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Article: Aquaporin-4 autoantibodies cause asymptomatic aquaporin-4 loss and activate astrocytes in mouse

TitleAquaporin-4 autoantibodies cause asymptomatic aquaporin-4 loss and activate astrocytes in mouse
Authors
KeywordsAquaporin-4 autoantibodies
Aquaporin-4 water channel
Astrocyte activation
Complement activation
Mouse
Neuromyelitis optica
Issue Date2012
PublisherElsevier BV. The Journal's web site is located at http://www.elsevier.com/locate/jneuroim
Citation
Journal Of Neuroimmunology, 2012, v. 245 n. 1-2, p. 32-38 How to Cite?
AbstractBackground: Neuromyelitis optica (NMO) is a central nervous system inflammatory demyelinating disorder. Up to 90% of patients are seropositive for aquaporin-4 autoantibodies (AQP4 Ab). The pathogenetic mechanisms underlying clinical onset and relapse of NMO are uncertain. Objective: Study the pathogenicity of AQP4 Ab in the absence of complement activation. Methods: Female C57BL/6N mice (human IgG cannot activate mouse complements) pretreated with complete Freund's adjuvant (CFA, day 0) and pertussis toxin (PTx, day 0 and day 2) were transferred with IgG isolated from serum of healthy subjects or NMO patients (AQP4 Ab-positive or negative) intraperitoneally (day 7-9). Mice were observed for signs of experimental autoimmune encephalomyelitis (EAE) by standard 6-grade EAE scores. Spinal cord was obtained at day 11 for immunohistochemistry. Results: None of the mice had clinical signs of encephalomyelitis, inflammatory cells infiltration or demyelination of spinal cord. CFA and PTx induce BBB breakdown evidenced by leakage of human IgG into cord parenchyma. Patchy areas of AQP4 loss were observed in spinal cord of mice transferred with IgG from AQP4 Ab-positive NMO patients but not in mice transferred with IgG from AQP4 Ab-negative NMO patients or healthy subjects; but there was no loss of glial fibrillary acidic protein immunoreactivity in all mice. Markedly increased proliferation of astrocytic processes suggestive of astrocytic activation was observed in mice transferred with IgG from AQP4 Ab-positive patients. Conclusion: AQP4 Ab cause asymptomatic AQP4 loss and astrocytic activation but not myelitis, demyelination or astrocytic cytotoxicity in spinal cord of mouse in the absence of complement activation. © 2012 Elsevier B.V.
Persistent Identifierhttp://hdl.handle.net/10722/148833
ISSN
2015 Impact Factor: 2.536
2015 SCImago Journal Rankings: 1.165
ISI Accession Number ID
Funding AgencyGrant Number
LKS Faculty of Medicine, the University of Hong Kong
Bayer HealthCare
Merck Pharmaceutical Limited
Funding Information:

This study is supported by Seed Funding for Basic Research of the LKS Faculty of Medicine, the University of Hong Kong.

References

 

