Intestinal Bacterial Antigens, Toxin-Induced Pathogenesis and Immune Cross-Reactivity in Neuromyelitis Optica and Multiple Sclerosis

Abstract

Multiple sclerosis (MS) and neuromyelitis optica (NMO) are chronic, potentially disabling, inflammatory autoimmune demyelinating diseases of the central nervous system. Although they share clinical, pathological and immunological features, MS and NMO are now considered two separate entities, and there is evidence that their pathogenesis is different. The latter is now known to be mediated by antibodies against the water channel, aquaporin-4, associated with complement-mediated damage. Environmental factors have been implicated in the pathogenesis of both of these conditions. Among these, infectious factors seem to play a key role. One mechanism whereby infection triggers autoimmunity is molecular mimicry resulting in immune cross-reactivity between infectious antigens and autoantigens. Recently, a number of studies have pointed to an immunological cross-reactivity between intestinal bacteria and aquaporin-4, providing a potential pathophysiological mechanism for NMO. The bacteria involved were Clostridium and E. coli. The immune cross-reactivity is not restricted to antibodies but also involves T cells against aquaporin-4 that also recognises clostridium epitopes. Interestingly, Clostridium perfringens and its immunological or direct neurotoxic effects (e.g. disruption of the blood-brain barrier) have also been implicated in MS. This chapter reviews the relevant data regarding the role of these gut bacteria and the immune responses they trigger in MS and NMO with some insights into the pathogenesis of these inflammatory demyelinating diseases.