Flow Cytometry Analysis of the Reactive Oxygen Species in Immature Granulocytes in Septic Patient

NCT ID: NCT03846596

Last Updated: 2020-04-08

Basic Information

• Recruitment Status: TERMINATED
• Total Enrollment: 34 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2019-03-26
• Study Completion Date: 2020-03-10

Brief Summary

Sepsis is life-threatening organ dysfunction caused by a dysregulated host response to infection. Early during sepsis course, immature neutrophils could be found in the bloodstream and may be less efficient than mature neutrophils in reactive oxygen species (ROS) production. ROS induce an oxidative stress for bacteria which can protect through the SOS response. The main objective is to evaluate the level of ROS produced in the early steps of sepsis by the immature neutrophils.

Detailed Description

Sepsis is life-threatening organ dysfunction caused by a dysregulated host response to infection. The immune system is activated by both pathogen-associated and host-derived molecular patterns. A strong response of neutrophils is engaged and both innate and adaptive immune system homeostasis are strongly affected. Neutrophils are able to produce high concentrations of inducible reactive oxygen species (ROS), leading to an oxidative stress. ROS can be released extracellularly at the site of infection or intracellularly in the phagolysosome. At early phase of sepsis, immature granulocytes are present in the bloodstream and could help to predict sepsis deterioration. However, it has also been shown that they are less efficient than mature granulocytes in ROS production and phagocytosis. ROS are potent stressors for bacteria and can directly or indirectly damage DNA. Bacteria can protect against DNA damage through the SOS response, which is a coordinated cellular response regulated by a repressor, LexA, and a sensor/activator, RecA. The bacterial SOS response is involved in acquisition of resistances to antibiotics through increasing frequencies of spontaneous mutations or increasing the expression of resistance and adaptation genes. The hypothesis that the low-level production of ROS by immature granulocytes in the early steps of sepsis could be beneficial for both the host, as a high level of ROS induce organ damage and dysfunction, and the pathogen, as low concentrations of ROS would be able to induce the SOS response allowing bacteria to enhance an adaptive response. The main objective it is to evaluate the level of ROS produced by the immature granulocytes in septic patient. Then, it will be assess if it could promote antibiotic resistance expression via SOS-induced integron gene cassette rearrangements.

Conditions

Sepsis

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Evaluated

An additional blood tube will be taken from patients hospitalized in intensive care or emergency department for acute sepsis

Additional blood tube

Intervention Type: BIOLOGICAL

Additional blood tube during care

Interventions

Additional blood tube

Additional blood tube during care

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• Adult patients hospitalized in ICU or ED for acute sepsis

Exclusion Criteria

• Immunosupressed patients
• Active cancer
• HIV
• Hematological or inflammatory diseases

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Limoges

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Thomas DAIX, MD

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Limoges

Locations

Limoges university Hospital

Limoges, , France

Countries

France

Other Identifiers

87RI18-0031 (SEPSIROS)

Identifier Type: -

Identifier Source: org_study_id