Diagnostic and Therapeutic Approach to Autoimmune Neurologic Disorders

A. Sebastian López-Chiriboga, MD; Eoin P. Flanagan, MD


Semin Neurol. 2018;38(3):392-402. 

In This Article

Laboratory Testing for Neuronal Autoantibodies

Autoantibody testing is fundamental for the diagnosis of autoimmune neurologic disorders. In the correct clinical context, it can provide confirmation of an immune-mediated basis for the neurologic symptoms, and in some circumstances guide the search for a specific underlying neoplasm. However, a positive antibody test result should not replace clinical judgement, and clinicians need to be aware of limitations in testing to avoid potential harm with unnecessary immunotherapy. This is particularly important with neural antibodies that do not have a strong association with autoimmune neurologic disorders (e.g., voltage-gated potassium channel complex autoantibodies with negative subtyping for leucine-rich glioma-inactivated 1 [LGI-1] or contactin-associated protein 2 [CASPR2]), or nonneural antibodies such as thyroperoxidase (TPO) antibodies that are positive in 10 to 12% of the healthy population.[9]

Indirect tissue immunofluorescence and immunohistochemistry serve as screening tools for antibody detection, typically confirmed with Western blot for antibodies that bind cytosolic or nuclear antigens. Cell-based assays are utilized for detection of autoantibodies that recognize cell surface proteins; alternatively, detection can be made by the application of patient sera to live neurons. Ion channel antibodies are typically assessed using a radioimmunoprecipitation assay and radioactive iodine–labeled antigen.[10]

If an autoimmune/paraneoplastic disorder is strongly suspected, testing for autoantibodies should be performed in serum and CSF to improve the yield.[11] The sensitivities vary between antibodies; with some, serum testing is preferred (e.g., AQP4 IgG)[12] and with others, CSF is preferred (e.g., NMDA-R).[13]

It is important to be aware that immunotherapy can impact neural autoantibody testing, and therefore testing prior to initiation of immunosuppression is strongly recommended. Testing after a patient has undergone plasma exchange or received other immunosuppressant medications can result in a false-negative result. On the contrary, false positives can occur in patients who have received pooled antibody preparations in the form of intravenous immunoglobulin (IVIG).

Seronegative patients with a suspected autoimmune neurologic diagnosis may harbor unclassified antibodies, and sending sera to research centers that assess for such antibodies is recommended. Not all autoimmune neurologic disorders are accompanied by an antibody and therefore after excluding competing infectious, neoplastic, or other etiologies,[6] a trial of immunotherapy could be considered in carefully selected patients.[14]

Recently, studies have shown the utility of predictive models for neural antibody positivity and immunotherapy response in epilepsy that can help select patients for antibody testing and immunotherapy.[15]