#AANAM – AQP4-IgG Testing Approach Shows High Accuracy for NMOSD Diagnosis

Using a live cell-based assay to test for the presence of aquaporin-4 antibodies (AQP4-IgG) can accurately identify people who have neuromyelitis optica spectrum disorder (NMOSD), new research suggests.

Scientists said the cell-based assay was “a highly specific diagnostic biomarker of NMOSD and did not yield false positive results.”

These findings were presented at the annual meeting of the American Academy of Neurology, in a presentation titled “The Positive Predictive Value of Aquaporin-4 Antibody Live Cell-based Assay in a Tertiary Referral Center.” The 2021 virtual AAN meeting is being held online April 17-22.

NMOSD is caused by the immune system launching an erroneous attack on healthy tissue in the brain and spinal cord. In most cases, this immune attack is driven by AQP4-IgG — antibodies that cause an immune system attack against a type of nervous system cell called astrocytes.

Testing for AQP4-IgG is important for diagnosing NMOSD. However, some testing methods have high false-positive rates, limiting their usefulness. In this presentation, researchers from the Mayo Clinic shared data for 1,704 people who underwent AQP4-IgG testing at their center using a new technique.

“The goal of this study is to assess the false positivity rate and the positive predictive value of AQP4-IgG,” Mayra Montalvo, MD, a neurologist at Mayo, said in the presentation. Of note, “positive predictive value” is a statistical measurement that assesses the probability that people with a positive test actually have the disease.

The technique the researchers used for AQP4-IgG testing was fluorescent activated cell sorting, or FACS. Very simply, this is a method in which fluorescent molecules are used to label cells of interest — specifically, immune cells producing AQP4-IgG. The cells then are analyzed one by one using a specialized machine.

Among those tested for AQP4-IgG from January 2018 until the end of 2019, 37 (2%) had a positive result. The median age of patients testing positive was 56 and 81% were female. These patients’ clinical records were reviewed by two neurologists to determine whether they qualified for a diagnosis of NMOSD.

All 37 of the people who tested positive fulfilled the current international diagnostic criteria for NMOSD. Most of these patients had classic signs of the disease, such as optic neuritis —inflammation of the nerves that connect the eyes to the brain — and/or myelitis, or inflammation in the spinal cord.

“There were zero false-positive results, despite a large testing volume [number of patients tested],” Montalvo said.

Since all the patients who tested positive for AQP4-IgG did actually have the disease, the positive predictive value of AQP4-IgG testing was 100%.

“We can conclude that, for AQP4-IgG, the [FACS] assay is highly specific, and it’s a great diagnostic biomarker of NMOSD,” Montalvo said.