No Astrocyte Damage Found in Patients Lacking Anti-AQP4 Antibodies

Patricia Inacio, PhD avatar

by Patricia Inacio, PhD |

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People with neuromyelitis optica spectrum disorder (NMOSD), but lacking anti-AQP4 and anti-MOG antibodies, show no signs of damage to astrocytes — nervous system cells attacked in NMOSD — when compared to those with anti-AQP4 antibodies.

Those findings from a recent study suggest that the mechanisms underlying NMOSD symptoms in these patients are likely different than in those with the common anti-AQP4 antibodies. That warrants further research to identify treatment targets, the scientists said.

The study, “CSF GFAP levels in double seronegative neuromyelitis optica spectrum disorder: no evidence of astrocyte damage,” was published in the Journal of Neuroinflammation.

While up to 90% of NMOSD patients test positive for anti-AQP4 (aquaporin-4) antibodies, a subset of cases presenting with NMOSD complications have anti-MOG (myelin oligodendrocyte glycoprotein) antibodies. MOG antibody-associated disease (MOGAD) has been defined as a distinct disease entity.

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However, some patients with NMOSD-like symptoms are negative for both antibodies, which complicates not only their diagnosis, but their treatment. These patients are called “double seronegative.”

Previous reports suggest that the glial fibrillary acidic protein (GFAP) may indicate damage to astrocytes when detected in the cerebrospinal fluid (CSF, the liquid surrounding the brain and spinal cord) of NMOSD patients positive for anti-AQP4 antibodies.

Now, an international team of researchers compared the clinical features, as well as the levels of GFAP in the CSF of patients with double-negative NMOSD (DN-NMOSD) and AQP4-NMOSD.

They analyzed CSF samples collected from 17 patients (mean age 32.3 years) diagnosed with DN-NMOSD from South Korea, Germany, Thailand, and Denmark.

CSF samples from 30 age-matched patients with AQP4–NMOSD (mean age 35.2 years) and 17 with MOGAD (mean age 31.2 years) were included as controls. In addition, a total of 15 patients (mean age 36.8) with other neurological disorders (OND) and without expected damage to astrocytes also were included as controls.

All CSF samples were collected within one month of clinical worsening and, in most cases, before patients started treatment with high-dose steroids.

The levels of GFAP in the CSF were measured twice by a researcher in a blinded manner, meaning no knowledge of diagnosis. Also, the lack of anti-AQP4 antibodies was confirmed using two different methods.

Results showed that DN-NMOSD patients had significantly lower levels of GFAP compared to AQP4–NMOSD patients — median 0.49 vs. 102.9 nanograms per milliliter (ng/mL).

No differences were seen when DN-NMOSD was compared to the other two groups, the OND (median of 0.25 ng/mL) and the MOGAD (median 0.39 ng/mL) groups.

“These results suggest that DN-NMOSD has a different underlying pathogenesis [process] other than astrocytopathy [astrocyte damage], distinct from AQP4–NMOSD,” the scientists wrote.

The team also found that levels of GFAP in the CSF of 90% of patients in the AQP4–NMOSD group were significantly higher than the highest level measured in the OND group.

More studies are required to identify potential treatment targets for DN-NMOSD patients, they added.