Mechanisms for lesion localization in neuromyelitis optica spectrum disorders

Neuromyelitis optica spectrum disorders (NMOSD) are severe inflammatory diseases of the central nervous system (CNS), with the presence of aquaporin 4 (AQP4)-specific serum antibodies in the vast majority of patients, and with the presence of myelin oligodendrocyte glycoprotein (MOG)-specific antibodies in approximately 40% of all AQP4-antibody negative NMOSD patients. Despite differences in antigen recognition, the preferred sites of lesions are similar in both groups of patients: They localize to the spinal cord and to the anterior visual pathway including retina, optic nerves, chiasm, and optic tracts, and - to lesser extent - also to certain predilection sites in the brain.

The involvement of T cells in the formation of NMOSD lesions has been challenged for quite some time. However, several recent findings demonstrate the key role of T cells for lesion formation and localization. Studies on the evolution of lesions in the spinal cord of NMOSD patients revealed a striking similarity of early NMOSD lesions with those observed in corresponding T-cell-induced animal models, both in lesion formation and in lesion localization. Studies on retinal abnormalities in NMOSD patients and corresponding animals revealed the importance of T cells for the very early stages of retinal lesions which eventually culminate in damage to Müller cells and to the retinal nerve fiber layer. Finally, a study on cerebrospinal fluid (CSF) barrier pathology demonstrated that NMOSD immunopathology extends beyond perivascular astrocytic foot processes to include the pia, the ependyma, and the choroid plexus, and that diffusion of antibodies from the CSF could further influence lesion formation in NMOSD patients.

The pathological changes observed in AQP4-antibody positive and MOG-antibody positive NMOSD patients are strikingly similar to those found in corresponding animal models, and many mechanisms which determine lesion localization in experimental animals seem to closely reflect the human situation.