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Published on: November 17, 2020
CNS immune remodelling in SLE associated with anti-CD19 CAR-T therapy
Jinjian Sun1, Xiaoru Hu2, Weina Li3
1Department of Rheumatology, Xiangya Hospital, Central South University, Changsha, Hunan, China; Provincial Clinical Research Center for Rheumatic and Immunologic Diseases, Xiangya Hospital, Central South University, Changsha, Hunan, China; National Clinical Research Center for Geriatric Disease, Xiangya Hospital, Central South University, Changsha, Hunan, China; Department of General &Vascular Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Chimeric antigen receptor T-cell (CAR-T) therapy for systemic lupus erythematosus (SLE) remodels the central nervous system (CNS) immune environment. CAR-T cells were detected in the CNS, influencing T-cell dynamics and immune cell interactions.
Area of Science:
- Immunology
- Neuroscience
- Genomics
Background:
- Refractory systemic lupus erythematosus (SLE) poses challenges for treatment.
- Autologous anti-CD19 chimeric antigen receptor T-cell (CAR-T) therapy is a promising treatment for SLE.
- The impact of CAR-T therapy on central nervous system (CNS) immune remodeling and neurotoxicity in SLE is not well understood.
Purpose of the Study:
- To investigate the effects of CAR-T therapy on CNS immune composition in patients with SLE.
- To identify cellular and molecular features associated with CAR-T therapy in the CNS.
- To explore potential mechanisms of CAR-T-associated neurotoxicity in SLE.
Main Methods:
- Integrated single-cell RNA/T-cell receptor (TCR) sequencing and Olink proteomics were performed on cerebrospinal fluid (CSF) from SLE patients before and after CAR-T therapy.
- Longitudinal sampling captured dynamic changes at different time points post-treatment.
- Analysis included profiling of immune cell populations, T-cell states, ligand-receptor interactions, and TCR repertoire.
Main Results:
- Single-cell profiling revealed dynamic changes in CNS immune cell composition following CAR-T therapy, particularly in T cells.
- CAR-T cells were detected in the CNS, exhibiting proliferative and cytotoxic states early post-treatment, shifting to memory and exhaustion phenotypes later.
- Endogenous T cells showed diverse effector subsets, with CD4+ T cells enriched for type I interferon signaling, and extensive myeloid-lymphocyte interactions were observed.
Conclusions:
- CAR-T therapy is associated with significant CNS immune remodeling in SLE patients.
- The study provides cellular and molecular insights into CNS immune responses during CAR-T treatment.
- Findings may guide future research on CNS immunity and neurotoxicity in the context of CAR-T therapy for autoimmune diseases.
