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. Cross-Immunoreactivity between Bacterial Aquaporin-Z and Human Aquaporin-4: Potential Relevance to Neuromyelitis Optica.J Immunol. 2012. [Epub ahead of print]
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 (AQ4) 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.
We think that many autoimmune diseases may be triggered by a cross-reactive immune response that is initiated by a bacteria/virus but the anti-bacterial immune response may be inadvertently be directed against a brain protein. In this study they report that an immune response to a bacterial protein can cross react with a water channel on astrocytes and this causes NMO a demyelinating disease of mainly the optic nerve and spinal cord. A few cross-reactive responses have been reported to occur for MS, such as with EBV. One way to look for a disease triggering role is to do something about the infection and hopefully the disease will be affected. This is what the Charcot project intends to do.