Abstract General Information

Title

Senescent-like phenotype of CD8+ T lymphocytes during AQP4-positive NMOSD treated with Rituximab: Reassessing the similarity between NMOSD and MS?

Case Report

Case presentation: Here we describe a patient diagnosed with Aquaporin-positive (AQP4-positive) Neuromyelitis Optica spectrum disorder (NMOSD) who exhibits longitudinally extensive myelitis in a highly aggressive disease course (EDSS 8.0) even during rituximab treatment. Since the patient agreed to participate in our research, we collected peripheral blood and performed high-dimensional flow cytometry analyses aiming to investigate immunological T cell markers during rituximab treatment. We identified subsets of CD8+ T lymphocytes (CD28-CD57+) associated with serine-protease granzyme-B (GzmB) expression in the peripheral blood during this treatment.
Discussion: In comparison with previous data, CD8+GzmB+ T lymphocytes seem to occur in the peripheral blood of AQP4-positive NMOSD patients in a higher percentage than in healthy donors and similar rates when compared to Multiple Sclerosis (MS) patients. Also, resembling MS, the majority of GzmB expression seems to be derived from CD8+ T lymphocytes exhibiting markers (CD28-CD57+) of terminal differentiation, namely senescent T cells. Yet, following data from MS patients, CD8+GzmB+ T lymphocytes were recently described as correlated with disease disability and poor immunotherapy response during NMOSD.
Final comments: Further investigation regarding specific T cell markers related to GzmB expression, mainly senescent CD8+ T lymphocytes, may provide novel and more accurate targets for antibody monoclonal approaches as well as for accessing prognosis/treatment response during severe AQP4-positive NMOSD clinical courses.