Methods included clinical characterization, indirect immunofluorescence, immunoprecipitation, mass spectrometry, immunoblots of wild-type and
synapsin I/II/III knockout mice, and cell-based assays with
synapsin Ia, Ib, IIa, and IIb plasmids.
RESULTS: A 69-year-old man presented with
confusion, disorientation,
seizures, and left hippocampal hyperintensities on MRI. CSF examinations revealed an intrathecal
IgA and
IgG synthesis. Except for
IgG antibodies to
voltage-gated potassium channels in CSF, screening for known neuronal
autoantibodies in serum and CSF was negative. However, indirect immunofluorescence using the patient's CSF showed binding of
IgA to mouse hippocampus, amygdala, and cerebellum. Immunoprecipitation with CSF
IgA followed by mass spectrometry identified
synapsin as autoantigenic target. Knockout tissues and cell-based assays confirmed that
IgA and
IgG in the patient's CSF and serum reacted with
synapsin Ia, Ib, and IIa. Calculation of antibody indices proved intrathecal synthesis of anti-
synapsin IgA and
IgG. The patient responded clinically to
immunotherapy but developed left hippocampal
atrophy. CSF
IgA or
IgG of the patient did not bind to live, unfixed, and nonpermeabilized mouse hippocampal neurons, compatible with
synapsin being an intracellular
antigen.
CONCLUSIONS: