Research: are bacteria a cause of NMO

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.