Joint Research Unit Hospices Civils de Lyon-bioMérieux, Hospices Civils de Lyon, Lyon Sud Hospital, Pierre-Bénite, France; Virology and Human Pathology - Virpath Team, International Centre for Research in Infectiology (CIRI), Claude Bernard Lyon 1 University, Lyon, France.
Legionella Pathogenesis Team, International Centre for Research in Infectiology (CIRI), Claude Bernard Lyon 1 University, Lyon, France; Infectious and Tropical Diseases Department, Hospices Civils de Lyon, Croix-Rousse Hospital, Lyon, France; Claude Bernard Lyon I University, Villeurbanne, France.
Transplant Cell Ther. 2023 Feb;29(2):94.e1-94.e13. doi: 10.1016/j.jtct.2022.10.025. Epub 2022 Nov 3.
Immune reconstitution after allogeneic-hematopoietic-stem-cell transplantation (allo-HSCT) is a complex and individual process. In this cross-sectional study, whole-blood (WB) immune functional assay (IFA) was used to characterize immune function by assessing immune-related gene/pathway alterations. The usefulness of this tool in the context of infection, 6 months after transplantation, was evaluated. Sixty allo-HSCT recipients at 6 months after transplantation and 10 healthy volunteers (HV) were included. WB was stimulated in standardized TruCulture tubes using lipopolysaccharides and Staphylococcal enterotoxin B. Gene expression was quantified using a custom 144-gene panel using NanoString nCounter technology and analyzed using Ingenuity Pathway Analysis. The relationships between immune function and clinical characteristics, immune cell counts, and post-transplantation infections were assessed. Allo-HSCT recipients were able to activate similar networks of the innate and adaptive immune response compared to HV, with, nevertheless, a lower intensity. A reduced number and a lower expression of genes associated with immunoregulatory and inflammatory processes were observed in allo-HSCT recipients. The use of immunosuppressive treatments was associated with a protracted immune reconstitution revealed by transcriptomic immunoprofiling. No difference in immune cell counts was observed among patients receiving or not receiving immunosuppressive treatments using a large immunophenotyping panel. Moreover, the expression of a set of genes, including CCL3/CCL4, was significantly lower in patients with Herpesviridae reactivation (32%, 19/60), which once again was not identified using classical immune cell counts. Transcriptional IFA revealed the heterogeneity among allo-HSCT recipients with a reduced immune function, a result that could not be captured by circulating immune cell counts. This highlights the potential added value of this tool for the personalized care of immunocompromised patients.
异基因造血干细胞移植（allo-HSCT）后免疫重建是一个复杂且个体化的过程。在这项横断面研究中，采用全血（WB）免疫功能测定（IFA）通过评估免疫相关基因/通路改变来描述免疫功能。评估了该工具在移植后 6 个月感染背景下的实用性。纳入 60 例 allo-HSCT 移植后 6 个月的患者和 10 名健康志愿者（HV）。在标准化 TruCulture 管中使用脂多糖和葡萄球菌肠毒素 B 刺激 WB。使用定制的 144 基因面板通过 NanoString nCounter 技术定量基因表达，并使用 Ingenuity Pathway Analysis 进行分析。评估了免疫功能与临床特征、免疫细胞计数和移植后感染之间的关系。与 HV 相比，allo-HSCT 受者能够激活相似的固有和适应性免疫反应网络，但强度较低。观察到 allo-HSCT 受者中与免疫调节和炎症过程相关的基因数量减少和表达降低。免疫转录组学分析显示，使用免疫抑制治疗与免疫重建时间延长有关。使用大型免疫表型面板观察到接受或不接受免疫抑制治疗的患者之间的免疫细胞计数无差异。此外，一组基因（包括 CCL3/CCL4）的表达在疱疹病毒再激活患者中显著降低（32%，19/60），这在用经典免疫细胞计数方法时并未识别到。转录 IFA 揭示了具有免疫功能降低的 allo-HSCT 受者的异质性，这一结果无法通过循环免疫细胞计数来捕获。这突出了该工具在免疫功能低下患者个体化治疗中的潜在附加价值。
