This project will examine the structural and immunological similarities (the basis of 'molecular mimicry') between microbial glycolipids and the acylated-cerebrosides that we have characterized for both their precise chemical structure, and their presence in a substantial amount in myelin. The study will examine: (1) the cross-reactivity between the binding of the acyl-carbohydrates of myelin and microbes, (2) their binding to the oligoclonal immunoglobulins found in MS CSF and (3) cellular immune responses (T cells, NKT cells and innate immunity) in lymphocytes in the circulation and in CSF in MS and controls. This work can delineate both the structure and function of novel and significant molecular structures that play important roles in demyelination and may play a causative role in demyelination. Optimally, the project could lead to defining a mechanism by which mycoplasmas initiate the immune events that lead to inflammatory demyelination or even directly cause the inflammatory cascade by mycoplasma infection of CMS or elsewhere in the body. A pathogenic role in triggering the autoimmune disorder could also emerge from the findings. Furthermore, an assay of the myelin cerebroside derivatives that offers a novel opportunity to measure myelin constituents in relation to type, stage, and activity of MS could yield useful approaches for diagnosis and determination of disease activity. ? ?
| Hogan, Edward L; Podbielska, Maria; O'Keeffe, Joan (2013) Implications of Lymphocyte Anergy to Glycolipids in Multiple Sclerosis (MS): iNKT Cells May Mediate the MS Infectious Trigger. J Clin Cell Immunol 4: |
| Podbielska, Maria; Levery, Steven B; Hogan, Edward L (2011) The structural and functional role of myelin fast-migrating cerebrosides: pathological importance in multiple sclerosis. Clin Lipidol 6:159-179 |
| Jana, Arundhati; Hogan, Edward L; Pahan, Kalipada (2009) Ceramide and neurodegeneration: susceptibility of neurons and oligodendrocytes to cell damage and death. J Neurol Sci 278:5-15 |
| O'Keeffe, Joan; Gately, Carol M; Counihan, Timothy et al. (2008) T-cells expressing natural killer (NK) receptors are altered in multiple sclerosis and responses to alpha-galactosylceramide are impaired. J Neurol Sci 275:22-8 |
