Sepsis initially triggers a hyper-inflammatory state which often evolves to a subsequent hypo-inflammatory state (immune-paralysis).
Leukocyte activation occurs early during sepsis and is a key component of the hyper-inflammatory response to infection. This response includes a “storm” of cytokines released into the circulation and a cascade of immunologic events directed at containing and killing pathogens (1). In addition, simultaneous anti-inflammatory processes lead to durable immunosuppression and increased risk for secondary infections (3–5).
The current paradigm suggests that the majority of deaths in sepsis are caused by immunosuppression in the continuation of sepsis, leading to incomplete elimination of pathogenic bacteria or newly acquired secondary infections. In these cases, treatments with immune stimulating therapeutic agents, like IFNγ, G-CSF, or GM-CSF, have proven to be potentially beneficial. However, there is no clinical sign of immunosuppression.
The best marker for the monitoring of immune alterations in critically ill patients so far remains decreased HLA-DR expression on monocytes (9,10).
The expression of HLA-DR on circulating monocytes has been shown to be a biomarker of sepsis-induced immunosuppression, as presented in the graph, with 65% of total mortality at low levels of HLA-DR (8). Many published articles have presented a correlation between the lack of recovery of mHLA-DR expression over time and secondary infections in sepsis [6,7].
This finding highlights the importance of the timing of immune monitoring in regard to the expected homeostatic response and the phase of sepsis.
The use of the commercially available tests is limited as the test should be performed 2 h after blood sampling (or 4 h if stored at 4°C) and the limited availability of flow cytometer for continuous monitoring.
Accellix HLA-DR, a 25-minute automated test will be available in the EU by Q3/2016. Initial clinical data validates the ability of Accellix HLA-DR to reliably detect 5,000 HLA-DR molecules/cell, the established cutoff for immunosuppression. To date, Accellix HLA-DR has been able to detect expression levels as low as 1,800 molecules/cell.
The samples were run on the Accellix HLA-DR and compared to the commercial Becton Dickinson kit run on a standard laboratory flow cytometer (FACS) with population gating and data analysis by experienced personnel.
The comparison presented an R2 of 0.9. These results establish the diagnostic equivalence of the two methods.