IgG marker of optic-spinal multiple sclerosis binds to the aquaporin-4 water channel
Vanda A Lennon, Thomas J Kryzer, Sean J Pittock, A S Verkman, Shannon R Hinson, Vanda A Lennon, Thomas J Kryzer, Sean J Pittock, A S Verkman, Shannon R Hinson
Abstract
Neuromyelitis optica (NMO) is an inflammatory demyelinating disease that selectively affects optic nerves and spinal cord. It is considered a severe variant of multiple sclerosis (MS), and frequently is misdiagnosed as MS, but prognosis and optimal treatments differ. A serum immunoglobulin G autoantibody (NMO-IgG) serves as a specific marker for NMO. Here we show that NMO-IgG binds selectively to the aquaporin-4 water channel, a component of the dystroglycan protein complex located in astrocytic foot processes at the blood-brain barrier. NMO may represent the first example of a novel class of autoimmune channelopathy.
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References
- Misu, T., K. Fujihara, I. Nakashima, I. Miyazawa, N. Okita, S. Takase, and Y. Itoyama. 2002. Pure optic-spinal form of multiple sclerosis in Japan. Brain. 125:2460–2468.
- Lucchinetti, C.F., R.N. Mandler, D. McGavern, W. Bruck, G. Gleich, R.M. Ransohoff, C. Trebst, B. Weinshenker, D. Wingerchuk, J.E. Parisi, and H. Lassman. 2002. A role for humoral mechanisms in the pathogenesis of Devic's neuromyelitis optica. Brain. 125:1450–1461.
- Mandler, R.N., L.E. Davis, D.R. Jeffery, and M.K. Kornfeld. 1993. Devic's neuromyelitis optica: a clinicopathological study of 8 patients. Ann. Neurol. 34:162–168.
- Wingerchuk, D.M., W.F. Hogancamp, P.C. O'Brien, and B.G. Weinshenker. 1999. The clinical course of neuromyelitis optica (Devic's syndrome). Neurology. 53:1107–1114.
- Wingerchuk, D.M., and B.G. Weinshenker. 2003. Neuromyelitis optica: clinical predictors of a relapsing course and survival. Neurology. 60:848–853.
- Keegan, M., A.A. Pineda, R.L. McClelland, C.H. Darby, M. Rodriguez, and B.G. Weinshenker. 2002. Plasma exchange for severe attacks of CNS demyelination: predictors of response. Neurology. 58:143–146.
- Lennon, V.A., D.M. Wingerchuk, T.J. Kryzer, S.J. Pittock, C.F. Lucchinetti, K. Fujihara, I. Nakashima, and B.G. Weinshenker. 2004. A serum autoantibody marker of neuromyelitis optica: distinction from multiple sclerosis. Lancet. 364:2106–2112.
- Mandler, R.N., W. Ahmed, and J.E. Dencoff. 1998. Devic's neuromyelitis optica: a prospective study of seven patients treated with prednisone and azathioprine. Neurology. 51:1219–1220.
- Goodin, D.S., E.M. Frohman, G.P. Garmany Jr., J. Halper, W.H. Likosky, F.D. Lublin, D.H. Silberberg, W.H. Stuart, and S. van den Noort. 2002. Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and the MS Council for Clinical Practice Guidelines. Disease modifying therapies in multiple sclerosis: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and the MS Council for Clinical Practice Guidelines. Neurology. 58:169–178.
- Moore, S.A., F. Saito, J. Chen, D.E. Michele, M.D. Henry, A. Messing, R.D. Cohn, S.E. Ross-Barta, S. Westra, R.A. Williamson, et al. 2002. Deletion of brain dystroglycan recapitulates aspects of congenital muscular dystrophy. Nature. 418:422–425.
- Ma, T., B. Yang, A. Gillespie, E.J. Carlson, C.J. Epstein, and A.S. Verkman. 1997. Generation and phenotype of a transgenic knockout mouse lacking the mercurial-insensitive water channel aquaporin-4. J. Clin. Invest. 100:957–962.
- Amiry-Moghaddam, M., R. Xue, F.M. Haug, J.D. Neely, A. Bhardwaj, P. Agre, M.E. Adams, S.C. Froehner, S. More, and O.P. Otterson. 2004. Alpha syntrophin deletion removes the perivascular but not the endothelial pool of aquaporin-4 at the blood-brain barrier and delays the development of brain edema in an experimental model of acute hyponatremia. FASEB J. 18:542–544.
