Ublituximab: A new FDA-approved anti-CD20 mAb for relapsing forms of multiple sclerosis.

Ublituximab, an intravenous glycoengineered chimeric anti-CD20 IgG1 monoclonal antibody (mAb), is a new FDA-approved treatment for relapsing forms of Multiple Sclerosis (MS). Reassembling the other three anti-CD20 mAbs already in use for MS (rituximab, ocrelizumab and ofatumumab), ublituximab leads to depletion of B cells but spars long-lived plasma cells. Here, we discuss the main findings obtained during the phase 3 clinical trials (ULTIMATE I and II) for ublituximab versus teriflunomide. The current emergence and approval of new anti-CD20 mAbs with different dose regimens, routes of application, glycoengineering and mechanisms of action may contribute to different clinical outcomes.

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

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.