Abstract:

Systemic lupus erythematosus (SLE) is a complex autoimmune disease for which traditional treatments often show limited efficacy in severe and refractory cases. Recently, chimeric antigen receptor (CAR) T cell therapy has emerged as a novel immunotherapy strategy, demonstrating significant efficacy in preliminary studies for SLE treatment. Biomarkers are crucial for the precise assessment of treatment efficacy and safety. Biomarkers for monitoring the efficacy of CAR T cell therapy include traditional markers and markers related to CAR T therapy. Traditional markers for SLE disease monitoring, such as decreased titers of serum anti-double-stranded DNA, anti-single-stranded DNA, anti-nucleosome autoantibodies, normalization of serum complement levels, and improvement of urine protein/creatinine ratio, indicate that the disease is effectively controlled and can still be used for baseline follow-up and disease monitoring during CAR T cell therapy. B cell markers indicating effective CAR T therapy include a decrease in the number of B cells after infusion, a B cell phenotype dominated by the naive B cell, and a significant decrease in the proportion of memory B cells and plasmablasts. Regarding T cell markers related to CAR T therapy, the high proportion of naive T cell (CD45RA+CD27+) and central memory T cell (CD45RA-CD62L+CD27+) subsets before infusion indicate stronger anti-tumor efficacy; The initial expression of transcription factors associated with early memory differentiation on patients’ CAR T cells, such as T cell factor 7 (TCF7) and lymphoid enhancer‐binding factor 1 (LEF1), suggest that these patients may be sensitive to CAR T therapy. After infusion, high expression of T cell activation markers (CD25, CD69 and CD137), and exhaustion markers (CD57, PD-1, and Tim-3) indicate that T cells are in a state of dysfunction, with limited expansion, cytokine secretion and cell killing capabilities. Safety markers, including effector cytokines secreted by CAR T cells [interleukin(IL)-2 and IFN-γ] and cytokines produced by monocytes and macrophages (IL-1 and IL-8), can be used to monitor the most common toxicities and side-effects of CAR T-cell therapies, cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS).High levels of serum macrophage inflammatory protein-1α (MIP-1α) are of high value for predicting the risk of severe CRS and ICANS after CAR T-cell therapy. In addition, haematotoxicity markers include baseline platelet count and absolute neutrophil count, and an infection-related prediction model consisting of IL-8, IFN-γ and IL-1β are effective in predicting the risk of severe infection in patients after infusion.The design of the CAR receptor structure, the chemotherapeutic modality used to remove the lymphocytes, as well as the choice of treatments that the patient had received and the autoimmune status, all affect the efficacy and safety. A comprehensive and standardised testing and evaluation system should be included in current and future clinical studies to provide a comparative standard for the use of CAR T-cell therapy in autoimmune diseases such as SLE.

Key words:Systemic lupus erythematosus,Chimeric antigen receptor T cell therapy,Biomarkers