Sudhakar Reddy Kalluri 1 , Veit Rothhammer 1 , Ori Staszewski 2 , Rajneesh Srivastava 1 , Franziska Petermann 1 , Marco Prinz 2 , Bernhard Hemmer 1 , Thomas Korn 1 * 1 Department of Neurology, Klinikum rechts der Isar, Technische Universit?t M?nchen, M?nchen, Germany, 2 Department of Neuropathology, Institute of Pathology, Universit?tsklinikum Freiburg, Freiburg, Germany Abstract? Background Antibodies to the water channel protein aquaporin-4 (AQP4), which is expressed in astrocytic endfeet at the blood brain barrier, have been identified in the serum of Neuromyelitis optica (NMO) patients and are believed to induce damage to astrocytes. However, AQP4 specific T helper cell responses that are required for the generation of anti-AQP4 antibodies and most likely also for the formation of intraparenchymal CNS lesions have not been characterized.
BACKGROUND: Neuromyelitis optica (NMO), a severe demyelinating disease, represents itself with optic neuritis and longitudinally extensive transverse myelitis. Serum NMO-IgG autoantibodies (Abs), a specific finding in NMO patients, target the water channel protein aquaporin-4 (AQP4), which is expressed as a long (M-1) or a short (M-23) isoform.
Neuromyelitis optica (NMO) is an inflammatory autoimmune demyelinating disease of the central nervous system (CNS) which in autoantibodies produced by patients with NMO (NMO-IgG) recognize a glial water channel protein, Aquaporin-4 (AQP4) expressed as two major isoforms, M1- and M23-AQP4, in which the plasma membrane form orthogonal arrays of particles (OAPs). AQP4-M23 is the OAP-forming isoform, whereas AQP4-M1 alone is unable to form OAPs.
There is evidence that the presence of Aquaporin-4 is directly involved in the pathogenesis ofNMO. AQP-4 Ab is thought to bind to an extra-ceLlular domain of the target protein and the E-loop was suggested as a probable candidate epitope. Molecular mimicry namely structural similarity between epitopes contained within microbial and host proteins, leading to cross-reactive Ab’s in the host has been discussed.