Reconstitution of peripheral blood T cell receptor β immune repertoire in immune checkpoint inhibitors associated myocarditis

被引:0
|
作者
Yan, Peng [1 ]
Liu, Yanan [1 ]
Zhang, Mingyan [2 ]
Liu, Ning [1 ]
Zheng, Yawen [1 ]
Zhang, Haiqin [1 ]
Zhou, Hao [3 ]
Sun, Meili [1 ]
机构
[1] Shandong First Med Univ, Jinan Cent Hosp, Dept Oncol, Jinan, Peoples R China
[2] Shandong Univ, Cheeloo Coll Med, Jinan, Peoples R China
[3] Shandong First Med Univ, Grad Sch, Jinan, Peoples R China
关键词
TCR; CDR3; Immune Repertoire; ICIs-associated myocarditis; High-throughput sequencing; DIVERSITY; TOXICITIES;
D O I
10.1186/s40959-024-00230-4
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Purpose Immune checkpoint inhibitors (ICIs)-associated myocarditis was a rare yet severe complication observed in individuals undergoing immunotherapy. This study investigated the immune status and characteristics of patients diagnosed with ICIs- associated myocarditis.Methods A total of seven patients diagnosed with ICIs-associated myocarditis were included in the study, while five tumor patients without myocarditis were recruited as reference controls. Additionally, 30 healthy individuals were recruited as blank controls. Biochemical indices, electrocardiogram, and echocardiography measurements were obtained both prior to and following the occurrence of myocarditis. High-throughput sequencing of T cell receptor (TCR) was employed to assess the diversity and distribution characteristics of TCR CDR3 length, as well as the diversity of variable (V) and joining (J) genes of T lymphocytes in peripheral blood.Results In the seven patients with ICIs-associated myocarditis, Troponin T (TNT) levels exhibited a significant increase following myocarditis, while other parameters such as brain natriuretic peptide (BNP), QTc interval, and left ventricular ejection fraction (LVEF) did not show any significant differences. Through sequencing, it was observed that the diversity and uniformity of CDR3 in the ICIs-associated myocarditis patients were significantly diminished. Additionally, the distribution of CDR3 nucleotides deviated from normality, and variations in the utilization of V and J gene segments.Conclusion The reconstitution of the TCR immune repertoire may play a pivotal role in the recognition of antigens in patients with ICIs-associated myocarditis.
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页数:11
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