antiCDR2

Anti-CDR2 antibodies, commonly referred to as anti-Yo antibodies, are autoantibodies directed against the cerebellar degeneration-related protein 2 (CDR2). They occur in the setting of paraneoplastic neurologic syndromes, most characteristically paraneoplastic cerebellar degeneration (PCD).

Clinically, patients develop subacute cerebellar signs such as gait ataxia, limb dyscoordination, dysarthria, and nystagmus, typically over weeks to months. In women, anti-Yo–associated PCD is frequently linked to an underlying gynecologic or breast malignancy, most commonly ovarian cancer. The neurological syndrome often precedes the cancer diagnosis, prompting cancer screening when this antibody is detected.

Pathophysiology is believed to involve an anti-tumor immune response in which CDR2 is aberrantly expressed by tumor cells, triggering autoreactive T cells and autoantibody production that damage cerebellar Purkinje cells. The antibodies themselves may serve mainly as disease markers, while T-cell–mediated cytotoxicity is considered central to neuronal injury.

Diagnosis relies on detecting anti-Yo/anti-CDR2 antibodies in serum or cerebrospinal fluid, which supports the diagnosis of a paraneoplastic cerebellar syndrome. Neuroimaging may be normal in early stages and show cerebellar atrophy later. A comprehensive search for an underlying malignancy is indicated, typically guided by patient age and risk factors, with imaging targeted to gynecologic and breast tissues.

Management centers on identifying and treating the underlying tumor; immunotherapies such as steroids, intravenous immunoglobulin, or plasmapheresis may be attempted but are of variable benefit. The prognosis is guarded, with many patients experiencing persistent ataxia despite tumor treatment.