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Monocyte Trajectories Endotypes Are Associated With Worsening in Septic Patients
Maxime Bodinier1, Estelle Peronnet1, Karen Brengel-Pesce1
1EA 7426 "Pathophysiology of Injury-Induced Immunosuppression" (Université Claude Bernard Lyon 1 - Hospices Civils de Lyon - bioMérieux), Joint Research Unit HCL-bioMérieux, Immunology Laboratory & Anesthesia and Critical Care Medicine Department, Hospices Civils de Lyon, Edouard Herriot Hospital, Lyon, France.
Abstract:
Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. The immune system plays a key role in sepsis onset and remains dysregulated over time in a heterogeneous manner. Here, we decipher the heterogeneity of the first week evolution of the monocyte HLA-DR (mHLA-DR) surface protein expression in septic patients, a key molecule for adaptive immunity onset. We found and verified four distinctive trajectories endotypes in a discovery (n = 276) and a verification cohort (n = 102). We highlight that 59% of septic patients exhibit low or decreasing mHLA-DR expression while in others mHLA-DR expression increased. This study depicts the first week behavior of mHLA-DR over time after sepsis onset and shows that initial and third day mHLA-DR expression measurements is sufficient for an early risk stratification of sepsis patients. These patients might benefit from immunomodulatory treatment to improve outcomes. Going further, our study introduces a way of deciphering heterogeneity of immune system after sepsis onset which is a first step to reach a more comprehensive landscape of sepsis.
Insights
Sepsis patients show diverse immune responses. Researchers identified four distinct patterns in monocyte HLA-DR (mHLA-DR) expression during the first week, enabling early risk stratification and potential immunomodulatory treatment.
Area of Science:
- Immunology
- Critical Care Medicine
- Systems Biology
Background:
- Sepsis is a life-threatening condition characterized by organ dysfunction due to a dysregulated host response to infection.
- Immune system dysregulation is a hallmark of sepsis, exhibiting heterogeneous and evolving patterns over time.
- Monocyte human leukocyte antigen-DR (mHLA-DR) expression is a critical marker for adaptive immunity and immune cell function.
Purpose of the Study:
- To decipher the heterogeneity and temporal evolution of mHLA-DR expression in septic patients during the first week post-sepsis onset.
- To identify distinct patient endotypes based on mHLA-DR expression trajectories.
- To evaluate the utility of mHLA-DR measurements for early risk stratification in sepsis.
Main Methods:
- Analysis of mHLA-DR surface protein expression in two cohorts: a discovery cohort (n=276) and a verification cohort (n=102).
- Identification and validation of distinct mHLA-DR expression trajectories (endotypes) over the first week of sepsis.
- Correlation of mHLA-DR expression patterns with patient outcomes and potential for immunomodulatory treatment stratification.
Main Results:
- Four distinct endotypes of mHLA-DR expression trajectories were identified and validated.
- Approximately 59% of septic patients displayed low or decreasing mHLA-DR expression, while the remainder showed increased expression.
- Early measurements of mHLA-DR on the initial and third day post-sepsis onset were sufficient for early risk stratification.
Conclusions:
- The study reveals significant heterogeneity in immune responses during early sepsis, specifically in mHLA-DR expression patterns.
- Early mHLA-DR profiling can stratify sepsis patients into different risk groups, guiding potential therapeutic interventions.
- This approach offers a novel method for understanding immune system heterogeneity in sepsis, paving the way for personalized treatment strategies.