DC FieldValueLanguage
dc.contributor.authorChan, KHen_HK
dc.contributor.authorZhang, Ren_HK
dc.contributor.authorKwan, JSCen_HK
dc.contributor.authorGuo, VYen_HK
dc.contributor.authorHo, PWLen_HK
dc.contributor.authorHo, JWMen_HK
dc.contributor.authorChu, ACYen_HK
dc.date.accessioned2012-06-08T02:36:57Z-
dc.date.available2012-06-08T02:36:57Z-
dc.date.issued2012en_HK
dc.identifier.citationJournal Of Neuroimmunology, 2012, v. 245 n. 1-2, p. 32-38en_HK
dc.identifier.issn0165-5728en_HK
dc.identifier.urihttp://hdl.handle.net/10722/148833-
dc.description.abstractBackground: Neuromyelitis optica (NMO) is a central nervous system inflammatory demyelinating disorder. Up to 90% of patients are seropositive for aquaporin-4 autoantibodies (AQP4 Ab). The pathogenetic mechanisms underlying clinical onset and relapse of NMO are uncertain. Objective: Study the pathogenicity of AQP4 Ab in the absence of complement activation. Methods: Female C57BL/6N mice (human IgG cannot activate mouse complements) pretreated with complete Freund's adjuvant (CFA, day 0) and pertussis toxin (PTx, day 0 and day 2) were transferred with IgG isolated from serum of healthy subjects or NMO patients (AQP4 Ab-positive or negative) intraperitoneally (day 7-9). Mice were observed for signs of experimental autoimmune encephalomyelitis (EAE) by standard 6-grade EAE scores. Spinal cord was obtained at day 11 for immunohistochemistry. Results: None of the mice had clinical signs of encephalomyelitis, inflammatory cells infiltration or demyelination of spinal cord. CFA and PTx induce BBB breakdown evidenced by leakage of human IgG into cord parenchyma. Patchy areas of AQP4 loss were observed in spinal cord of mice transferred with IgG from AQP4 Ab-positive NMO patients but not in mice transferred with IgG from AQP4 Ab-negative NMO patients or healthy subjects; but there was no loss of glial fibrillary acidic protein immunoreactivity in all mice. Markedly increased proliferation of astrocytic processes suggestive of astrocytic activation was observed in mice transferred with IgG from AQP4 Ab-positive patients. Conclusion: AQP4 Ab cause asymptomatic AQP4 loss and astrocytic activation but not myelitis, demyelination or astrocytic cytotoxicity in spinal cord of mouse in the absence of complement activation. © 2012 Elsevier B.V.en_HK
dc.languageeng-
dc.publisherElsevier BV. The Journal's web site is located at http://www.elsevier.com/locate/jneuroimen_HK
dc.relation.ispartofJournal of Neuroimmunologyen_HK
dc.subjectAquaporin-4 autoantibodiesen_HK
dc.subjectAquaporin-4 water channelen_HK
dc.subjectAstrocyte activationen_HK
dc.subjectComplement activationen_HK
dc.subjectMouseen_HK
dc.subjectNeuromyelitis opticaen_HK
dc.subject.meshAquaporin 4 - antagonists and inhibitors - deficiency - genetics - immunology-
dc.subject.meshAstrocytes - immunology - metabolism - pathology-
dc.subject.meshAutoantibodies - toxicity-
dc.subject.meshDemyelinating Diseases - immunology - metabolism - pathology-
dc.subject.meshNeuromyelitis Optica - immunology - metabolism - pathology-
dc.titleAquaporin-4 autoantibodies cause asymptomatic aquaporin-4 loss and activate astrocytes in mouseen_HK
dc.typeArticleen_HK
dc.identifier.emailHo, PWL: hwl2002@hku.hken_HK
dc.identifier.emailChu, ACY: bcccy@hkucc.hku.hken_HK
dc.identifier.authorityHo, PWL=rp00259en_HK
dc.identifier.authorityChu, ACY=rp00505en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1016/j.jneuroim.2012.02.001en_HK
dc.identifier.pmid22394609-
dc.identifier.scopuseid_2-s2.0-84859646628en_HK
dc.identifier.hkuros199853-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-84859646628&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume245en_HK
dc.identifier.issue1-2en_HK
dc.identifier.spage32en_HK
dc.identifier.epage38en_HK
dc.identifier.isiWOS:000303908100005-
dc.publisher.placeNetherlandsen_HK
dc.identifier.scopusauthoridChan, KH=36493922700en_HK
dc.identifier.scopusauthoridZhang, R=35498428600en_HK
dc.identifier.scopusauthoridKwan, JSC=36479956300en_HK
dc.identifier.scopusauthoridGuo, VY=55043533600en_HK
dc.identifier.scopusauthoridHo, PWL=25027612100en_HK
dc.identifier.scopusauthoridHo, JWM=8685214100en_HK
dc.identifier.scopusauthoridChu, ACY=24343085700en_HK
dc.identifier.citeulike10425040-

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