Determination of immunological parameters and risk factors in terms of persistent inflammation, immunosuppression, and catabolism syndrome in sepsis patients

Halacli, B. Determination of Immunological Parameters and Risk Factors in Terms of Persistent Inflammation, Immunosuppression, and Catabolism Syndrome in Sepsis Patients. Hacettepe University, Institute of Health Science, Immunology Program, Master's Thesis, Ankara, 2024. Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated response to infection. This study aimed to investigate the temporal changes in immune cells associated with the dysregulated response described in sepsis, alongside the clinical course, and to assess the presence of Persistent Inflammation, Immunosuppression, and Catabolism Syndrome (PIICS), a recognized subset of sepsis. Seven patients diagnosed with sepsis or septic shock, according to the Sepsis-3 criteria and admitted to the intensive care unit, were included in the study. As a control group, blood samples were collected once from seven healthy individuals. For the patient group, peripheral blood samples were collected on days 0, 7, 14, and 28, as well as at discharge. Peripheral blood mononuclear cells (PBMCs) were isolated and stored at -80°C for further analysis. The study assessed lymphocyte subsets, focusing on follicular helper T cells (Tfh) and Th17 cells for pro-inflammatory responses, as well as granulocytic and monocytic myeloid-derived suppressor cells (MDSCs), regulatory T cells (Tregs), and regulatory B cells (Bregs) for anti-inflammatory evaluation. Compared to healthy individuals, patients with sepsis showed increased levels of PD-1 (0-7-14th day, p=0.004, p=0.003, p=0.046, respectively) associated with immunosuppression, while HLA-DR levels, critical for antigen presentation, were significantly reduced on day 14 (p=0.022). Furthermore, Th17 cell levels were significantly elevated (p=0.015) on day 0 in sepsis patients compared to healthy controls. During follow-up days, monocytic MDSC levels were consistently higher in patients compared to control individuals (days 0, 7, 14, 28, and discharge days; p=0.011, p=0.02, p=0.006, p=0.042, respectively). Additionally, a significant decrease in granulocytic MDSC levels was observed during day 14 (p=0.014) and discharge (p=0.012). These findings suggest that immune dysregulation persists in some patients even at discharge, with fluctuating patterns observed in others. The results highlight the need for long-term monitoring to adequately evaluate the immune resolution process in sepsis. Keywords: sepsis, immunology, chronic critical illness, immune dysregulation, immune resolution This thesis was supported as a "Rapid Support Project" by HUBAP within the scope of HUSEP, under project code THD-2023-20655.