title: Cross-immunoreactivity between bacterial aquaporin-Z and human aquaporin-4: potential relevance to neuromyelitis optica.
abstract: 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.
authors.affiliation: Department of Neurological Sciences, Multiple Sclerosis Center, Rush University Medical Center, Chicago, IL 60612, USA.
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Ren
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Tao
authors.initials: T
authors.lastname: Duan
authors.forename: Jilpa
authors.initials: J
authors.lastname: Patel
authors.forename: Thomas
authors.initials: T
authors.lastname: Liggett
authors.forename: Eileah
authors.initials: E
authors.lastname: Loda
authors.forename: Sarang
authors.initials: S
authors.lastname: Brahma
authors.forename: Rajendra
authors.initials: R
authors.lastname: Goswami
authors.forename: Carrie
authors.initials: C
authors.lastname: Grouse
authors.forename: Richard
authors.initials: R
authors.lastname: Byrne
authors.forename: Dusan
authors.initials: D
authors.lastname: Stefoski
authors.forename: Adil
authors.initials: A
authors.lastname: Javed
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Miller
authors.forename: Roumen
authors.initials: R
authors.lastname: Balabanov
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D051401:Aquaporin 4 / Q000235:genetics / Q000378:metabolism*; D020346:Aquaporins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D002478:Cells, Cultured; D003429:Cross Reactions / Q000276:immunology; D003601:Cytotoxicity Tests, Immunologic / Q000379:methods; D029968:Escherichia coli Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D007074:Immunoglobulin G / Q000008:administration & dosage / Q000633:toxicity; D051379:Mice; D008969:Molecular Sequence Data; D009471:Neuromyelitis Optica / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*; D011817:Rabbits; D011994:Recombinant Proteins / Q000276:immunology / Q000378:metabolism; D040681:Structural Homology, Protein
chemical_list: C496030:AQP4 protein, human; D051401:Aquaporin 4; D020346:Aquaporins; D029968:Escherichia coli Proteins; D007074:Immunoglobulin G; D011994:Recombinant Proteins; C106425:aqpZ protein, E coli