Abstract General Information
Senescent-like phenotype of CD8+ T lymphocytes during AQP4-positive NMOSD treated with Rituximab: Reassessing the similarity between NMOSD and MS?
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.
Immunology and basic Science
Vinícius Oliveira Boldrini, Raphael Patrício Silva Quintiliano, Natália Munhoz, Mariana Moreira Soares Sa, Clarissa Lin Yasuda, Fernando Cendes, Alfredo Damasceno, Alessandro Santos Farias