Determining the Role of the Cellular Immune Response Against Aquaporin 4 in the Context of Neuromyelitis Optica

Neuromyelitis optica (NMO) is a demyelinating inflammatory disorder of the central nervous system (CNS), which historically is clinically and pathologically defined as the co-occurrence of optic neuritis with myelitis. Thus far, all HLA haplotype analyses in cohorts of NMO patients suggest an association with HLA-DRB103:01. In the majority of patients, IgG against aquaporin-4 (AQP4) can be detected in the serum. AQP4 is expressed in numerous tissues: on the plasma membrane of principal cells and inner medullary collecting duct cells in the kidney, the endothelial cells lining of the gastrointestinal tract, and astrocytic foot processes of astrocytes within the CNS, just to name a few. The role of cellular immune responses against AQP4 in NMO has not been studied. Specifically, linear dominant determinants of AQP4 in the context of HLA-DRB103:01 have not been identified. I hypothesize that CD4+ T cells recognize linear determinants of AQP4 in the context of HLA-DRB1*03:01. I further hypothesize that NMO is co-initiated by AQP4-reactive CD4+ T cells.