The etiology of neuromyelitis optica remains unknown, as with other autoimmune diseases. About 10% to 20% of neuromyelitis optica patients have another coexisting autoimmune disease, notably Sjögren disease, myasthenia gravis, systemic lupus erythematosus, and systemic sclerosis. A greater percentage (~50%) have autoantibodies, such as antinuclear antibodies, extractable nuclear antigens, Sjögren syndrome antigen A/B (SSA/SSB), antithyroid thyroglobulin, antithyroid microsomal, antigastroparietal cell, and p-antineutrophil cytoplasmic antibodies (some of which can be disease-causing) (O’Riordan et al 1996; Karussis et al 1998; Wingerchuk et al 1999). It is speculated that neuromyelitis optica occurs as a separate comorbid condition in patients with either preexisting or post-neuromyelitis optica diagnosis of systemic autoimmune disease. However, the evidence for this is sparse, and this remains speculation. Neuromyelitis optica patients can have autoantibodies to paraneoplastic disease markers, such as acetylcholine receptors, glutamate decarboxylase 65, voltage-gated potassium channels, and voltage-gated calcium-channels (Pittock et al 2006c). The association of neuromyelitis optica with a variety of autoantibodies suggests widespread B cell polyclonal activation (Lucchinetti et al 2002).
Neuromyelitis optica has been associated with infections, such as Herpes viruses (human herpesvirus 6, HSV-2, and varicella), Mycoplasma pneumoniae, tuberculosis, Epstein-Barr virus, and HIV (Keefe 1957; Williamson 1975; Khan 1976; Chusid et al 1979; Martin 1982; Silber et al 1990; Ahasan et al 1994; Merelli et al 1997; Blanche et al 2000). It is likely that the various infections associated with neuromyelitis optica produce pathology by triggering B cell dysfunction.
The role of genetic factors in neuromyelitis optica is unknown. There are reports of familial occurrence, but no conclusive evidence exists (McAlpine 1938; Ch’ien et al 1982; Yamakawa et al 2000). There is evidence that neuromyelitis optica is associated with human leukocyte antigen alleles DR1*801, DP1 501, and DPA1 202, but not with DRB1*1501, which is associated with multiple sclerosis (Haase 2001).