anti-Tr antibodies

Anti-Tr/DNER antibodies are onconeural antibodies directed against the DNER protein expressed on Purkinje cells in the cerebellum. They are a classic serologic marker for paraneoplastic cerebellar degeneration (PCD), and among paraneoplastic antibodies, anti-Tr has one of the strongest associations with Hodgkin lymphoma (though it can rarely be seen with other lymphomas). Pathophysiology involves an autoimmune attack—thought to be primarily antibody-mediated but with likely contribution from cytotoxic T cells—against Purkinje cells, causing their degeneration and loss, which leads to irreversible cerebellar dysfunction even if the underlying tumor is treated. Clinically, patients present with a subacute, progressive cerebellar syndrome: gait ataxia, limb ataxia, dysarthria, nystagmus, and diplopia, often evolving over weeks. Unlike some other paraneoplastic syndromes, neurologic symptoms often precede the diagnosis of the underlying malignancy, prompting a thorough oncologic workup (including PET/CT and consideration of lymph node biopsy) upon identification of these antibodies. MRI findings may be normal early on, later showing cerebellar atrophy. CSF often shows lymphocytic pleocytosis and elevated protein with oligoclonal bands. Treatment focuses on identifying and treating the underlying malignancy (e.g., chemotherapy/radiation for Hodgkin lymphoma) as well as immunotherapy (IVIG, corticosteroids, plasmapheresis, or rituximab), though neurologic recovery is often limited due to irreversible Purkinje cell loss. This antibody is part of the broader category of onconeural antibodies (along with anti-Yo, anti-Hu, anti-Ri, anti-CV2/CRMP5, anti-Ma2) tested for in paraneoplastic neurologic syndrome panels, each with characteristic tumor and clinical associations that are high-yield for boards (e.g., anti-Yo with ovarian/breast cancer causing PCD, anti-Hu with small cell lung cancer causing sensory neuronopathy/encephalomyelitis).