells was not significantly different among the groups. Furthermore, the number of pathogenic T cells within the CNS was also not considerably different. When EAE was induced in C6ST1 transgenic mice with C6ST1 overexpression, the mice showed considerably milder symptoms compared with those in WT mice. In conclusion, the presence of sulfate at position 6 of N-acetylgalactosamine of CSPG may influence the effecter phase of EAE to prevent the progression of pathogenesis. Thus, modification of the carbohydrate residue of CSPG may be a novel therapeutic strategy for neuroimmunological diseases such as multiple sclerosis.

Proteoglycans (PGs) are the components of extracellular matrices in the central nervous system (CNS). Keratan sulfate (KS) is a glycosaminoglycan that is included in the KSPG that acts as an inhibitory factor in nerve regeneration after CNS injury. To investigate the role of KS in immune diseases, we induced experimental autoimmune encephalomyelitis (EAE) in mice that were deficient in the N-acetylglucosamine (GlcNAc)-6-O-sulfotransferase 1 (GlcNAc6ST1) gene (KS-KO). KS-KO mice developed less severe EAE and showed repressed recall response in the induction phase. Furthermore, GlcNAc6ST1 might have roles in the passage of the pathogenic lymphocytes through the blood-brain barrier via adhesion molecules. Thus, modulation of KS may become a treatment for neuroimmunological diseases.