A recent retrospective study found that serum biomarkers, including glial fibrillary acidic protein, tau, and ubiquitin C-terminal hydrolase L1, distinguish between double seronegative and aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder, which is indicative of the heterogeneous nature of the former condition.
Neuromyelitis optica spectrum disorder (NMOSD) is characterized by recurrent optic neuritis with or without transverse myelitis, mostly associated with the presence of aquaporin-4 (AQP4) antibodies. Some patients with NMOSD have antibodies against myelin oligodendrocyte glycoprotein (MOG). However, a small subgroup of patients labeled as having double seronegative NMOSD (DS-NMOSD) does not have either of the antibodies.
In this study, the authors aimed to identify the biomarker profiles of the two conditions to determine the pathophysiology of DS-NMOSD in adult patients. The study findings are published in the journal Neurology: Neuroimmunology & Neuroinflammation.
Baseline Characteristics
The study included 51 adult patients, of whom 25 were diagnosed with AQP4-NMOSD and 26 were diagnosed with DS-NMOSD. At sampling, the median age of the study cohort was 40.9 (29.2–50.9) years, and the median disease duration was 27.1 (3.1–99) months. Of the total participants, 72.5% were female. Both cohorts were comparable in terms of age, disease duration, gender, and clinical phenotype at onset.
Serum Biomarker Profile
Compared to patients with DS-NMOSD, AQP4-NMOSD patients had significantly higher levels of glial fibrillary acidic protein (GFAP), tau, and ubiquitin C-terminal hydrolase L1 (UCH-L1). On the contrary, both cohorts had similar levels of neurofilament light chain (NfL). The biomarker profile was not significantly different among untreated patients and those receiving chronic treatment.
Biomarkers for Discriminating AQP4-NMOSD and DS-NMOSD
Among the biomarkers, GFAP and tau had the highest sensitivity (0.840 and 0.800, respectively), specificity (0.654 and 0.654, respectively), and accuracy (0.745 and 0.725, respectively) for discriminating AQP4-NMOSD and DS-NMOSD. The area under the curve (AUC) was comparatively higher for the biomarker combination profile compared to a single biomarker.
Biomarkers and Disease Course
During the acute phase of the disease, the levels of NfL were correlated with disease severity in the AQP4-NMOSD cohort and the whole cohort.
Source:
Carta, S., Dinoto, A., Capobianco, M., Valentino, P., Montarolo, F., Sala, A., Reindl, M., Lo Re, M., Chiodega, V., Branger, P., Audoin, B., Aboab, J., Papeix, C., Collongues, N., Kerschen, P., Zéphir, H., Créange, A., Bourre, B., Schanda, K., . . . Mariotto, S. (2024). Serum biomarker profiles discriminate AQP4 seropositive and double seronegative neuromyelitis optica spectrum disorder. Neurology: Neuroimmunology & Neuroinflammation, 11(1). https://doi.org/10.1212/nxi.0000000000200188
