{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T20:20:09Z","timestamp":1790281209320,"version":"4.1.0"},"reference-count":51,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2012,11,1]],"date-time":"2012-11-01T00:00:00Z","timestamp":1351728000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2012,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Neuromyelitis optica (NMO) is a chronic inflammatory disease of the CNS that is mediated, in part, by a self-reactive Ab against the astrocyte aquaporin-4 protein. In the current study, we examined the possibility and the biological significance of cross-immunoreactivity between bacterial aquaporin-Z and human aquaporin-4 proteins. Sequence-alignment analysis of these proteins revealed several regions of significant structural homology. Some of the homologous regions were also found to overlap with important immune and disease-relevant epitopes. Cross-immunoreactivity between aquaporin-Z and aquaporin-4 was investigated and ascertained in multiple immune-based assays using sera from patients with neuromyelitis optica, immune mouse serum, and Abs raised against aquaporin-Z. The biological significance of this phenomenon was established in series of experiments demonstrating that induction of an immune response against aquaporin-Z or its homologous regions can also trigger an autoimmune reaction against aquaporin-4 and inflammation of the CNS. Our study indicates that the autoimmune response against aquaporin-4 in neuromyelitis optica may be triggered by infection-induced cross-immunoreactivity and presents a new perspective on the pathogenesis of this disease.<\/jats:p>","DOI":"10.4049\/jimmunol.1200486","type":"journal-article","created":{"date-parts":[[2012,9,25]],"date-time":"2012-09-25T16:49:48Z","timestamp":1348591788000},"page":"4602-4611","source":"Crossref","is-referenced-by-count":42,"title":["Cross-Immunoreactivity between Bacterial Aquaporin-Z and Human Aquaporin-4: Potential Relevance to Neuromyelitis Optica"],"prefix":"10.1093","volume":"189","author":[{"given":"Zhihua","family":"Ren","sequence":"first","affiliation":[{"name":"Department of Neurological Sciences, Multiple Sclerosis Center, Rush University Medical Center , Chicago, IL 60612"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurological Sciences, Multiple Sclerosis Center, Rush University Medical Center , Chicago, IL 60612"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Duan","sequence":"additional","affiliation":[{"name":"Department of Neurological Sciences, Multiple Sclerosis Center, Rush University Medical Center , Chicago, IL 60612"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jilpa","family":"Patel","sequence":"additional","affiliation":[{"name":"Department of Neurological Sciences, Multiple Sclerosis Center, Rush University Medical Center , Chicago, IL 60612"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Liggett","sequence":"additional","affiliation":[{"name":"Department of Neurological Sciences, Multiple Sclerosis Center, Rush University Medical Center , Chicago, IL 60612"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eileah","family":"Loda","sequence":"additional","affiliation":[{"name":"Department of Neurological Sciences, Multiple Sclerosis Center, Rush University Medical Center , Chicago, IL 60612"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarang","family":"Brahma","sequence":"additional","affiliation":[{"name":"Department of Neurological Sciences, Multiple Sclerosis Center, Rush University Medical Center , Chicago, IL 60612"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajendra","family":"Goswami","sequence":"additional","affiliation":[{"name":"Department of Neurological Sciences, Multiple Sclerosis Center, Rush University Medical Center , Chicago, IL 60612"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carrie","family":"Grouse","sequence":"additional","affiliation":[{"name":"Department of Neurological Sciences, Multiple Sclerosis Center, Rush University Medical Center , Chicago, IL 60612"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Byrne","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Rush University Medical Center , Chicago, IL 60612"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dusan","family":"Stefoski","sequence":"additional","affiliation":[{"name":"Department