Neutrophil-to-lymphocyte ratio as a surrogate for mHLA-DR in sepsis immunosuppression
Overview
This study demonstrates that the neutrophil-to-lymphocyte ratio (NLR) at day 7 post-ICU admission correlates with monocyte HLA-DR (mHLA-DR) levels, a reference biomarker for sepsis-induced immunosuppression. An NLR threshold >10 identifies patients with immunosuppressive features overlapping those with low mHLA-DR, suggesting NLR as a practical surrogate marker for immunosuppression in septic shock.
Background
Immuno-inflammatory alterations critically influence outcomes in septic shock, with immunosuppression increasing risks of ICU-acquired infections and mortality. Monocyte HLA-DR (mHLA-DR) is a validated biomarker for identifying immunosuppressed patients but is not widely available. There is a need for accessible surrogate markers derived from routine blood tests to guide immunomodulatory therapies. The neutrophil-to-lymphocyte ratio (NLR), calculated from standard leukocyte counts, may reflect both inflammation and immunosuppression.
Data Highlights
Parameter
Association
Threshold
AUC (ROC)
Concordance with mHLA-DR
NLR
Discriminates mHLA-DR < 8000 AB/C
>10
0.68 (p < 0.001)
64% in primary cohort; 75% in validation cohort
mHLA-DR
Immunosuppression biomarker
<8000 AB/C
Reference standard
NA
Immature neutrophils (CD10⁻CD16⁻)
Higher proportion in NLR > 10 patients
NA
NA
44% median overall; up to 73% in NLR > 10
Key Findings
NLR at day 7 post-ICU admission correlates significantly with mHLA-DR levels, with an optimal NLR threshold of 10 to identify immunosuppressed patients.
Patients with NLR > 10 exhibit features of immunosuppression including lymphopenia and increased immature neutrophils.
There is a 64% concordance between NLR > 10 and mHLA-DR < 8000 AB/C in the primary cohort, increasing to 75% in an independent validation cohort.
Patients classified as immunocompetent or immunosuppressed by either marker show similar baseline clinical characteristics.
NLR > 10 identifies patients in the “non-improvers” cluster with persistently low mHLA-DR and worse immunosuppressive profiles.
NLR is widely available from routine blood counts and may serve as a practical provisional marker to trigger further immunosuppression assessment.
Clinical Implications
Given its accessibility, NLR can be used as a provisional marker to identify septic patients at risk of immunosuppression who might benefit from immunostimulatory therapies. While it does not fully replace mHLA-DR measurement, NLR > 10 can serve as an alarm parameter prompting more detailed immune monitoring. Incorporation of NLR into clinical protocols could facilitate personalized immunomodulation in critical care settings.
Conclusion
NLR > 10 at day 7 post-septic shock admission integrates key immuno-inflammatory features and overlaps substantially with low mHLA-DR-defined immunosuppression. This readily available marker holds promise as a practical surrogate to guide immunotherapy pending further validation.
References
Personalized immunomodulation in critical illness, 2023 -- Immune trajectories and therapeutic timing
SOFA-2 score limitations, 2023 -- Lack of immuno-inflammatory parameters
mHLA-DR as immunosuppression biomarker, 2022 -- Clinical relevance and standardization
Validated mHLA-DR threshold and outcomes, 2023 -- ICU infections and mortality risk
Need for further validation of NLR, 2024 -- ICU populations and clinical thresholds
