Predicting the Outcomes of Subjects With Severe Community-Acquired Pneumonia Using Monocyte Human Leukocyte Antigen-DR

Abstract

BACKGROUND:The objective was to study the level of monocyte-human leukocyte antigen-DR (mHLA-DR), an immune function-related biomarker, at 24 h after admission, to predict the outcomes of subjects with severe pneumonia. METHODS: Subjects with severe community-acquired pneumonia (n ‫؍‬ 102) were included in the study. Blood samples were collected from each subject 24 h after admission. Data regarding age, sex, P aO 2 /F IO 2 , comorbidities, occurrence of altered mental status, bacteremia, septic shock, Acute Physiology and Chronic Health Evaluation (APACHE) II score, and Sequential Organ Failure Assessment (SOFA) score within the first 24 h; the highest temperature within 24 h after admission; mechanical ventilation usage; timing of antibiotic therapy; ICU stay; and 28-d survival were collected. Expression of mHLA-DR was measured by flow cytometry. RESULTS: APACHE II score and SOFA score were significantly higher (P < .001), whereas the mHLA-DR expression was significantly lower (P < .001) in the non-survivors than in the survivors. The outcomes at day 28 after admission were significantly associated with the APACHE II score (P ‫؍‬ .002, odds ratio [OR] ‫؍‬ 1.27, 95% CI 1.10 -1.48), the SOFA score (P ‫؍‬ .003, OR ‫؍‬ 1.52, 95% CI 1.15-2.00), and mHLA-DR level (P ‫؍‬ .01, OR ‫؍‬ 0.91, 95% CI 0.85-0.98), as shown by logistic regression. The area under the receiver operating characteristic curve was 0.877 (95% CI 0.81-0.94, P < .001), 0.862 (95% CI 0.79 -0.93, P < .001), and 0.781 (95% CI 0.69 -0.87, P < .001) for APACHE II score, SOFA score, and the mHLA-DR expression, respectively. The optimal threshold for mHLA-DR level was 27.2%. Kaplan-Meier survival analysis showed that subjects with mHLA-DR > 27.2% had significantly better outcomes compared with < 27.2% level (P < .001, log rank test, hazard ratio ‫؍‬ 0.963, 95% CI 0.94 -0.99). CONCLUSIONS: mHLA-DR may be a reliable biomarker that can predict the outcomes of patients with severe community-acquired pneumonia, and 27.2% may be the cut-off value to predict the outcomes.

Simultaneous Depression of Immunological Synapse and Endothelial Injury is Associated with Organ Dysfunction in Community-Acquired Pneumonia

“…Depressed expression of HLA-DRA in monocytes and dendritic cells has been found in patients with sepsis, probably due to an increased apoptosis of lymphoid cells or T-cell exhaustion. Zhuang et al [9] reported that patients with mHLA-DR ≥27.2% had significantly better outcomes compared to those with levels of <27.2%. Inducible T cell co-stimulator (ICOS) is involved in directing effector T cell differentiation and has an important role in adaptive immunity [21].…”

“…In fact, sepsis [5] and ventilator-associated pneumonia (VAP) are characterized by the depression of the immunological synapse [6]. However, there is scarce information of immunological signatures at the transcriptomic level in CAP in non-critically ill patients, despite the fact that CAP is one of the most frequent infections causing sepsis [7,8] and that it has a potential association with endothelial damage [9].…”

Biomarkers in Pneumonia—Beyond Procalcitonin

“…In sepsis, the mHLA-DR decreases rapidly in correlation to the severity and outcome of the septic shock [94,95]. Zhuang et al [96] studied the expression of mHLA-DR by cytometry 24 h after admission to predict the 28-day survival of CAP patients. They reported that nonsurvivors significantly expressed reduced levels of mHLA-DR on their monocyte membranes [96].…”

“…Zhuang et al [96] studied the expression of mHLA-DR by cytometry 24 h after admission to predict the 28-day survival of CAP patients. They reported that nonsurvivors significantly expressed reduced levels of mHLA-DR on their monocyte membranes [96]. There is still not enough evidence whether mHLA-DR could be a useful marker in CAP.…”

Lymphopenic Community Acquired Pneumonia (L-CAP), an Immunological Phenotype Associated with Higher Risk of Mortality

“…In this regard, Davenport et al, using a transcriptomic analysis, found a gene expression signature (SRS1) which identifies individuals with an immunosuppressed phenotype and higher 14-day mortality within a cohort of patients with sepsis secondary to CAP ( Davenport et al, 2016 ). In addition, new biomarkers such as expression of HLA-DR on monocytes ( Zhuang et al, 2015 ), soluble CD14 (presepsin) ( Klouche et al, 2016 ), interleukins ( Menéndez et al, 2009 ; Andrijevic et al, 2014 ), procalcitonin ( Liu et al, 2016a ), and mid-regional pro-ADM ( Liu et al, 2016b ) could help risk assessment in the early stages of the disease. As an alternative to these new sophisticated (and expensive)“omics” and biomarker-based approaches, a simple leukogram has shown potential to be a tool for classifying patients with CAP or sepsis based on their outcomes.…”