Antibodies against the flotillin-1/2 complex in patients with multiple sclerosis

Multiple sclerosis (MS) is a tissue-specific autoimmune disease of the central nervous system in which the antigen(s) remains elusive. Antibodies targeting the flotillin-1/2 (FLOT-1/2) complex have been described in 1-2% of the patients in a recent study. Other candidate antigens as anoctamin-2 (ANO2) or neurofascin-155 (NF155) have been previously described in MS patients, although their clinical relevance remains uncertain. Our study aims to analyse the frequency and clinical relevance of antibodies against NF155, ANO2 and the FLOT-1/2 complex in MS. Serum (n=252) and CSF (n=50) samples from 282 MS patients were included in the study. The control group was composed of 260 serum samples (71 healthy donors and 189 with other neuroinflammatory disorders). Anti-FLOT1/2, anti-ANO2 and anti-NF155 antibodies were tested by cell-based assays using transfected-HEK293 cells. We identified 6 MS patients with antibodies against the FLOT-1/2 complex (2.1%) and 1 MS patient with antibodies against ANO2 (0.35%). All MS patients were negative for anti-NF155 antibodies. Three of the anti-FLOT1/2 positive patients showed anti-FLOT-1/2 positivity in other serum samples extracted at different moments of their disease. IgG subclasses of anti-FLOT-1/2 antibodies were predominantly IgG1 and IgG3. We confirm that antibodies targeting the Flotillin-1/2 complex are present in a subgroup of patients with MS. Further studies are needed to understand the clinical and pathological relevance of anti-FLOT-1/2 autoantibodies in MS.