Immune Checkpoint Inhibitor-associated Kelch-like Protein-11 IgG Rhombencephalitis
Albert Aboseif1, Nisa Vorasoot1, Marcus Vinicius Pinto1, Yong Guo1, Shemonti Hasan1, Anastasia Zekeridou2, John Chen3, Divyanshu Dubey2
1Department of Neurology, 2Department of Laboratory Medicine and Pathology, 3Department of Ophthalmology, Mayo Clinic
Objective:
To report a novel immune checkpoint inhibitor (ICI)-associated seropositive neurological immune-related adverse effect (nirAE).
Background:
ICIs are increasingly linked with several rare neural autoantibodies associated with autoimmune encephalitis. Kelch-like protein-11 (KLHL11)-IgG is an autoantibody usually associated with rhombencephalitis and seminoma. It has not previously been described in the setting of nirAE or in association with esophageal adenocarcinoma.
Design/Methods:
Case report.
Results:
A 61-year-old male was diagnosed with metastatic esophageal adenocarcinoma, and treated with folinic acid, fluorouracil, oxaliplatin (FOLFOX), and nivolumab. Two months after treatment initiation, he developed diplopia and vertigo. Due to a concern for ICI-associated myasthenia gravis, nivolumab was held, and he was started on prednisone and pyridostigmine. EMG showed no neuromuscular junction dysfunction, and acetylcholine-receptor antibodies were negative. MRI brain was unrevealing. Over the next three months, he developed progressive ataxia and gait instability, becoming walker dependent. Examination revealed bi-directional torsional nystagmus, a right upper-extremity wing-beating tremor, and a wide-based ataxic gait. His CSF was non-inflammatory. On further testing, murine brain tissue immunofluorescence assay revealed a neural-specific pattern with periventricular punctate staining consistent with KLHL11-IgG in both serum and CSF, with a titer of 1:7680 and 1:64 respectively, and confirmed by cell-based assay. Tumor histopathology demonstrated poorly differentiated and highly proliferative adenocarcinoma with increased mitotic figures and cytoplasmic KLHL11 immunoreactivity. His diagnosis was consistent with post ICI-associated KLHL11-IgG rhombencephalitis, and he was initiated on 6-months of cyclophosphamide in addition to FOLFOX.
Conclusions:
We report KLHL11-IgG rhombencephalitis associated with poorly differentiated esophageal cancer as a novel nirAE. Tumor staining revealed KLHL11 immunoreactivity, supporting an ICI-associated paraneoplastic syndrome. It is critical to recognize and report novel nirAEs, in an effort to initiate early treatment and prevent progressive neurological disability.