Figure 4.

Brain-directed autoantibodies in ICI-treated cancer patients with irAE-n. (A, B) Cell-based assays of fixed recombinant HEK293-cells (original magnification x 200) expressing single neuronal antigens showing anti-Zic4 autoantibodies (1:100 dilution; A) and anti-GABA_BR autoantibodies (1:10, B) in a patient with small cell lung cancer and Guillain-Barré syndrome (GBS) after pembrolizumab treatment. However, anti-ganglioside autoantibodies, which are associated with GBS, were tested negative during clinical routine. (C) Tissue-based assay using indirect immunofluorescence screening on monkey cerebellum sections (original magnification x 200) showing anti-GFAP autoantibodies (1:100 dilution) in a melanoma patient with encephalitis after treatment with ipilimumab and nivolumab. GABA_BR, gamma-aminobutyric-acid B receptor; GFAP, glial fibrillary acidic protein; ICI, immune checkpoint inhibitor; irAE-n, neurological immune related adverse event; Zic4, zinc finger 4.