Case report: Granzyme-B expression by T- and B- cells during severe AQP4-positive Neuromyelitis Optica spectrum disorder with fatal venous thromboembolism outcome

Author(s)

Boldrini, Vinicius Oliveira ; Brito, Mariana Rabelo ; Quintiliano, Raphael Patricio Silva ; Scardua Silva, Lucas ; Yasuda, Clarissa Lin ; Cendes, Fernando ; Farias, Alessandro Santos ; Damasceno, Alfredo

• Document type: Journal article
• Source: FRONTIERS IN NEUROLOGY; v. 14, p. 6-pg., 2023-08-17.

Abstract

Background The expression of serine protease granzyme-B (GzmB) by circulating CD8(+) T lymphocytes has been recently suggested as a biomarker for poor immunotherapy response and severe disability in patients with Neuromyelitis Optica spectrum disorders (NMOSD). In parallel, venous thromboembolism (VTE) has been reported mainly in NMOSD patients exhibiting transverse myelitis.Case presentation Here, we describe an Aquaporin-4 positive (AQP4-positive) NMOSD patient who showed short myelitis (SM) and experienced a fatal pulmonary thromboembolism/lower extremity deep vein thrombosis during anti-CD20 treatment. Flow cytometry analyses from the peripheral blood revealed an enhanced cytotoxic behavior through circulating CD8(+)GzmB(+) T, CD4(+)GzmB(+) T lymphocytes, and residual CD19(+)GzmB(+) B cells.Conclusions Fatal VTE may be a rare outcome, particularly in patients exhibiting SM, and may share poorly understood immunological mechanisms with AQP4-positive NMOSD severity. (AU)

• FAPESP's process: 17/21363-5 - Regulation of JAK/STAT/SOCS in the ontogen of IFNg-producing cells derivated from encephalitogenic Th17 cells during the clinical evolution of experimental autoimmune encephalomyelitis
• Grantee: Alessandro dos Santos Farias
• Support Opportunities: Regular Research Grants
• FAPESP's process: 13/07559-3 - BRAINN - The Brazilian Institute of Neuroscience and Neurotechnology
• Grantee: Fernando Cendes
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC