DOWNLOAD ~ Anti-Aquaporin-4 Antibodies in Neuromyelitis Optica: How to Prove Their Pathogenetic Relevance?(Editorial) # by The International MS Journal ~ eBook PDF Kindle ePub Free

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Title: Anti-Aquaporin-4 Antibodies in Neuromyelitis Optica: How to Prove Their Pathogenetic Relevance?(Editorial)
Author : The International MS Journal
Release Date : January 01, 2008
Genre: Health & Fitness,Books,Health, Mind & Body,
Pages : * pages
Size : 206 KB

Description

The discovery of a specific autoantibody response in neuromyelitis optica (NMO) patients, which selectively targets astrocytic end feet at the glia limitans (1) and which is directed against the water channel aquaporin-4 (AQP-4) (2) was a milestone in defining this disease entity and profoundly changed our view regarding its pathogenesis. (3) Indirect evidence, coming from clinical observations and pathology strongly suggest that these autoantibodies play a major role in driving the disease process. The pathological hallmark of NMO lesions is a very selective and characteristic deposition of immunoglobulins and complement on astrocytes at the glia limitans, which is associated with destruction and loss of glial fibrillary acidic protein and AQP-4 positive astrocytes in fresh lesions (4-6) followed by demyelination and global tissue destruction. As in other antibody-mediated diseases, granulocytes, and in particular eosinophils, are a major component of the inflammatory infiltrates. (4) Furthermore, the distribution of the lesions in the brain and spinal cord of NMO patients correlates with the extent of regional AQP-4 expression. (6,7) Most importantly, therapies, which eliminate antibodies (plasma exchange), (8) or which target Blymphocytes (anti-CD20 antibodies), (9) are at least in part effective in NMO patients. Based on this evidence NMO is now considered an antibody-mediated autoimmune disease, however, direct proof of the pathogenic potential of AQP-4 antibodies is so far lacking. To firmly establish the pathogenic role of autoantibodies, it has to be shown in vivo that pathological changes, which are identical or at least similar to NMO, can be induced by the transfer of such antibodies in an experimental model. To achieve this, several essential requirements have to be fulfilled. 1) The expression of the target epitope of the autoantibodies has to be similar between humans and the animal species, in which transfer is performed. So far, the molecular configuration of the epitope, which is recognized by NMO associated AQP-4 autoantibodies is unknown. (10) Although potential binding sites have been identified through the knowledge obtained from the crystal structure of AQP-4, it is not clear yet whether these antibodies recognize a linear or a conformational epitope. Thus the simple approach, comparing the amino acid sequence of potential binding sites between humans and rodents, is not possible. However, it has been shown that some, but not all NMO sera bind to rodent astrocytes in tissue sections in a similar extent as they do on cell lines, transfected with human AQP-4. (1,11) This indicates that disease transfer into rodents (rats or mice) may be feasible with NMO-IgG fractions from some, but not all patients.