The brain as immunoprecipitator of serum autoantibodies against N-Methyl-D-aspartate receptor subunit NR1

Autoantibodies (AB) against N-methyl-D-aspartate receptor subunit NR1 (NMDAR1) are highly seroprevalent in health and disease. Symptomatic relevance may arise upon compromised blood–brain barrier (BBB). However, it remained unknown whether circulating NMDAR1 AB appear in the cerebrospinal fluid (CSF). Of n = 271 subjects with CSF–serum pairs, 26 were NMDAR1 AB seropositive, but only 1 was CSF positive. Contrariwise, tetanus AB (non–brain-binding) were present in serum and CSF of all subjects, with CSF levels higher upon BBB dysfunction. Translational mouse experiments proved the hypothesis that the brain acts as an ‘immunoprecipitator’; simultaneous injection of NMDAR1 AB and the non–brain-binding green fluorescent protein AB resulted in high detectability of the former in brain and the latter in CSF.