- Frigeri, A., G.P. Nicchia, B. Nico, F. Quondamatteo, R. Herken, L. Roncali, and M. Svelto. 2001. Aquaporin-4 deficiency in skeletal muscle and brain of dystrophic mdx mice. FASEB J. 15:90–98.
- Vajda, Z., M. Pedersen, E.-M. Füchtbauer, K. Wertz, H. Stødkilde-Jørgensen, E. Sulyok, T. Dóczi, J.D. Neely, P. Agre, J. Frøkiaer, and S. Nielsen. 2002. Delayed onset of brain edema and mislocalization of aquaporin-4 in dystrophin-null transgenic mice. Proc. Natl. Acad. Sci. USA. 99:13131–13136.
- Jung, J.S., R.V. Bhat, G.M. Preston, W.B. Guggino, J.M. Baraban, and P. Agre. 1994. Molecular characterization of an aquaporin cDNA from brain: candidate osmoreceptor and regulator of water balance. Proc. Natl. Acad. Sci. USA. 91:13052–13056.
- Nico, B., A. Frigeri, G.P. Nicchia, F. Quondamatteo, R. Herken, M. Errede, D. Ribatti, M. Svelto, and L. Roncali. 2001. Role of aquaporin-4 water channel in the development and integrity of the blood-brain barrier. J. Cell Sci. 114:1297–1307.
- Amiry-Moghaddam, M., D.S. Frydenlund, and O.P. Ottersen. 2004. Anchoring of aquaporin-4 in brain: molecular mechanisms and implications for the physiology and pathophysiology of water transport. Neuroscience. 129:999–1010.
- Hasegawa, H., T. Ma, W. Skach, M. Matthay, and A.S. Verkman. 1994. Molecular cloning of a mercurial insensitive water channel expressed in selected water transporting tissues. J. Biol. Chem. 269:5497–5500.
- Manley, G.T., M. Fujimura, T. Ma, N. Noshita, F. Filiz, A.W. Bollen, P. Chan, and A.S. Verkman. 2000. Aquaporin-4 deletion in mice reduces brain edema after acute water intoxification and ischemic stroke. Nat. Med. 6:159–163.
- Agre, P., and D. Kozono. 2003. Aquaporin water channels: molecular mechanisms for human diseases. FEBS Lett. 555:72–78.
- Saadoun, S., M.C. Papadopoulos, D.C. Davies, S. Krishna, and B.A. Bell. 2002. Aquaporin-4 expression is increased in oedematous human brain tumours. J. Neurol. Neurosurg. Psychiatry. 72:262–265.
- Papadopoulos, M.C., S. Krishna, G.T. Manley, and A.S. Verkman. 2004. Aquaporin-4 facilitates the reabsorption of excess fluid in vasogenic brain edema. FASEB J. 18:1291–1293.
- Brimijoin, S., P. Hammond, M. Balm, and V. Lennon. 1991. Experimental autoimmunity to brain acetylcholinesterase. Cholinesterases: Structure, Function, Mechanism, Genetics, and Cell Biology. J Massoulié, F. Bacou, E. Barnard, A. Chatonnet, B. Doctor, D.M. Quinn, editors. American Chemical Society, Washington DC. 332–335.
- Poduslo, J.F., and G.L. Curran. 2001. Amyloid β peptide as a vaccine for Alzheimer's disease involves receptor-mediated transport at the blood-brain barrier. Neuroreport. 12:3197–3200.
- Lucchinetti, C., W. Brück, J. Parisi, B. Scheithauer, M. Rodriguez, and H. Lassmann. 2000. Heterogeneity of multiple sclerosis lesions: implications for the pathogenesis of demyelination. Ann. Neurol. 47:707–717.
- Lennon, V.A., E.H. Lambert, and G.E. Griesmann. 1984. Membrane array of acetylcholine receptors determines complement-dependent mononuclear phagocytosis in experimental myasthenia gravis. Fed. Proc. 43:1764.
- Lennon, V.A. 1978. Myasthenia gravis: a prototype immunopharmacological disease. The Menarini Series on Immunopathology. P.A. Miescher, editor. Schwabe & Co., Basel. 178–198.
- Lennon, V.A., L.G. Ermilov, J.H. Szurszewski, and S. Vernino. 2003. Immunization with neuronal nicotinic acetylcholine receptor induces neurological autoimmune disease. J. Clin. Invest. 111:907–913.
- Vernino, S., L.G. Ermilov, L. Sha, J.H. Szurszewski, P.A. Low, and V.A. Lennon. 2004. Passive transfer of autoimmune autonomic neuropathy to mice. J. Neurosci. 24:7037–7042.
Source: PubMed