Distinct Immune Reconstitution Profiles Captured by Immune Functional Assays at 6 Months Post Allogeneic Hematopoietic Stem Cell Transplantation

Autor: William Mouton, Anne Conrad, Vincent Alcazer, Mathilde Boccard, Maxime Bodinier, Guy Oriol, Fabien Subtil, Hélène Labussière-Wallet, Sophie Ducastelle-Lepretre, Fiorenza Barraco, Marie Balsat, Gaëlle Fossard, Karen Brengel-Pesce, Florence Ader, Sophie Trouillet-Assant
Rok vydání: 2023
Předmět:
Zdroj: Transplantation and Cellular Therapy. 29:94.e1-94.e13
ISSN: 2666-6367
Popis: 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.
Databáze: OpenAIRE