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HelpTest Code CRMWS Collapsin Response-Mediator Protein-5-IgG, Western Blot, Serum
Reporting Name
CRMP-5-IgG Western Blot, SUseful For
Evaluation of cases of chorea, vision loss, cranial neuropathy and myelopathy
Method Name
Western Blot
Performing Laboratory
Mayo Clinic Laboratories in Rochester
Specimen Type
SerumOrdering Guidance
It is recommended an evaluation be ordered in conjunction with this testing if not previously performed. Multiple neurological phenotype-specific autoimmune/paraneoplastic evaluations are available. For more information as well as phenotype-specific testing options, see Autoimmune Neurology Test Ordering Guide.
Additional Testing Requirements
Necessary Information
Provide the following information:
-Relevant clinical information
-Ordering healthcare professional name, phone number, mailing address, and e-mail address
Specimen Required
Supplies: Sarstedt Aliquot Tube 5 mL (T914)
Collection Container/Tube:
Preferred: Red top
Acceptable: Serum gel
Submission Container/Tube: Plastic vial
Specimen Volume: 1.5 mL
Collection Instructions: Centrifuge and aliquot serum into a plastic vial.
Specimen Minimum Volume
1 mL
Specimen Stability Information
| Specimen Type | Temperature | Time | Special Container |
|---|---|---|---|
| Serum | Refrigerated (preferred) | 28 days | |
| Frozen | 28 days | ||
| Ambient | 72 hours |
Reject Due To
| Gross hemolysis | Reject |
| Gross lipemia | Reject |
| Gross icterus | Reject |
Reference Values
Negative
Day(s) Performed
Monday through Thursday
CPT Code Information
84182
LOINC Code Information
| Test ID | Test Order Name | Order LOINC Value |
|---|---|---|
| CRMWS | CRMP-5-IgG Western Blot, S | 47401-5 |
| Result ID | Test Result Name | Result LOINC Value |
|---|---|---|
| 83107 | CRMP-5-IgG Western Blot, S | 47401-5 |
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.
Interpretation
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
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
1. Yu Z, Kryzer TJ, Griesmann GE, et al. CRMP-5 neuronal autoantibody: marker of lung cancer and thymoma-related autoimmunity. Ann Neurol. 2001;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;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;48(2-3):85
5. Klein CJ. Autoimmune-mediated peripheral neuropathies and autoimmune pain. In: Pittock SJ, Vincent A, eds. Handbook of Clinical Neurology; Autoimmune Neurology. Elsevier; 2016 pp 417-446
Method Description
Western blot is performed on denatured full-length recombinant human collapsin response-mediator protein-5 (CRMP-5), reduced and subjected to electrophoresis on 10% polyacrylamide gel. IgG is detected autoradiographically by enhanced chemiluminescence.(Yu Z, Kryzer TJ, Griesmann GE, et al. CRMP-5 neuronal autoantibody: marker of lung cancer and thymoma-related autoimmunity. Ann Neurol. 2001;49[2]:146-154; Dubey D, Jitprapaikulsan J, Bi H, et al. Amphiphysin-IgG autoimmune neuropathy: A recognizable clinicopathologic syndrome. Neurology. 2019;93[20]:e1873-e1880. doi:10.1212/WNL.0000000000008472)