Systems Analysis of Antigen Presenting Cells in Human Sepsis

NCT03788772 | Completed

• 2 other identifiers: APHP1800162018-A01934-51
• Study Type: interventional
• Target: 119
• Locations: 1 country
• Sites: 1

Brief Summary

Sepsis is a common life-threatening inflammatory response to infection and is the leading cause of death in the intensive care unit. Septic patients exhibit a complex immunosuppressive response affecting both innate and adaptive components of immunity, with a possible link to nosocomial infections. However, the molecular and cellular mechanisms resulting in secondary immunosuppression remain poorly understood, but may involve the antigen-presenting cells (APC, including dendritic cells and monocytes/macrophages) that link innate and adaptive immunity. Furthermore, the increasing phenotypic and functional heterogeneity of APC subsets raise the question of their respective role in sepsis. We propose to address the pathophysiologal role of APC using systems biology approaches in human sepsis. The objective is to go from low- to high-resolution analysis of APC subset diversity and underlying molecular and functional features in sepsis. The global objective will be reached through:

1. 1.Systematic description and phenotypic analysis of circulating APC subsets in sepsis
2. 2.Association of APC subsets distribution, phenotype and function with severe sepsis physiopathology and relevant clinical outcomes (ICU-acquired infections and death)
3. 3.High-resolution molecular profiling of circulating APC subsets using population level and single cell RNAseq.

Conditions

Sepsis; Acute Circulatory Failure

Keywords

dendritic cell; sepsis

Outcome Measures

Primary Outcomes (1)

• ICU-acquired infections (nosocomial infections)

  Infections not present at the time of ICU admission and diagnosed at least after 48 hours in the ICU

  up to 3 months after the inclusion

Secondary Outcomes (1)

• In-hospital death

  up to 3 months after the inclusion

Study Arms (1)

Adults patients hospitalized in ICU

EXPERIMENTAL

Adult patients hospitalized in the intensive care unit (ICU) for severe infections (sepsis and septic shock) or or non-septic shock (cardiogenic or hemorrhagic shock)

Other: Multiple blood sampling; Other: Simple blood sampling

Interventions

Multiple blood sampling OTHER

ICU septic and non-septic patients will be subjected to repeated blood samples at the following time-points: ICU admission, day 4/5, ICU and hospital discharge, 3 months. Patients exhibiting ICU-acquired infection will also be sampled at the time of diagnosis (up to 6 additional blood samples of 20 mL within 3 months = 120mL)

Adults patients hospitalized in ICU

Simple blood sampling OTHER

Healthy controls (blood donors and patients undergoing elective cataract surgery) will be subjected to one single blood sample of 20 mL.

Adults patients hospitalized in ICU

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ICU patients with severe infections (Sepsis-3 definitions):
• clinically or microbiologically documented infection and organ dysfunction graded as follows:
• Sepsis: increase in the Sequential Organ Failure Assessment (SOFA) score of 2 points or more.
• Septic shock: vasopressor requirement to maintain a mean arterial pressure ≥ 65mmHg and serum lactate level \> 2 mmol/L in the absence of hypovolemia
• ICU patients with non-septic acute circulatory failure:
• Cardiogenic shock: left ventricle systolic dysfunction (echocardiographic left ventricular ejection fraction \< 45%) and the need of vasopressor (norepinephrine at any dose and inotropic support (dobutamine ≥ 5 µg/kg/min or epinephrine at any dose) in the absence of patent infection.
• Severe hemorrhage: hypotension with acute blood loss requiring transfusion of at least four packed red cells within 24h and vasopressor support by norepinephrine or epinephrine at any dose.
• Healthy controls:
• Blood donors
• Patients undergoing elective cataract surgery

You may not qualify if:

• All ICU patients
• hematological malignancy (or significant history of bone marrow disease),
• HIV infection at any stage,
• any immunosuppressive drugs including corticosteroids ≥ 0.5 mg/kg equivalent prednisone per day for more 7 days,
• bone marrow or solid organ transplantation,
• leucopenia (\<1000/mm3) excepted if due to sepsis,
• pregnancy
• do-not-resuscitate order at ICU admission
• patients under legal protection regimen.
• Healthy controls
• history of inflammatory disease
• hematological malignancy (or significant history of bone marrow disease),
• HIV infection at any stage,
• any immunosuppressive drugs including corticosteroids ≥ 0.5 mg/kg equivalent prednisone per day for more 7 days,
• bone marrow or solid organ transplantation,

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead
• URC-CIC Paris Descartes Necker Cochin: collaborator

Study Sites (1)

Cochin Hospital, AP-HP

Paris, 75014, France

Location

Related Publications (1)

• Saichi M, Ladjemi MZ, Korniotis S, Rousseau C, Ait Hamou Z, Massenet-Regad L, Amblard E, Noel F, Marie Y, Bouteiller D, Medvedovic J, Pene F, Soumelis V. Single-cell RNA sequencing of blood antigen-presenting cells in severe COVID-19 reveals multi-process defects in antiviral immunity. Nat Cell Biol. 2021 May;23(5):538-551. doi: 10.1038/s41556-021-00681-2. Epub 2021 May 10.

  PMID: 33972731 BACKGROUND

MeSH Terms

Conditions

Sepsis; Shock

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Frédéric PENE, MD PhD

  Assistance Publique - Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

• Vassili SOUMELIS, MD PhD

  Assistance Publique - Hôpitaux de Paris

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 20, 2018
• First Posted: December 28, 2018
• Study Start: July 15, 2019
• Primary Completion: May 23, 2022
• Study Completion: August 24, 2022
• Last Updated: September 12, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)