诊断学理论与实践 ›› 2024, Vol. 23 ›› Issue (03): 263-269.doi: 10.16150/j.1671-2870.2024.03.003
收稿日期:
2024-04-23
接受日期:
2024-05-23
出版日期:
2024-06-25
发布日期:
2024-06-25
通讯作者:
吕良敬 E-mail:lu_liangjing@163.com基金资助:
Received:
2024-04-23
Accepted:
2024-05-23
Published:
2024-06-25
Online:
2024-06-25
摘要:
系统性红斑狼疮(systemic lupus erythematosus, SLE)是一种复杂的自身免疫疾病,传统治疗在部分重度和难治性患者中效果有限。近期研究显示,嵌合抗原受体(chimeric antigen receptor, CAR)T细胞疗法在SLE治疗中展现出了具有前景的疗效。生物标志物在精准评估治疗效果和安全性方面至关重要,CAR T细胞治疗与安全性评估标志物包括传统标志物和与CAR T细胞疗法相关的标志物。传统的SLE病情监测标志物,仍可用于CAR T细胞治疗基线随访和病情监测,如血清抗双链DNA、抗单链DNA和抗核小体等自身抗体的滴度下降,血清补体水平恢复正常,以及尿蛋白/肌酐比值的改善,均提示病情得到有效控制。CAR T细胞疗效监测标志物分为B细胞和T细胞标志物。输注后,B细胞数量下降,B细胞表型以初始B细胞为主,记忆B细胞和浆母细胞的比例显著降低,表明治疗取得了疗效。输注前,初始T细胞(CD45RA+CD27+)和中央记忆型T细胞(CD45RA-CD62L+CD27+)的高比例则提示更强的抗肿瘤效应;患者的CAR T细胞表达与早期记忆分化相关的转录因子,如T细胞因子7和淋巴增强子结合因子1,提示这些患者对CAR T细胞疗法更为敏感。输注后,CD25、CD69和CD137等T细胞激活标志物,以及CD57、PD-1和Tim-3等耗竭标志物的高表达,提示T细胞的杀伤能力受到限制。CAR T细胞治疗安全性标志物不仅包括CAR T细胞分泌的效应细胞因子(如白细胞介素-2和IFN-γ),还包括单核细胞和巨噬细胞产生的细胞因子(如IL-1和IL-8),其水平可用于评估CAR T细胞疗法最常见的毒副反应[细胞因子释放综合征(cytokine release syndrome, CRS)和免疫效应细胞相关神经毒性综合征(immune effector cell-associated neurotoxicity syndrome, ICANS)]。高水平的血清巨噬细胞炎性蛋白1α对于预测CAR T细胞治疗后发生严重CRS和ICANS的风险具有较高的价值。此外,基线血小板计数和中性粒细胞绝对值可预测血液毒性,由IL-8、IFN-γ和IL-1β组成的感染相关预测模型,能够有效预测患者输注后出现严重感染的风险。CAR受体结构设计、清除淋巴细胞的化疗方式,患者曾接受的治疗选择及自身免疫状态等都会影响CAR T细胞治疗的疗效及安全性。在当前及未来将开启的相关临床研究中,应纳入全面、规范的检测和评估体系,为CAR T细胞疗法在SLE等自身免疫疾病的应用,提供比较标准。
中图分类号:
王一阳, 吕良敬. 系统性红斑狼疮CAR T细胞治疗疗效预测及安全性评估的潜在生物标志物[J]. 诊断学理论与实践, 2024, 23(03): 263-269.
WANG Yiyang, LÜ Liangjing. Potential biomarkers for prediction of the efficacy and safety of CAR T cell treatment in systemic lupus erythematosus[J]. Journal of Diagnostics Concepts & Practice, 2024, 23(03): 263-269.
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