To analyse autoantibodies against the flotillin-1/2 complex (Flot-Ab) in patients with otherwise seronegative inflammatory conditions of the central nervous system (CNS); to describe the characteristics of Flot-Ab seropositive cases.

Flotillin 1 and flotillin 2 have been recently identified as target antigens in some patients with multiple sclerosis. However, only 14 cases have been reported up to now, in one single report.

Sera and, when available, CSF sample of patients with well-characterised idiopathic inflammatory CNS disorders referred to the Neurology Unit, University Hospital of Verona, between March 2014 and May 2018 were analysed for Flot-Ab using a cell-based assay (Euroimmun, Lübeck). Immunohistochemistry on rat brain was performed in case of Flot-Ab positivity. In the second part of the study, subjects referred to the laboratory of Neuropathology, University of Vienna, showing similar peculiar immunohistochemical pattern were reviewed and selected for Flot-Ab analysis.

The analysed cohort consisted of patients with multiple sclerosis (N=43), clinically isolated syndrome (N=15), idiopathic optic neuritis (N=84), acute myelitis (N=42), neuromyelitis optica (N=4), and both optic neuritis and myelitis (N=8). Among these, one patient with progressive multiple sclerosis resulted positive for both serum and CSF Flot-Ab. This patient showed a peculiar fine-granular staining in hippocampus and cerebellum of rat brain on immunohistochemistry. Two additional cases then selected based on the immunohistochemical pattern resulted also positive for Flot-Ab. One of these cases had a final diagnosis of multiple sclerosis (only serum available for Flot-Ab analysis), while in the other (positive in both serum and CSF) the differential diagnosis between a vascular and a demyelinating disorder is still debated.