Cerebellar syndrome associated with adaptor protein 3B2-IgG following pembrolizumab treatment for metastatic adenocarcinoma of the lung

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Immune checkpoint inhibitors (ICIs) have transformed cancer therapy but are associated with a broad spectrum of neurological immune-related complications. These include paraneoplastic neurological syndromes (PNS), which may be unmasked or triggered by ICIs, as well as direct immune-mediated neurotoxicity, potentially occurring in the absence of identifiable neural antibodies. ICI-associated PNS may involve antibodies overlapping with those seen in spontaneous PNS, although clinical presentations can differ, and ongoing research continues to identify novel neural antibodies. Antibodies against adaptor protein 3 subunit B2 (AP3B2) have recently been implicated in neurological disease. However, they have not previously been reported in ICI-associated neurological syndromes. This case expands the spectrum of neural antibodies associated with ICI treatment and supports the concept that ICIs may unmask rare or previously unrecognized autoimmune neurological responses. Although AP3B2 is not traditionally considered a classical PNS marker, its detection in this context highlights the evolving immunological landscape of ICI-associated neurological disease. Therapeutic management remains challenging, with many patients demonstrating limited or transient responses to immunosuppression. We report a 61-year-old man who developed a rapidly progressive cerebellar syndrome leading to immobility after two cycles of pembrolizumab. Cerebrospinal fluid analysis revealed lymphocytic pleocytosis, elevated protein levels, and cerebrospinal fluid–restricted oligoclonal bands. Antibodies against AP3B2 were detected in both serum and cerebrospinal fluid, along with additional antibodies targeting unknown antigens expressed in rat and monkey hippocampal and cerebellar tissue. Brain MRI was unremarkable. High-dose corticosteroid treatment resulted in only transient clinical improvement.

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