ANNA1

ANNA-1, short for anti-neuronal nuclear antibody type 1, is an autoantibody associated with paraneoplastic neurological syndromes. It is commonly referred to as anti-Hu, reflecting its history and target. ANNA-1 antibodies are detected in serum or cerebrospinal fluid of some patients with cancer, most frequently small cell lung carcinoma (SCLC).

Target and mechanism: The antibodies target neuronal Hu proteins (ELAVL family), which are RNA-binding proteins that regulate stability and translation of neuronal mRNA. In paraneoplastic settings, immune responses directed at Hu antigens expressed by tumor cells can cross-react with neurons, causing immune-mediated neuronal injury. The exact mechanisms involve both humoral and cellular components and can vary among patients.

Clinical features: ANNA-1–associated syndromes are a subset of paraneoplastic neurological syndromes and may present as encephalitis, limbic encephalitis, brainstem or cerebellar degeneration, or sensory neuronopathy. Symptoms are typically subacute to progressive and may precede, accompany, or follow cancer diagnosis. A substantial proportion of patients have an occult tumor at presentation; SCLC is the most common association.

Diagnosis and management: Diagnosis relies on detection of ANNA-1 antibodies in serum or CSF using immunoblot, immunoprecipitation, or indirect immunofluorescence assays, often as part of a broader paraneoplastic antibody panel. Because ANNA-1 positivity signals an underlying malignancy, comprehensive cancer screening is recommended. Management focuses on treating the tumor and on immunotherapy (e.g., corticosteroids, IV immunoglobulin, plasmapheresis) to address neurological symptoms; outcomes vary and can be limited by advanced disease.

Prognosis and research: The presence of ANNA-1 antibodies reflects an autoimmune paraneoplastic process and is not specific to a single cancer type. Ongoing research seeks to clarify pathogenic roles, refine diagnostic panels, and improve treatment strategies.