Immune cell energy use and function in critically ill patients with sepsis

AI summary

From the trial's eligibility criteria. Machine-read from the registry text on this page, so it can be wrong. The registry text below and the trial team decide who can take part.

The trial is looking for adults in intensive care, with or without sepsis (a severe body reaction to infection), and healthy volunteers. It studies immune cells called γδ T cells.

Age

18 Years to 80 Years

Sex

All sexes

Disease stage

Three groups. Healthy volunteers with no acute or chronic major disease. ICU patients who are critically ill without sepsis by the Sepsis-3 criteria. ICU patients who meet the Sepsis-3 criteria (infection + ΔSOFA ≥ 2 points).

Earlier treatment

People cannot join if they had T-cell-targeted immune-suppressing treatment before ICU admission or within 24 hours after it. Examples: antithymocyte globulin, calcineurin inhibitors, mycophenolate mofetil, methotrexate, or corticosteroids >1 mg/kg/day prednisone equivalent. Also immune checkpoint inhibitors (anti-PD-1/PD-L1/CTLA-4) within the past 6 weeks.

Main reasons for not taking part

• Known immune deficiency, HIV infection or active blood cancer
• Stem cell or solid organ transplant within the past 3 months
• Expected ICU stay < 24 hours or very close to death
• Pregnancy or breastfeeding
• Active major bleeding

The registry criteria, word for word

Check if you might fit

Answer for yourself. This is not a decision: only the study team can say whether you can take part.

• Are you between 18 and 80 years old?YesNo

What the trial wants to find out

This prospective observational cohort study investigates the subset-specific metabolic adaptation and functional remodeling of cytotoxic γδ T cells in critically ill patients with and without sepsis. As a bridge between innate and adaptive immunity, γδ T cells contribute to early antimicrobial defense; however, their cytotoxic function and its metabolic regulation in sepsis remain incompletely understood. Our preliminary single-cell transcriptomic analysis revealed altered expression of cytotoxicity-associated genes (GZMB, PRF1, and GNLY) and mitochondrial oxidative phosphorylation (OXPHOS) pathway genes in cytotoxic γδ T cells from patients with sepsis. In particular, COX6C expression correlated with cytotoxic effector gene expression. Across healthy volunteers, critically ill non-septic patients, and critically ill septic patients, we will integrate flow cytometry, mitochondrial function assays, and functional validation experiments to characterize circulating cytotoxic γδ T-cell abundance and function and examine the contribution of COX6C to mitochondrial dysfunction and impaired cytotoxicity.

The 3 groups in the trial

• Healthy Controls (NHCs)

  Healthy volunteers without acute or chronic major diseases, aged ≥18 years, who have provided written informed consent. Participants undergo a single blood draw and rectal swab collection.

• Critically Ill Non-Septic Patients (CI-NS)

  Patients admitted to the ICU meeting the criteria for critical illness but without sepsis, as determined by the Sepsis-3 criteria (infection with ΔSOFA ≥ 2 points excluded). Participants are aged ≥18 years, with informed consent obtained from the patient or legally authorized representative. Blood and rectal swab samples are collected at three time points: within 24 hours of ICU admission (D0), Day 2 (D2), and Day 7 (D7). Clinical follow-up extends to 90 days.

• Critically Ill Septic Patients (CI-Sep)

  Patients admitted to the ICU meeting the Sepsis-3 criteria (infection with ΔSOFA ≥ 2 points). Participants are aged ≥18 years, with informed consent obtained from the patient or legally authorized representative. Blood and rectal swab samples are collected at three time points: within 24 hours of ICU admission (D0), Day 2 (D2), and Day 7 (D7). Clinical follow-up extends to 90 days.