FIGURE 1.

Strategy to define the role of autoantibodies in brain disease: the example of aquaporin 4 (AQP‐4) antibody‐associated neuromyelitis optica spectrum disorders (NMOSD). In the first step an inflammatory demyelinating disease with a clinical phenotype of optico‐spinal multiple sclerosis or neuromyelitis optica (NMO) has been identified to be associated with extensive antibody (a) and complement deposition in the lesions (b) [10]. This stimulated the search for autoantibodies in the patient sera, which revealed antibody binding to perivascular astrocyte processes (c) [11] and the identification of the target antigen as AQP‐4 [12]. These patient derived autoantibodies induced pathological alterations in the rodent nervous system after transfer into animals with T‐cell‐mediated brain inflammation (d), which were closely similar to those seen in NMO patients (e) [13, 14]. In parallel, a reliable paraclinical test was developed, which detects AQP‐4 antibodies in transfected cell lines (f). Using this paraclinical test for diagnosis it was possible to elucidate the clinical phenotype of NMOSD (g) [16]. EAE: experimental autoimmune encephalomyelitis [Colour figure can be viewed at wileyonlinelibrary.com]