Clinical Information

Antineuronal nuclear autoantibody type 2 (ANNA-2), also known as anti-Ri, is an IgG serologic marker of paraneoplastic neurologic autoimmunity and reflects an immune response to neuronal antigens expressed in certain breast, lung, or gynecologic cancers. These carcinomas are often occult, with patients presenting with unexplained signs of neurologic dysfunction. ANNA-2 is far less common than ANNA-1. It is one of the rarest paraneoplastic antibodies encountered in the Mayo Clinic Neuroimmunology Laboratory.

Patients who are seropositive for ANNA-2 usually present to a neurologist with signs of midbrain, brain stem, cerebellar, or spinal cord dysfunction. Some have sensorimotor neuropathy. Ocular opsoclonus-myoclonus, laryngospasm, or jaw-opening dystonia may be prominent. Peripheral neuropathic sign and symptoms may occur. These often reflect coexisting autoimmunity to other onconeural proteins (eg, ANNA-1, collapsin response-mediator protein-5 [CRMP-5], calcium channels); coexisting paraneoplastic autoantibodies are found in 73% of cases.

ANNA-2-positive patients are female in 64% of cases. Most have a primary carcinoma of breast or lung; gynecologic cancer is less frequent.

Treatment of the cancer can lead to progressive reduction in ANNA-2 titer and stabilization or striking improvement of the neurologic disorder.

ANNA-2 is not detected in serum or spinal fluid of healthy individuals. It is found in less than 2% of patients who have small-cell lung carcinoma without evidence of neurologic dysfunction.

ANNA-2 is identified by an indirect immunofluorescence assay. It characteristically stains neurons in the central nervous system and spares neurons in the peripheral nervous system. ANNA-2 is also identifiable by neuronal Western blot characteristics.