Immunophenotyping of Septic Shock Patients with Endotheliopathy: Focus on Monocyte Subtypes and Immune regulatory molecules

Saif Al-Haidar¹Martin Schønemann-Lund²Mikkel Gybel-Brask³Jakob Stensballe⁴Lars Andresen¹Pär I. Johansson³Morten H. Bestle²Soren Skov^1*

• ¹University of Copenhagen, Copenhagen, Denmark
• ²Department of Anesthesia and Intensive Care, Copenhagen University Hospital - North Zealand, Hilleroed, Denmark
• ³Capital Region Blood Bank, Sect. for Transfusion Medicine, Department of Clinical Immunology, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark
• ⁴Department of Anesthesia, Surgery and Trauma Center, Copenhagen University Hospital, Copenhagen, Denmark

Septic shock is characterized by dysregulation of the host response to infection which results in life-threatening organ dysfunction that can be partly attributed to immune alterations and endothelial dysfunction (endotheliopathy). This lethal condition is dynamic, complex, and heterogeneous. Thus, an exploratory broad phenotypic and functional analysis of circulating immune cells and mediators were carried out to better understand the role of the immune system in a subgroup of septic shock patients with endotheliopathy defined by increased levels of soluble thrombomodulin (sTM). In this regard, especially the immune status of monocyte subtypes (classical, intermediate, and nonclassical) was investigated for surface thrombomodulin (TM), MHC class II molecules (HLA-DR, -DQ, and - DP) and immunomodulatory surface receptors (TREM-1, CD137, VISTA, HVEM and BTLA). Our comprehensive immunophenotypic analysis on a septic shock cohort with endotheliopathy identified distinct immune perturbation patterns that potentially can lead to novel treatment avenues in the management of this life-threatening condition.