Research Highlights: Treatment for White Blood Cell Malignancies Causes Nervous System Toxicity

By BruceBlaus. When using this image in external sources it can be cited staff (2014). “Medical gallery of Blausen Medical 2014”. WikiJournal of Medicine 1 (2). DOI:10.15347/wjm/2014.010. ISSN 2002-4436. – Own work, CC BY 3.0,

Original Article:

  • The human CD19 antigen is a transmembrane glycoprotein belonging to the immunoglobulin superfamily.
  • CD19 is critically involved in establishing intrinsic B cell signaling thresholds through modulating both B cell receptor-dependent and independent signaling.
  • CD19-directed immunotherapies are clinically effective for treating B cell malignancies but also cause a high incidence of neurotoxicity.
  • A group of patients treated with chimeric antigen receptor T cells or bispecific T cell engager antibodies display severe neurotoxicity.
  • The neurotoxicity includes fatal brain edema associated with T cell infiltration into the brain.
  • The study reports that mural cells, surrounding the endothelium, express CD19.
  • Endothelial cells are critical for blood-brain-barrier integrity.
  • Researchers identify CD19 expression in brain mural cells using single-cell RNA sequencing data and confirm blood vessel staining at the protein level. 
  • CD19 expression in the brain begins early in development alongside the emergence of mural cell lineages and persists throughout adulthood across brain regions.
  • Mouse mural cells demonstrate lower levels of Cd19 expression, suggesting limitations in preclinical animal models of neurotoxicity.
  • Data suggest an on-target mechanism for neurotoxicity in CD19-directed therapies and highlight the utility of human single-cell atlases for designing immunotherapies.


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