Clinical Information

Autoantibodies specific for neurons and muscle are important serological markers of neurological autoimmunity. Most are highly predictive of specific neoplasms that are metastatic when diagnosed, but usually limited in spread to regional lymph nodes and adjacent structures.(1-4)

Collapsin response-mediator protein-5 (CRMP-5) is highly expressed in small-cell lung carcinomas (SCLC), in neurons throughout the adult central and peripheral nervous systems, and in a subset of glial cells.(1) In Western blot analyses the native antigen is a 62-kDa protein (recombinant human CRMP-5 is 68-kDa).(1) CRMP-5-IgG (also known as anti-CV-2)(4,5) is a more common autoantibody accompaniment of SCLC than antineuronal nuclear antibodies-1 (ANNA-1; anti-Hu) and sometimes occurs with thymoma.

The neurological presentation of CRMP-5 seropositive patients is usually multifocal, and can affect any level of the neuraxis. Neurological presentations that suggest a CRMP-5-IgG-related syndrome include subacute chorea or cranial neuropathy (particularly loss of vision, taste, or smell), dementia, myelopathy and gastrointestinal dysmotility in a patient with risk factors for lung cancer, or encephalopathy or neuromuscular hyperexcitability in a patient with serological or clinical evidence of myasthenia gravis.(1) Fourteen percent of patients have thromboembolic phenomena. Seropositive patients who have thymoma usually present with other myasthenia gravis neurological manifestations (eg, encephalopathy, disorders of continuous muscle fiber activity).(3)

CRMP-5-IgG is defined in serum or spinal fluid by its characteristic immunofluorescence (IF) staining pattern on a mixed tissue substrate of adult mouse central and peripheral neurons. However, CRMP-5-IgG is not detectable by standard IF screening if the titer is low (serum <1:240; CSF <1:2) or if coexisting autoantibodies, either neuron-specific or nonorgan-specific antinuclear and antimitochondrial antibodies, preclude identification of CRMP-5-IgG with certainty. In these situations, CRMP-5-IgG may be detected by Western blot analysis.