Risk of false positives with AQP4 ELISA methodology
Clinical cases: Neurology
Background
A 54-year-old man presents with progressive numbness in his arms and reverse Lhermitte’s phenomenon (numbness provoked by neck extension), which has worsened over the course of seven months. MRI testing shows evidence of a longitudinal extensive T2 hyperintense lesion extending from C3–C6, as well as a transverse band — or pancake-like appearance — of enhancement just below the site of cervical spondylosis at C5–C6 with signal abnormalities and enhancement persisting on MRI over the course of four months. Cerebrospinal fluid analysis reveals a white blood cell count of 1 cell/μL, protein of 54 mg/dL, and normal glucose. His serum aquaporin-4 (AQP4) antibody by ELISA technique from an outside laboratory is positive at 3.3 (normal < 2.9). The patient is diagnosed with neuromyelitis optica spectrum disorder, and lifelong immunosuppressant treatment is considered.
Eventually, a referral is made to Mayo Clinic for further evaluation. The patient undergoes an AQP4-IgG via fluorescence-activated cell sorting (FACS) testing at Mayo Clinic Laboratories, which is negative. The MRI and spinal fluid findings are highly consistent with cervical spondylotic myelopathy with enhancement, and the patient was referred for neurosurgical correction.
Teaching points
- Potential for low positive AQP4 antibodies using the ELISA technique.
- The FACS assay for AQP4 has extremely high specificity (>99%) compared to the high risk of false positives with ELISA testing.
- The MRI findings and their evolution are highly consistent with cervical spondylotic myelopathy with enhancement, with a transverse band of enhancement that is very characteristic and occurs in approximately 7% of cervical spondylotic myelopathies.
- There are potential risks when false positives like this occur. This patient could have been placed on lifelong immunosuppression, which is not what he needed, and would not have had his spine surgically corrected.
Learn more about the risks of false positives with AQP4 ELISA methodology in CNS demyelinating disease testing.