of Neurological Sciences, Multiple Sclerosis Center, Rush University Medical Center , Chicago, IL 60612"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adil","family":"Javed","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Chicago , Chicago, IL 60637"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen D","family":"Miller","sequence":"additional","affiliation":[{"name":"Department of Microbiology-Immunology, Northwestern University Medical School , Chicago, IL 60611"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roumen","family":"Balabanov","sequence":"additional","affiliation":[{"name":"Department of Neurological Sciences, Multiple Sclerosis Center, Rush University Medical Center , Chicago, IL 60612"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2012,11,1]]},"reference":[{"key":"2025032409321642400_r1","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1016\/S1474-4422(07)70216-8","article-title":"The spectrum of neuromyelitis optica","volume":"6","author":"Wingerchuk","year":"2007","journal-title":"Lancet Neurol."},{"key":"2025032409321642400_r2","doi-asserted-by":"crossref","first-page":"1450","DOI":"10.1093\/brain\/awf151","article-title":"A role for humoral mechanisms in the pathogenesis of Devic\u2019s neuromyelitis optica","volume":"125","author":"Lucchinetti","year":"2002","journal-title":"Brain"},{"key":"2025032409321642400_r3","doi-asserted-by":"crossref","first-page":"2106","DOI":"10.1016\/S0140-6736(04)17551-X","article-title":"A serum autoantibody marker of neuromyelitis optica: distinction from multiple sclerosis","volume":"364","author":"Lennon","year":"2004","journal-title":"Lancet"},{"key":"2025032409321642400_r4","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1001\/archneurol.2007.17","article-title":"Neuromyelitis optica and non organ-specific autoimmunity","volume":"65","author":"Pittock","year":"2008","journal-title":"Arch. Neurol."},{"key":"2025032409321642400_r5","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1177\/1352458508088941","article-title":"Minor salivary gland inflammation in Devic\u2019s disease and longitudinally extensive myelitis","volume":"14","author":"Javed","year":"2008","journal-title":"Mult. Scler."},{"key":"2025032409321642400_r6","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1016\/j.jaut.2009.09.013","article-title":"The clinical spectrum and immunobiology of parainfectious neuromyelitis optica (Devic) syndromes","volume":"34","author":"Sellner","year":"2010","journal-title":"J. Autoimmun."},{"key":"2025032409321642400_r7","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1513\/pats.200510-109JH","article-title":"The aquaporin water channels","volume":"3","author":"Agre","year":"2006","journal-title":"Proc. Am. Thorac. Soc."},{"key":"2025032409321642400_r8","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1080\/09687680701446965","article-title":"The structural basis of water permeation and proton exclusion in aquaporins","volume":"24","author":"Fu","year":"2007","journal-title":"Mol. Membr. Biol."},{"key":"2025032409321642400_r9","doi-asserted-by":"crossref","first-page":"1707","DOI":"10.1242\/jeb.024125","article-title":"Aquaporins: translating bench research to human disease","volume":"212","author":"Verkman","year":"2009","journal-title":"J. Exp. Biol."},{"key":"2025032409321642400_r10","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1084\/jem.20050304","article-title":"IgG marker of optic-spinal multiple sclerosis binds to the aquaporin-4 water channel","volume":"202","author":"Lennon","year":"2005","journal-title":"J. Exp. Med."},{"key":"2025032409321642400_r11","doi-asserted-by":"crossref","first-page":"2221","DOI":"10.1212\/01.WNL.0000289761.64862.ce","article-title":"Pathogenic potential of IgG binding to water channel extracellular domain in neuromyelitis optica","volume":"69","author":"Hinson","year":"2007","journal-title":"Neurology"},{"key":"2025032409321642400_r12","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1002\/ana.21802","article-title":"Intrathecal pathogenic anti-aquaporin-4 antibodies in early neuromyelitis optica","volume":"66","author":"Bennett","year":"2009","journal-title":"Ann. Neurol."