The DOI matches its Crossref record; 30 of the 30 references it cites were found in a registry or an index.
Aquaporin-4–binding autoantibodies in patients with neuromyelitis optica impair glutamate transport by down-regulating EAAT2
Open accessAbstract
Neuromyelitis optica (NMO)-immunoglobulin G (IgG) is a clinically validated serum biomarker that distinguishes relapsing central nervous system (CNS) inflammatory demyelinating disorders related to NMO from multiple sclerosis. This autoantibody targets astrocytic aquaporin-4 (AQP4) water channels. Clinical, radiological, and immunopathological data suggest that NMO-IgG might be pathogenic. Characteristic CNS lesions exhibit selective depletion of AQP4, with and without associated myelin loss; focal vasculocentric deposits of IgG, IgM, and complement; prominent edema; and inflammation. The effect of NMO-IgG on astrocytes has not been studied. In this study, we demonstrate that exposure to NMO patient serum and active complement compromises the membrane integrity of CNS-derived astrocytes. Without complement, astrocytic membranes remain intact, but AQP4 is endocytosed with concomitant loss of Na+-dependent glutamate transport and loss of the excitatory amino acid transporter 2 (EAAT2) . Our data suggest that EAAT2 and AQP4 exist in astrocytic membranes as a macromolecular complex. Transport-competent EAAT2 protein is up-regulated in differentiating astrocyte progenitors and in nonneural cells expressing AQP4 transgenically. Marked reduction of EAAT2 in AQP4-deficient regions of NMO patient spinal cord lesions supports our immunocytochemical and immunoprecipitation data. Thus, binding of NMO-IgG to astrocytic AQP4 initiates several potentially neuropathogenic mechanisms: complement activation, AQP4 and EAAT2 down-regulation, and disruption of glutamate homeostasis.
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Cites
Danbolt, N. C. (2001) · Progress in Neurobiology · doi:10.1016/s0301-0082(00)00067-8 · Cited by 4,227
IgG marker of optic-spinal multiple sclerosis binds to the aquaporin-4 water channel
Lennon, V. A., Kryzer, T. J., Pittock, S. J., Verkman, A. S., & Hinson, S. R. (2005) · The Journal of Experimental Medicine · doi:10.1084/jem.20050304 · Cited by 2,288
Self-citationThe spectrum of neuromyelitis optica
Wingerchuk, D. M., Lennon, V. A., Lucchinetti, C. F., Pittock, S. J., & Weinshenker, B. G. (2007) · The Lancet Neurology · doi:10.1016/s1474-4422(07)70216-8 · Cited by 2,179
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A role for humoral mechanisms in the pathogenesis of Devic's neuromyelitis optica
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Glutamate excitotoxicity in a model of multiple sclerosis
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Roemer, S. F., Parisi, J. E., Lennon, V. A., Benarroch, E. E., Lassmann, H., Bruck, W., Mandler, R. N., Weinshenker, B. G., Pittock, S. J., Wingerchuk, D. M., et al. (2007) · Brain · doi:10.1093/brain/awl371 · Cited by 716
Self-citationNeuromyelitis Optica and Non–Organ-Specific Autoimmunity
Pittock, S. J., Lennon, V. A., de Seze, J., Vermersch, P., Homburger, H. A., Wingerchuk, D. M., Lucchinetti, C. F., Zéphir, H., Moder, K., & Weinshenker, B. G. (2008) · Archives of Neurology · doi:10.1001/archneurol.2007.17 · Cited by 608
Self-citationNMDA receptors are expressed in developing oligodendrocyte processes and mediate injury
Salter, M. G., & Fern, R. (2005) · Nature · doi:10.1038/nature04301 · Cited by 553
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Molecular pathophysiology of cerebral edema
Stokum, J. A., Gerzanich, V., & Simard, J. M. (2016) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x15617172 · Cited by 587
Serologic diagnosis of NMO: A multicenter comparison of aquaporin-4-IgG assays
Waters, P. J., McKeon, A., Leite, M. I., Rajasekharan, S., Lennon, V. A., Villalobos, A., Palace, J., Mandrekar, J. N., Vincent, A., Bar-Or, A., et al. (2012) · Neurology · doi:10.1212/wnl.0b013e318248dec1 · Cited by 526
Self-citationJarius, S., Paul, F., Weinshenker, B. G., Levy, M., Kim, H. J., & Wildemann, B. (2020) · Nature Reviews Disease Primers · doi:10.1038/s41572-020-0214-9 · Cited by 478
Neuromyelitis optica unique area postrema lesions: Nausea, vomiting, and pathogenic implications
Popescu, B. F. G., Lennon, V. A., Parisi, J. E., Howe, C. L., Weigand, S. D., Cabrera-Gómez, J. A., Newell, K., Mandler, R. N., Pittock, S. J., Weinshenker, B. G., et al. (2011) · Neurology · doi:10.1212/wnl.0b013e318214332c · Cited by 296
Self-citationNeurodegeneration in multiple sclerosis and neuromyelitis optica
Kawachi, I., & Lassmann, H. (2017) · Journal of Neurology, Neurosurgery & Psychiatry · doi:10.1136/jnnp-2016-313300 · Cited by 283
Metadata
- Authors
- Hinson, S. R., Roemer, S. F., Lucchinetti, C. F., Fryer, J. P., Kryzer, T. J., Chamberlain, J. L., Howe, C. L., Pittock, S. J., & Lennon, V. A.
- Venue
- The Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 2008-10-06
- Volume
- 205
- Issue
- 11
- Pages
- 2473-2481
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- OpenAlex
- W2123936058
- Cited by
- 355
- References
- 30
- FWCI
- 17.48
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Hinson, S. R., Roemer, S. F., Lucchinetti, C. F., Fryer, J. P., Kryzer, T. J., Chamberlain, J. L., Howe, C. L., Pittock, S. J., & Lennon, V. A. (2008). Aquaporin-4–binding autoantibodies in patients with neuromyelitis optica impair glutamate transport by down-regulating EAAT2. The Journal of Experimental Medicine. https://doi.org/10.1084/jem.20081241
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