Ren Z, Wang Y, Duan T, Patel J, Liggett T, Loda E, Brahma S, Goswami R, Grouse C, Byrne R, Stefoski D, Javed A, Miller SD, Balabanov R.
Source: Department of Neurological Sciences, Multiple Sclerosis Center, Rush University Medical Center, Chicago, IL 60612, USA.
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.
PMID: 23008451 [PubMed – indexed for MEDLINE]
J Immunol. 2012 Nov 1;189(9):4602-11. doi: 10.4049/jimmunol.1200486. Epub 2012 Sep 24