},{"key":"2025032409321642400_r13","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1111\/j.1749-6632.2009.04871.x","article-title":"Effector functions of antiaquaporin-4 autoantibodies in neuromyelitis optica","volume":"1173","author":"Cayrol","year":"2009","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"2025032409321642400_r14","doi-asserted-by":"crossref","first-page":"1194","DOI":"10.1093\/brain\/awl371","article-title":"Pattern-specific loss of aquaporin-4 immunoreactivity distinguishes neuromyelitis optica from multiple sclerosis","volume":"130","author":"Roemer","year":"2007","journal-title":"Brain"},{"key":"2025032409321642400_r15","doi-asserted-by":"crossref","first-page":"1224","DOI":"10.1093\/brain\/awm047","article-title":"Loss of aquaporin 4 in lesions of neuromyelitis optica: distinction from multiple sclerosis","volume":"130","author":"Misu","year":"2007","journal-title":"Brain"},{"key":"2025032409321642400_r16","doi-asserted-by":"crossref","first-page":"964","DOI":"10.1001\/archneur.63.7.964","article-title":"Neuromyelitis optica brain lesions localized at sites of high aquaporin 4 expression","volume":"63","author":"Pittock","year":"2006","journal-title":"Arch. Neurol."},{"key":"2025032409321642400_r17","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.jneuroim.2009.07.014","article-title":"Cytotoxic effect of neuromyelitis optica antibody (NMO-IgG) to astrocytes: an in vitro study","volume":"215","author":"Sabater","year":"2009","journal-title":"J. Neuroimmunol."},{"key":"2025032409321642400_r18","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.jneuroim.2009.04.001","article-title":"Identification of binding sites for anti-aquaporin 4 antibodies in patients with neuromyelitis optica","volume":"211","author":"Tani","year":"2009","journal-title":"J. Neuroimmunol."},{"key":"2025032409321642400_r19","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2012.07.008","article-title":"Astrocytic autoantibody of neuromyelitis optica (NMO-IgG) binds to aquaporin-4 extracellular loops, monomers, tetramers and high order arrays","volume-title":"J. Autoimmun.","author":"Iorio","year":"2012"},{"key":"2025032409321642400_r20","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.tins.2007.11.003","article-title":"Water movements in the brain: role of aquaporins","volume":"31","author":"Tait","year":"2008","journal-title":"Trends Neurosci."},{"key":"2025032409321642400_r21","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1186\/1471-2202-10-94","article-title":"Greatly attenuated experimental autoimmune encephalomyelitis in aquaporin-4 knockout mice","volume":"10","author":"Li","year":"2009","journal-title":"BMC Neurosci."},{"key":"2025032409321642400_r22","doi-asserted-by":"crossref","first-page":"2473","DOI":"10.1084\/jem.20081241","article-title":"Aquaporin-4-binding autoantibodies in patients with neuromyelitis optica impair glutamate transport by down-regulating EAAT2","volume":"205","author":"Hinson","year":"2008","journal-title":"J. Exp. Med."},{"key":"2025032409321642400_r23","doi-asserted-by":"crossref","first-page":"5730","DOI":"10.4049\/jimmunol.181.8.5730","article-title":"Functional consequences of neuromyelitis optica-IgG astrocyte interactions on blood-brain barrier permeability and granulocyte recruitment","volume":"181","author":"Vincent","year":"2008","journal-title":"J. Immunol."},{"key":"2025032409321642400_r24","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1006\/jmbi.1999.3032","article-title":"Functional reconstitution and characterization of AqpZ, the E. coli water channel protein","volume":"291","author":"Borgnia","year":"1999","journal-title":"J. Mol. Biol."},{"key":"2025032409321642400_r25","doi-asserted-by":"crossref","first-page":"29063","DOI":"10.1074\/jbc.270.49.29063","article-title":"Molecular cloning and characterization of AqpZ, a water channel from Escherichia coli","volume":"270","author":"Calamita","year":"1995","journal-title":"J. Biol. Chem."},{"key":"2025032409321642400_r26","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1128\/JB.188.2.820-822.2006","article-title":"AqpZ-mediated water permeability in Escherichia coli measured by stopped-flow spectroscopy","volume":"188","author":"Mallo","year":"2006","journal-title":"J. Bacteriol."