BMPS were generated from human iPSC generated from fibroblasts using EBV-based vectors; iPSCs colonies were differentiated to generate aggregates of neuronal and glial progenitor cells on culture. Immunohistochemistry was performed on BMPS incubated with primary antibodies to surface neuronal and glial proteins, or human serum/CSF from patients with autoimmune CNS disorders and healthy controls, combined with intracellular markers of neurons and glial cells. For detection, secondary fluorescent antibodies were used.

BMPS showed expression of neuronal and glial antigens targeted in NMDA, LE encephalitis, NMO, and MOG. NR1 and LGI1 expression was observed only in neuronal cells. AQP4 and MOG expression was observed only in glial cells. Patient serum and CSF from patients suffering from NMDA (n=4) and LE (n=2) encephalitis bound to BMPS neuronal cells, while serum from patients suffering from NMO (n=2) and MOG (n=2) bound to BMPS glial cells.  Serum/CSF from healthy controls (n=10) did not bind to BMPS neuronal or glial cells.

Thirteen patient’s sera/CSF with presumed autoimmune CNS disorder but sero-negative by conventional assays were screened with BMPS; eight bound to antigens present in neuronal and/or glial cells in different staining patterns. Six demonstrated extracellular binding and two intracellular binding.

Since human BMPs may express human-specific antigens that are not present on rodent cells, they could be an additional diagnostic and research tool for autoimmune CNS disorders.