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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 non-improvers 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.

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