},{"key":"2025032409321642400_r27","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1126\/science.2414848","article-title":"Amino acid homology between the encephalitogenic site of myelin basic protein and virus: mechanism for autoimmunity","volume":"230","author":"Fujinami","year":"1985","journal-title":"Science"},{"key":"2025032409321642400_r28","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/S0966-842X(03)00006-4","article-title":"Mimicking the way to autoimmunity: an evolving theory of sequence and structural homology","volume":"11","author":"Kohm","year":"2003","journal-title":"Trends Microbiol."},{"key":"2025032409321642400_r29","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1097\/WCO.0b013e32832b4c8d","article-title":"Epstein-Barr virus and multiple sclerosis","volume":"22","author":"Salvetti","year":"2009","journal-title":"Curr. Opin. Neurol."},{"key":"2025032409321642400_r30","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1080\/08916930500484757","article-title":"Streptococcal mimicry and antibody-mediated cell signaling in the pathogenesis of Sydenham\u2019s chorea","volume":"39","author":"Kirvan","year":"2006","journal-title":"Autoimmunity"},{"key":"2025032409321642400_r31","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1002\/1531-8249(200010)48:4<624::AID-ANA9>3.0.CO;2-O","article-title":"Axonal Guillain-Barr\u00e9 syndrome: relation to anti-ganglioside antibodies and Campylobacter jejuni infection in Japan","volume":"48","author":"Ogawara","year":"2000","journal-title":"Ann. Neurol."},{"key":"2025032409321642400_r32","doi-asserted-by":"crossref","first-page":"1485","DOI":"10.1212\/01.wnl.0000216139.44259.74","article-title":"Revised diagnostic criteria for neuromyelitis optica","volume":"66","author":"Wingerchuk","year":"2006","journal-title":"Neurology"},{"key":"2025032409321642400_r33","doi-asserted-by":"crossref","first-page":"2013","DOI":"10.1523\/JNEUROSCI.4689-06.2007","article-title":"Interferon-gamma-oligodendrocyte interactions in the regulation of experimental autoimmune encephalomyelitis","volume":"27","author":"Balabanov","year":"2007","journal-title":"J. Neurosci."},{"key":"2025032409321642400_r34","first-page":"1070","article-title":"New latex bead agglutination assay for differential diagnosis of cattle infected with Mycobacterium bovis and Mycobacterium avium subsp. paratuberculosis","volume":"11","author":"Koo","year":"2004","journal-title":"Clin. Diagn. Lab. Immunol."},{"key":"2025032409321642400_r35","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1002\/glia.20912","article-title":"STAT1\/IRF-1 signaling pathway mediates the injurious effect of interferon-gamma on oligodendrocyte progenitor cells","volume":"58","author":"Wang","year":"2010","journal-title":"Glia"},{"key":"2025032409321642400_r36","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.jneuroim.2011.01.001","article-title":"IRF-1 signaling in central nervous system glial cells regulates inflammatory demyelination","volume":"233","author":"Ren","year":"2011","journal-title":"J. Neuroimmunol."},{"key":"2025032409321642400_r37","doi-asserted-by":"crossref","first-page":"7016","DOI":"10.1073\/pnas.88.16.7016","article-title":"Gamma-interferon promotes proliferation of adult human astrocytes in vitro and reactive gliosis in the adult mouse brain in vivo","volume":"88","author":"Yong","year":"1991","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025032409321642400_r38","doi-asserted-by":"crossref","first-page":"8329","DOI":"10.1523\/JNEUROSCI.1028-11.2011","article-title":"Overexpression of the dominant-negative form of interferon regulatory factor 1 in oligodendrocytes protects against experimental autoimmune encephalomyelitis","volume":"31","author":"Ren","year":"2011","journal-title":"J. Neurosci."},{"key":"2025032409321642400_r39","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1007\/s00401-011-0824-0","article-title":"Pathogenic T cell responses against aquaporin 4","volume":"122","author":"Pohl","year":"2011","journal-title":"Acta Neuropathol."