NMOSD shares some similarities with MOGAD. This article explores the various ways that blood neutrophils behave in these two diseases.
Neuromyelitis optica spectrum disorders (NMOSD) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) are both characterized by the presence of neutrophils in CNS lesions. It has been previously shown that NMOSD neutrophils show functional deficiencies. This study, published in the Journal of Neuroinflammation, explored the hypothesis that neutrophil accumulation in the CNS may be facilitated by impairments that affect mechanisms related to neutrophil death. Using in vitro assays, cell death in blood neutrophils from both aquaporin-4-IgG-seropositive (AQP4+) NMOSD and MOGAD patients, as well as healthy controls was evaluated.
A total of 28 patients with AQP4 NMOSD and 19 patients with MOGAD in a stable disease phase were included in thestudy, along with 45 age- and sex-matched healthy controls. In order to induce cell death, isolated neutrophils were cultured with and without phorbol 12-myristate 13-acetate (PMA). PMA-induced NETosis and apoptosis were then analyzed using 7-AAD and annexin-V by flow cytometry. Additionally caspase-3 was assessed by Western blot, myeloperoxidase-DNA (MPO-DNA) complexes were evaluated by ELISA, and reactive oxygen species were evaluated by dihydrorhodamine 123-based cytometric assay.
The authors found that in response to PMA, neutrophils from patients with AQP4+ NMOSD showed an increased survival and a reduced cell death, while this was not true for patients with MOGAD. AQP4+ NMOSD cases also showed a small increase in annexin V+ 7-AAD− early apoptotic neutrophils compared to healthy controls. No differences were found in neutrophil-derived MPO DNA or serum levels of MPO, elastase, IL-6, IL-8, or TNF-ɑ. The authors conclude that although the data show that the apoptotic response is altered while the NETotic response is not altered in these neutrophils, additional research is needed to confirm this.
Schroeder-Castagno, M., Del Rio-Serrato, A., Wilhelm, A., Romero-Suárez, S., Schindler, P., Alvarez-González, C., Duchow, A. S., Bellmann-Strobl, J., Ruprecht, K., Hastermann, M., Grütz, G., Wildemann, B., Jarius, S., Schmitz-Hübsch, T., Paul, F., & Infante-Duarte, C. (2022). Impaired response of blood neutrophils to cell-death stimulus differentiates AQP4-IgG-seropositive NMOSD from MOGAD. Journal of Neuroinflammation, 19(1), 239. https://doi.org/10.1186/s12974-022-02600-0