Doerflinger Marcel, Garnham Alexandra L, Freytag Saskia, Harrison Simon J, Prince H Miles, Quach Hang, Slavin Monica A, Pellegrini Marc, Teh Benjamin W
Infectious Disease and Immune Defence Division Walter and Eliza Hall Institute Parkville VIC Australia.
Department of Medical Biology University of Melbourne Melbourne VIC Australia.
Clin Transl Immunology. 2021 Jan 7;10(1):e1235. doi: 10.1002/cti2.1235. eCollection 2021.
Patients with multiple myeloma (MM) are at increased risk for infection. Clinical assessment of infection risk is increasingly challenging in the era of immune-based therapy. A pilot systems-level immune analysis study to identify predictive markers for infection was conducted.
Patients with relapsed and/or refractory MM (RRMM) who participated in a treatment trial of lenalidomide and dexamethasone were evaluated. Data on patient demographics, disease and episodes of infection were extracted from clinical records. Peripheral blood mononuclear cells (PBMCs) collected at defined intervals were analysed, with or without mitogen re-stimulation, using RNA sequencing and mass cytometry (CyTOF). CyTOF-derived cell subsets and RNAseq gene expression profiles were compared between patients that did and did not develop infection to identify immune signatures that predict infection over a 3-month period.
Twenty-three patients participated in the original treatment trial, and we were able to access samples from 17 RRMM patients for further evaluation in our study. Nearly half the patients developed an infection (8/17) within 3 months of sample collection. Infections were mostly clinically diagnosed (62.5%), and the majority involved the respiratory tract (87.5%). We did not detect phenotypic or numerical differences in immune cell populations between patients that did and did not develop infections. Transcriptional profiling of stimulated PBMCs revealed distinct Th2 immune pathway signatures in patients that developed infection.
Immune cell counts were not useful predictors of infection risk. Functional assessment of stimulated PBMCs has identified potential immune profiles that may predict future infection risk in patients with RRMM.
多发性骨髓瘤（MM）患者感染风险增加。在基于免疫治疗的时代，感染风险的临床评估面临越来越大的挑战。开展了一项试点系统水平免疫分析研究，以确定感染的预测标志物。
对参加来那度胺和地塞米松治疗试验的复发和/或难治性MM（RRMM）患者进行评估。从临床记录中提取患者人口统计学、疾病和感染发作的数据。使用RNA测序和质谱流式细胞术（CyTOF），对在规定间隔收集的外周血单个核细胞（PBMC）进行分析，无论是否有丝裂原再刺激。比较发生感染和未发生感染的患者之间CyTOF衍生的细胞亚群和RNAseq基因表达谱，以确定在3个月内预测感染的免疫特征。
23名患者参加了原始治疗试验，我们能够获取17名RRMM患者的样本用于本研究的进一步评估。近一半的患者在样本采集后3个月内发生了感染（8/17）。感染大多通过临床诊断（62.5%），且大多数累及呼吸道（87.5%）。我们未检测到发生感染和未发生感染的患者之间免疫细胞群体的表型或数量差异。对刺激后的PBMC进行转录谱分析发现，发生感染的患者具有独特的Th2免疫途径特征。
免疫细胞计数并非感染风险的有效预测指标。对刺激后的PBMC进行功能评估已确定了可能预测RRMM患者未来感染风险的潜在免疫特征。