},{"key":"2025032409321642400_r40","doi-asserted-by":"crossref","first-page":"e15050","DOI":"10.1371\/journal.pone.0015050","article-title":"Immunodominant T cell determinants of aquaporin-4, the autoantigen associated with neuromyelitis optica","volume":"5","author":"Nelson","year":"2010","journal-title":"PLoS ONE"},{"key":"2025032409321642400_r41","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1093\/intimm\/dxr056","article-title":"Increased T-cell immunity against aquaporin-4 and proteolipid protein in neuromyelitis optica","volume":"23","author":"Matsuya","year":"2011","journal-title":"Int. Immunol."},{"key":"2025032409321642400_r42","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1093\/brain\/awp309","article-title":"Intra-cerebral injection of neuromyelitis optica immunoglobulin G and human complement produces neuromyelitis optica lesions in mice","volume":"133","author":"Saadoun","year":"2010","journal-title":"Brain"},{"key":"2025032409321642400_r43","doi-asserted-by":"crossref","first-page":"1372","DOI":"10.1016\/j.jocn.2010.02.023","article-title":"Anti-tuberculosis treatment for Devic\u2019s neuromyelitis optica","volume":"17","author":"Feng","year":"2010","journal-title":"J. Clin. Neurosci."},{"key":"2025032409321642400_r44","doi-asserted-by":"crossref","first-page":"1411","DOI":"10.1177\/1352458509348961","article-title":"Association of anti-Helicobacter pylori neutrophil-activating protein antibody response with anti-aquaporin-4 autoimmunity in Japanese patients with multiple sclerosis and neuromyelitis optica","volume":"15","author":"Li","year":"2009","journal-title":"Mult. Scler."},{"key":"2025032409321642400_r45","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1136\/jnnp.73.4.429","article-title":"Optic neuromyelitis syndrome in Brazilian patients","volume":"73","author":"Papais-Alvarenga","year":"2002","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"2025032409321642400_r46","doi-asserted-by":"crossref","first-page":"776","DOI":"10.5483\/BMBRep.2009.42.12.776","article-title":"Th17 responses and host defense against microorganisms: an overview","volume":"42","author":"van de Veerdonk","year":"2009","journal-title":"BMB Rep."},{"key":"2025032409321642400_r47","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1016\/j.it.2011.03.008","article-title":"Interferon-\u03b2 exacerbates Th17-mediated inflammatory disease","volume":"32","author":"Axtell","year":"2011","journal-title":"Trends Immunol."},{"key":"2025032409321642400_r48","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.jneuroim.2011.03.009","article-title":"Increased memory Th17 cells in patients with neuromyelitis optica and multiple sclerosis","volume":"234","author":"Li","year":"2011","journal-title":"J. Neuroimmunol."},{"key":"2025032409321642400_r49","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1002\/ana.23651","article-title":"Aquaporin 4-specific T cells in neuromyelitis optica exhibit a Th17 bias and recognize Clostridium ABC transporter","volume":"72","author":"Varrin-Doyer","year":"2012","journal-title":"Ann. Neurol."},{"key":"2025032409321642400_r50","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1177\/1352458508102085","article-title":"Is neuromyelitis optica associated with human leukocyte antigen?","volume":"15","author":"Z\u00e9phir","year":"2009","journal-title":"Mult. Scler."},{"key":"2025032409321642400_r51","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.jns.2006.06.011","article-title":"Characterization of the T cell receptor repertoire in the Japanese neuromyelitis optica: T cell activity is up-regulated compared to multiple sclerosis","volume":"249","author":"Warabi","year":"2006","journal-title":"J. Neurol. Sci."}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/189\/9\/4602\/62484874\/1200486.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/189\/9\/4602\/62484874\/1200486.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,27]],"date-time":"2025-03-27T08:10:06Z","timestamp":1743063006000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/189\/9\/4602\/7997773"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,11,1]]},"references-count":51,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2012,11,1]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.1200486","relation":{},"ISSN":["0022-1767","1550-6606"],"issn-type":[{"value":"0022-1767","type":"print"},{"value":"1550-6606","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2012,11]]},"published":{"date-parts":[[2012,11,1]]}}}