To describe the antibody discovery and clinical characteristics of patients with phosphodiesterase 10A (PDE10A) paraneoplastic autoimmunity.

Paraneoplastic neurological autoimmunity appears to be increasing with the introduction of immune checkpoint inhibitor therapies for cancer. The detection of neural autoantibodies in patients’ serum or CSF confirms the diagnosis.

We describe 7 patients with autoantibodies specific for PDE10A, a striatum-enriched phosphodiesterase. Patient specimens (sera, 7; CSF, 4) produced identical basal ganglia-predominant synaptic staining of murine brain tissue by indirect immunofluorescence. The autoantigen was identified by immunoprecipitation and mass spectrometry as PDE10A, and confirmed by antigen-specific recombinant western blot and cell-based assays, and immune absorption experiments.

Median patient-age was 70 years (range, 66-76), four were men. Four patients had movement disorders (hyperkinetic movement disorders in 3 [chorea, ballismus, dystonia] and parkinsonism in 1). Four had cognitive dysfunction. All patients but one had cancer (lung [adenocarcinoma;1, squamous-cell carcinoma;1, poorly differentiated mesenchymal carcinoma,1], renal adenocarcinoma, 2; and pancreatic adenocarcinoma,1). Two of the 7 patients developed hyperkinetic movement disorders during treatment with immune checkpoint inhibitors. Their MRIs demonstrated FLAIR/T2 basal ganglia hyperintensities, and their CSF harbored unique oligoclonal bands.  One of those patients had significant improvement after corticosteroids. One patient’s renal adenocarcinoma expressed PDE10A by immunohistochemistry. The intracellular location of PDE10A suggests a T-cell mediated pathology targeting cells expressing MHC1-bound-PDE10A peptides.

PDE10A-IgG expands the spectrum of diagnosable paraneoplastic movement disorders. PDE10A-IgG detection should prompt cancer screening in patients without known malignancy. Movement disorders in patients treated with checkpoint inhibitors should raise suspicion for this autoantibody.