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Life sciences · Journal article
Annals of Clinical and Translational Neurology · October 4, 2026
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ABSTRACT We characterize copine‐4 (CPNE4)‐IgG and report clinical associations. Among 844 samples with unclassified neural IgGs identified by mouse‐brain indirect immunofluorescence assay over 2 years, 5 samples (serum, 3; CSF, 2) from 3 patients produced a distinctive cerebrum‐restricted synaptic pattern. Protein microarray disclosed CPNE4 “top hit” in those 3 patients; specificity was confirmed by 3 CPNE4‐specific assays (confocal IFA, cell‐based, and western blot). Median onset age was 67 years (range 60–68); all had encephalitis: a brainstem syndrome during immune checkpoint inhibitor therapy for lung cancer (2) and anti‐NMDA‐receptor encephalitis accompanied by neuroectoderm‐lineage cancer (1). To date, CPNE4‐IgG has paraneoplastic encephalitis significance.