Inhibition of long-lived plasma cells, a critical role for Telitacicept treatment to systemic lupus erythematosus

Telitacicept (RC18, RemeGen, Ltd) is a novel human TACI-Fc fusion protein that combines B cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL). RC18 has recently been approved in China for the treatment of systemic lupus erythematosus (SLE), demonstrating its safety and efficacy in the majority of the target population. However, the unique pharmacological mechanism of RC18 has not yet been fully elucidated. In this study, we tested MRL-/lpr mice (a classic SLE animal model) and in vitro LLPCs induced models after RC18 treatment to evaluate the factors contributing to treatment benefits. We found that RC18 delayed the progression of SLE mice by specifically targeting APRIL and long-lived plasma cells (LLPCs). In the SLE animal model, RC18 blocked proteinuria and splenic involvement. RC18 specifically downregulated LLPCs in the bone marrow (BM) compared to other immune cell types. Moreover, the deposition of immune complexes in the kidneys of the RC18 group was also reversed. In vitro, we constructed an LLPCs induction model and verified the direct regulatory ability of RC18 on LLPCs. This study reveals the crucial role of LLPCs in the SLE treatment with RC18, providing a new explanation for the excellent efficacy in clinical practice.