Temporal Evolution of Functional Immune Reconstitution after Allogeneic HSCT.

Area of Science:

• Immunology
• Transplantation Science
• Genomics

Background:

• Immune reconstitution (IR) post-allogeneic hematopoietic stem cell transplantation (allo-HSCT) is typically monitored by immune cell counts.
• This quantitative approach may not fully reflect the immune system's functional capacity.

Purpose of the Study:

• To evaluate the temporal evolution of functional IR in allo-HSCT recipients.
• To compare functional immune profiles with traditional immune cell counts.

Main Methods:

• Whole-blood stimulation assays (TruCulture) with LPS or SEB were performed on 55 allo-HSCT recipients and 10 healthy volunteers.
• Gene expression of 144 immune-related genes was quantified using NanoString technology at 6 and 12 months post-transplant.
• Functional immune profiles were analyzed over time, correlated with demographics, clinical characteristics, and cell counts.

Main Results:

• A discrepancy was observed between quantitative and qualitative immune assessments.
• While CD4+ T cell counts improved in recipients (25% to 46%), transcriptomic profiles showed persistent functional alterations, with over 78% of under-expressed genes at 6 months remaining so at 12 months.
• Transcriptomic profiling revealed functional outcomes linked to clinical characteristics not evident from cell counts alone.

Conclusions:

• Quantitative assessment of immune effectors alone is insufficient for classifying allo-HSCT recipients' functional immune capacity.
• Immune functional assays (IFA) provide a comprehensive understanding of functional IR post-allo-HSCT.
• IFA can facilitate personalized post-transplant management.