What are paraneoplastic antibody panels?

A:Paraneoplastic antibody panels are laboratory tests used to aid in the diagnosis of paraneoplastic neurologic syndromes (PNS), which are autoimmune disorders that afflict the central or peripheral nervous system. Because of the rarity of PNS and resemblance to more common pathologies such as schizophrenia, stroke, or infection, diagnosing PNS can be challenging. Fortunately, many patients with PNS frequently have circulating antibodies against neuronal self-antigens that paraneoplastic antibody panels can detect.

Paraneoplastic antibody panels often consist of multiple antibodies known to cause or be associated with PNS. Due to the complexity of the testing and the low prevalence of these disorders, these panels are often only available at reference labs.

When should these antibody panels be used?

Ideally, antibody panels should only be ordered by a neurologist and only if there is a strong clinical suspicion of PNS. This often means excluding other disorders, such as a stroke or viral encephalitis, before proceeding with antibody testing. While it is tempting to use the panels as a screen, indiscriminate usage in low-risk patients can result in false positives, delaying an accurate diagnosis.

What are the pros and cons of paraneoplastic antibody testing?

Paraneoplastic antibody testing can be a useful diagnostic tool for patients with a strong clinical suspicion of PNS. For example, in a woman with rapid onset ataxia and ovarian cancer, a high titer of the PCA-1 antibody strongly indicates paraneoplastic cerebellar degeneration. It may also indicate a poor prognosis, and that the neuronal damage is likely permanent. It is important to note, though, that a diagnosis of PNS can be made without antibody testing.

As mentioned above, the problems with these panels arise when they are used indiscriminately or as a screening tool. In a study by Ebright MJ, et al. (Neurology 2018;91:e2057-66), patients with a moderate or low clinical suspicion of PNS yielded no true positive panels. In addition, only panels ordered by neurology contained true positives. However, even when ordered by neurology, multiple institutions have found that the positive predictive value of the panels is low, often <20%.

The high false positive rate can be attributed to multiple features of the test, including the methodology for antibody detection, the specimen type selected, and what antibodies are being evaluated. Many antibodies associated with PNS can be found in the general population and may not be pathogenic or are indicative of non-PNS diseases. For example, the GAD-65 antibody, which is associated with Stiff Person Syndrome and multiple other paraneoplastic disorders, is present in 1% of the general population and roughly 80% of type-1 diabetics.

What methods can be used to screen patients who are unlikely to benefit from these antibody panels?

The Antibody Prevalence in Epilepsy and Encephalopathy (APE2) Score, developed at the Mayo Clinic, can be a very useful screening tool. In a retrospective study, Dartmouth Hitchcock Medical Center found that the APE2 score was able to identify approximately 90% of patients who would have had a true positive paraneoplastic antibody panel result, and approximately 80% of patients who would have had a false positive or negative panel (J Appl Lab Med 2021;7:36-45). However, the APE2 score can only be applied to certain PNS disorders, meaning that it cannot be used as a universal screen for antibody testing.

How can laboratorians work with clinicians to use these panels more effectively?

The most important thing the lab can do is to maintain an open dialogue with clinicians. Working with neurology, the lab needs to educate ordering providers on how the panels are intended to be used, and the problems associated with using them as a screen for low-risk patients. In addition, the lab can utilize various ordering practices, such as restricting PNS panel testing to neurology, or encouraging use of the APE2 score.

Brad Poore, PhD, is the scientific director for clinical chemistry at Sentara Healthcare in Norfolk, Virginia. +Email: [email protected]