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

Vinícius Oliveira Boldrini; Mariana Rabelo Brito; Raphael Patrício Silva Quintiliano; Lucas Scárdua Silva; Clarissa Lin Yasuda; Fernando Cendes; Alessandro Santos Farias; Alfredo Damasceno

doi:10.3389/fneur.2023.1208977

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

Front Neurol. 2023 Aug 17:14:1208977. doi: 10.3389/fneur.2023.1208977. eCollection 2023.

Authors

Affiliations

¹ Neuroimaging Laboratory, Department of Neurology, University of Campinas, Campinas, São Paulo, Brazil.
² Brazilian Institute of Neuroscience and Neurotechnology (BRAINN), University of Campinas, Campinas, São Paulo, Brazil.
³ Neuroimmunology Unit, Department of Genetics, Evolution, Microbiology and Immunology, Institute of Biology, University of Campinas, Campinas, São Paulo, Brazil.
⁴ Autoimmune Research Laboratory, Department of Genetics, Evolution, Microbiology and Immunology, Institute of Biology, University of Campinas, Campinas, São Paulo, Brazil.

^# Contributed equally.

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.

Keywords: B cells; Devic's syndrome; T lymphocytes; anti CD20 monoclonal antibody; deep vein thrombosis (DVT); granzyme-B; neuroinflammation; pulmonary thromboembolism.

Publication types

Case Reports

Grants and funding

This study was supported by the São Paulo Research Foundation (FAPESP) (grant numbers: 2013/07559-3; 2017/21363-5), the National Council for Scientific and Technological Development (CNPQ) (grant number: 315953/2021-7), the Coordination for the Improvement of Higher Education Personnel (CAPES) (Finance Code 001), and the European Charcot Foundation (ECF) (Fellow Community Small Grant Fund).