Test Catalog

Test ID: CRMWS    
Collapsin Response-Mediator Protein-5-IgG, Western Blot, Serum

Useful For Suggests clinical disorders or settings where the test may be helpful

Evaluation of cases of chorea, vision loss, cranial neuropathy and myelopathy

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

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 (CSF) 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.

Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.


Interpretation Provides information to assist in interpretation of the test results

A positive result confirms that a patient's subacute neurological disorder has an autoimmune basis, and is likely to be associated with a small-cell lung carcinoma (SCLC) or thymoma, which may be occult.(1,2) A positive result has a predictive value of 90% for neoplasm (77% SCLC, 6% thymoma).(1) Seropositivity is found in approximately 3% of patients who have SCLC with limited metastasis without evidence of neurological autoimmunity.(6)


Clinical-serological correlations have not yet been established for children.


Western blot analysis is indicated when interfering nonorgan-specific or coexisting neuron-specific autoantibodies in serum or spinal fluid preclude unambiguous detection of CRMP-5-IgG by indirect immunofluorescence assay, or when the immunofluorescence assay is negative in a patient whose neurological presentation suggests a CRMP-5-IgG-related syndrome.

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

Seronegativity does not exclude the presence of a neoplasm.

Supportive Data

In the Neuroimmunology Laboratory's current clinical service activity, the frequency of collapsin response-mediator protein-5-IgG (CRMP-5-IgG) detection is approximately 2 per 1,000 sera tested, approximating that of the Purkinje cell cytoplasmic autoantibody-type 1 (PCA-1, or anti-Yo). A lung carcinoma was found in 77% of 116 patients, mostly limited small cell type; 6% had thymoma, and 7% had miscellaneous neoplasms.

Clinical Reference Recommendations for in-depth reading of a clinical nature

1. Yu Z, Kryzer TJ, Griesmann GE, et al: CRMP-5 neuronal autoantibody: marker of lung cancer and thymoma-related autoimmunity. Ann Neurol 2001 February;49(2):146-154

2. Vernino S, Tuite P, Adler CH, et al: Paraneoplastic chorea associated with CRMP-5 neuronal antibody and lung carcinoma. Ann Neurol 2002 May;51(5):625-630

3. Vernino S, Lennon VA: Autoantibody profiles and neurological correlations of thymoma. Clin Cancer Res 2004;10(21):7270-7275

4. Galanis E, Frytak S, Rowland KM Jr, et al: Neuronal autoantibody titers in the course of small cell lung carcinoma and platinum associated neuropathy. Cancer Immunol Immunother 1999 May-June;48(2-3):85

5. Klein CJ: Autoimmune-mediated peripheral neuropathies and autoimmune pain In Handbook of Clinical Neurology; Autoimmune Neurology. Edited by SJ Pittock, A Vincent.  Elsevier; 2016 pp 417-446