Monocytic HLA-DR expression kinetics in septic shock patients with different pathogens, sites of infection and adverse outcomes

Abstract

Background: Decreased monocytic (m)HLA-DR expression is the most studied biomarker of sepsis-induced immunosuppression. To date, little is known about the relationship between sepsis characteristics, such as the site of infection, causative pathogen, or severity of disease, and mHLA-DR expression kinetics. Methods: We evaluated mHLA-DR expression kinetics in 241 septic shock patients with different primary sites of infection and pathogens. Furthermore, we used unsupervised clustering analysis to identify mHLA-DR trajectories and evaluated their association with outcome parameters. Results: No differences in mHLA-DR expression kinetics were found between groups of patients with different sites of infection (abdominal vs. respiratory, p = 0.13; abdominal vs. urinary tract, p = 0.53) and between pathogen categories (Gram-positive vs. Gram-negative, p = 0.54; Gram-positive vs. negative cultures, p = 0.84). The mHLA-DR expression kinetics differed between survivors and non-survivors (p < 0.001), with an increase over time in survivors only. Furthermore, we identified three mHLA-DR trajectories ('early improvers', 'delayed or non-improvers' and 'decliners'). The probability for adverse outcome (secondary infection or death) was higher in the delayed or nonimprovers and decliners vs. the early improvers (delayed or non-improvers log-rank p = 0.03, adjusted hazard ratio 2.0 [95% CI 1.0-4.0], p = 0.057 and decliners log-rank p = 0.01, adjusted hazard ratio 2.8 [95% CI 1.1-7.1], p = 0.03). Conclusion: Sites of primary infection or causative pathogens are not associated with mHLA-DR expression kinetics in septic shock patients. However, patients showing delayed or no improvement in or a declining mHLA-DR expression have a higher risk for adverse outcome compared with patients exhibiting a swift increase in mHLA-DR expression. Our study signifies that changes in mHLA-DR expression over time, and not absolute values or static measurements, are of clinical importance in septic shock patients.

Combination of Monocyte Human Leukocyte Antigen-DR and β-d-Glucan for the Early Diagnosis of Invasive Candida Infection in Critically Ill Patients: A Proof of Concept Study

“…Invasive candida infection commonly appears in highly immunosuppressed patients and lower value of mHLA-DR could be associated with higher risk of ICI. Continuing or declining immune de ciency is associated with an increased mortality [32]. Similarly, our results suggest an increased probability of ICI when mHLA-DR remains < 5000 Ab/c after day 7 of septic shock.…”

“…Our population is mainly patients with sepsis related to peritonitis. Leijte et al found median mHLA-DR over 6000 Ab/c in bacterial peritonitis [32]. Invasive candida infection commonly appears in highly immunosuppressed patients and lower value of mHLA-DR could be associated with higher risk of ICI.…”

COVID-19 patients exhibit less pronounced immune suppression compared with bacterial septic shock patients

“…Although mHLA-DR expression levels in COVID-19 patients were lower than those observed in healthy subjects (15,000-45,000 mAb/cell [5]), the extent of suppression was less pronounced than observed in bacterial septic shock patients (geometric mean [95% CI] of 11,860 [11,035-12,746] vs. 5211 [4904-5537] mAb/cell, respectively; p < 0.0001; Fig. 1a, sepsis data from [1]). mHLA-DR expression kinetics revealed no change over time (Fig.…”

“…Fig. 1 a mHLA-DR expression in patients with COVID-19 (n = 24, multiple timepoints) and bacterial septic shock (n = 241, days 1-2, 3-4, and/or 6-8 after onset of septic shock, obtained using the same methodology, data recently published [1]). Horizontal line indicates geometric mean.…”

“…Low monocytic (m)HLA-DR expression is the most widely used marker of innate immune suppression in critically ill patients. We recently showed that in bacterial septic shock patients, low mHLA-DR expression is prevalent and associated with the development of secondary infections [1]. At the end of March 2020, there were in excess of 800,000 confirmed cases of coronavirus disease 2019 (COVID-19) worldwide, of whom more than 12,000 from the Netherlands.…”