Cross-immunoreactivity between bacterial aquaporin-Z and human aquaporin-4: Potential relevance to neuromyelitis optica

Zhihua Ren, Yan Wang, Tao Duan, Jilpa Patel, Thomas Liggett, Eileah Loda, Sarang Brahma, Rajendra Goswami, Carrie Grouse, Richard Byrne, Dusan Stefoski, Adil Javed, Stephen D. Miller, Roumen Balabanov*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)4602-4611
Number of pages10
JournalJournal of Immunology
Volume189
Issue number9
DOIs
StatePublished - Nov 1 2012

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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