Monocyte HLA-DR Assessment by a Novel Point-of-Care Device Is Feasible for Early Identification of ICU Patients With Complicated Courses—A Proof-of-Principle Study

Abstract

Background: Critically ill patients, especially following trauma or extensive surgery, experience a systemic immune response, consisting of a pro-inflammatory as well as a counterbalancing anti-inflammatory response. Pro-inflammation is necessary for the initiation of homeostatic control and wound healing of the organism. However, when the counterbalancing mechanisms dominate, a condition of secondary immunodeficiency occurs, which renders the patient susceptible for opportunistic or secondary infections. However, the incidence of this condition is yet illusive.Methods: For a period of 3 months (May to July 2017), 110 consecutive patients admitted to the surgical ICU of the Heidelberg University Hospital, a tertiary university hospital, were enrolled in the study. Monocyte HLA-DR (mHLA-DR), a long-known surrogate of monocyte function, was assessed quantitatively once on admission utilizing a novel point-of-care flow cytometer with single-use cartridges (Accelix system). Patients were followed up for further 28 days and data on ICU stay, antibiotic therapy, microbiological findings, and mechanical ventilation were recorded. Statistical analysis was performed to evaluate the incidence of immunosuppression—defined by different thresholds—as well as its consequence in terms of outcome and clinical course.Results: Depending on the HLA-DR threshold applied for stratification (≤8,000/≤5,000/≤2,000 molecules/cell), a large group of patients (85.5/68.2/40.0%) already presented with a robust decrease of HLA-DR on admission, independent of the cause for critical illness. Analyzed for survival, neither threshold was able to stratify patients with a higher mortality. However, both thresholds of 2,000 and 5,000 were able to discriminate patients with longer ICU stay, ventilation time and duration of antibiotic therapy, as well as higher count of microbiological findings. Moreover, a mHLA-DR value ≤2,000 molecules/cell was associated with higher incidence of overall antibiotic therapy.Conclusion: Single assessment of mHLA-DR using a novel point-of-care flow cytometer is able to stratify patients according to their risk of a complicated course. Therefore, this device overcomes the technical boundaries for measuring cellular biomarkers and paves the way for future studies involving personalized immunotherapy to patients with a high immunological risk profile independent of their background.Trial Registration: German Clinical Trials Register; ID: DRKS00012348.

Monocyte distribution width (MDW) parameter as a sepsis indicator in intensive care units

“…In conclusion, changes in functional proprieties related to monocytes have been reported in early sepsis, when monocytes with the inflammatory phenotypes (CD14 + CD16 ++ ) increase in blood, and in the immunosuppression state of sepsis, when the expression of HLA-DR in monocytes is decreases [30][31][32]. MDW, a parameter that reflects a change in circulating monocytes volume in response to pro-inflammatory signals from infectious organisms referred to as pathogen-associated molecular patterns, can have potential clinical applications for early sepsis detection in hospital and ICU settings.…”

Dynamic LTR retrotransposon transcriptome landscape in septic shock patients

“…Even though mHLA-DR expression was not a gold standard for the prediction of immunosuppression status, no gold standard or clinical signs currently exist to accurately evaluate immunosuppression in the ICU. In addition, the decrease in mHLA-DR expression remains an independent predictor of bad outcomes after sepsis [7]. Indeed, HERV/MaLR identified under these conditions were able to define clusters of patients in a larger independent cohort, that were different in terms of severity criteria.…”

“…To date, HLA-DR expression in monocytes, measured by flow cytometry, is a well-accepted and beneficial marker for monitoring immune alterations in critically ill patients (sepsis, trauma, pancreatitis, surgery, and burns). The decreased expression of mHLA-DR has been repeatedly associated with mortality and secondary infections and therefore remains an independent predictor of a poor outcome after sepsis [4,[6][7][8][9][10].…”

Porcine Reproductive and Respiratory Syndrome Virus Promotes SLA-DR-Mediated Antigen Presentation of Nonstructural Proteins To Evoke a Nonneutralizing Antibody Response In Vivo

“…3A). Since human leukocyte antigen-DR (HLA-DR), the counterpart of SLA-DR in humans, is a major player responsible for foreign-antigen presentation and cross talk with CD4 ϩ T helper cells, which enables activation of the adaptive immune response (43,44), SLA-DR was selected for quantitative real-time PCR (qPCR) verification. Our data suggested that mRNA of both the ␣ chain and ␤ chain of SLA-DR is strongly inhibited by PRRSV replication in BMDCs during the time points analyzed (Fig.…”