Monocyte Human Leukocyte antigen-DR Research Articles

The spinal cord injury-induced immune deficiency syndrome: results of the SCIentinel study.

Infections are prevalent after spinal cord injury (SCI), constitute the main cause of death and are a rehabilitation confounder associated with impaired recovery. We hypothesize that SCI causes an acquired lesion-dependent (neurogenic) immune suppression as an underlying mechanism to facilitate infections. The international prospective multicentre cohort study (SCIentinel; protocol registration DRKS00000122; n = 111 patients) was designed to distinguish neurogenic from general trauma-related effects on the immune system. Therefore, SCI patient groups differing by neurological level, i.e. high SCI [thoracic (Th)4 or higher]; low SCI (Th5 or lower) and severity (complete SCI; incomplete SCI), were compared with a reference group of vertebral fracture (VF) patients without SCI. The primary outcome was quantitative monocytic Human Leukocyte Antigen-DR expression (mHLA-DR, synonym MHC II), a validated marker for immune suppression in critically ill patients associated with infection susceptibility. mHLA-DR was assessed from Day 1 to 10 weeks after injury by applying standardized flow cytometry procedures. Secondary outcomes were leucocyte subpopulation counts, serum immunoglobulin levels and clinically defined infections. Linear mixed models with multiple imputation were applied to evaluate group differences of logarithmic-transformed parameters. Mean quantitative mHLA-DR [ln (antibodies/cell)] levels at the primary end point 84 h after injury indicated an immune suppressive state below the normative values of 9.62 in all groups, which further differed in its dimension by neurological level: high SCI [8.95 (98.3% confidence interval, CI: 8.63; 9.26), n = 41], low SCI [9.05 (98.3% CI: 8.73; 9.36), n = 29], and VF without SCI [9.25 (98.3% CI: 8.97; 9.53), n = 41, P = 0.003]. Post hoc analysis accounting for SCI severity revealed the strongest mHLA-DR decrease [8.79 (95% CI: 8.50; 9.08)] in the complete, high SCI group, further demonstrating delayed mHLA-DR recovery [9.08 (95% CI: 8.82; 9.38)] and showing a difference from the VF controls of -0.43 (95% CI: -0.66; -0.20) at 14 days. Complete, high SCI patients also revealed constantly lower serum immunoglobulin G [-0.27 (95% CI: -0.45; -0.10)] and immunoglobulin A [-0.25 (95% CI: -0.49; -0.01)] levels [ln (g/l × 1000)] up to 10 weeks after injury. Low mHLA-DR levels in the range of borderline immunoparalysis (below 9.21) were positively associated with the occurrence and earlier onset of infections, which is consistent with results from studies on stroke or major surgery. Spinal cord injured patients can acquire a secondary, neurogenic immune deficiency syndrome characterized by reduced mHLA-DR expression and relative hypogammaglobulinaemia (combined cellular and humoral immune deficiency). mHLA-DR expression provides a basis to stratify infection-risk in patients with SCI.

Immune Profiling Panel Gene Set Identifies Critically Ill Patients With Low Monocyte Human Leukocyte Antigen-DR Expression: Preliminary Results From the REAnimation Low Immune Status Marker (REALISM) Study.

There is a crucial unmet need for biomarker-guided diagnostic and prognostic enrichment in clinical trials evaluating immune modulating therapies in critically ill patients. Low monocyte expression of human leukocyte antigen-DR (mHLA-DR), considered as a reference surrogate to identify immunosuppressed patients, has been proposed for patient stratification in immunostimulation approaches. However, its widespread use in clinic has been somewhat hampered by technical constraints inherent to flow cytometry technology. The objective of the present study was to evaluate the ability of a prototype multiplex polymerase chain reaction tool (immune profiling panel [IPP]) to identify immunosuppressed ICU patients characterized by a low mHLA-DR expression. Retrospective observational cohort study. Adult ICU in a University Hospital, Lyon, France. Critically ill patients with various etiologies enrolled in the REAnimation Low Immune Status Marker study (NCT02638779). None. mHLA-DR and IPP data were obtained from 1,731 blood samples collected from critically ill patients with various etiologies and healthy volunteers. A partial least square regression model combining the expression levels of IPP markers was trained and used for the identification of samples from patients presenting with evidence of immunosuppression, defined here as mHLADR less than 8,000 antibodies bound per cell (AB/C). The IPP gene set had an area under the receiver operating characteristic curve (AUC) of 0.86 (95% CI 0.83-0.89) for the identification of immunosuppressed patients. In addition, when applied to the 123 patients still in the ICU at days 5-7 after admission, IPP similarly enriched the number of patients with ICU-acquired infections in the immunosuppressed group (26%), in comparison with low mHLA-DR (22%). This study reports on the potential of the IPP gene set to identify ICU patients presenting with mHLA-DR less than 8,000 AB/C. Upon further optimization and validation, this molecular tool may help in the stratification of patients that could benefit from immunostimulation in the context of personalized medicine.

Persistently Elevated Soluble Triggering Receptor Expressed on Myeloid Cells 1 and Decreased Monocyte Human Leucocyte Antigen DR Expression Are Associated With Nosocomial Infections in Septic Shock Patients.

Observational study. University Hospital in France. One hundred sixteen adult septic shock patients as a post hoc study from the IMMUNOSEPSIS cohort (NCT04067674). None. Plasma sTREM-1 and monocyte HLA-DR were measured at day 1 or 2 (D1/D2), D3/D4, and D6/D8 after admission. Associations with nosocomial infection were evaluated through multivariable analyses. At D6/D8, both markers were combined, and association with increased risk of nosocomial infection was evaluated in the subgroup of patients with most deregulated markers in a multivariable analysis with death as a competing risk. Significantly decreased mHLA-DR at D6/D8 and increased sTREM-1 concentrations were measured at all time points in nonsurvivors compared with survivors. Decreased mHLA-DR at D6/D8 was significantly associated with increased risk of secondary infections after adjustment for clinical parameters with a subdistribution hazard ratio of 3.61 (95% CI, 1.39-9.34; p = 0.008). At D6/D8, patients with persistently high sTREM-1 and decreased mHLA-DR presented with a significantly increased risk of infection (60%) compared with other patients (15.7%). This association remained significant in the multivariable model (subdistribution hazard ratio [95% CI], 4.65 [1.98-10.9]; p < 0.001). In addition to its prognostic interest on mortality, sTREM-1, when combined with mHLA-DR, may help to better identify immunosuppressed patients at risk of nosocomial infections.

Role of immunosuppression in an antibiotic stewardship intervention and its association with clinical outcomes and antibiotic use: protocol for an observational study (RISC-sepsis)

IntroductionSepsis is characterised by a dysregulated immune response to infection, with exaggerated pro-inflammatory and anti-inflammatory responses. A predominant immunosuppressive profile affecting both innate and adaptive immune responses is associated with...

Nocturnal urine 6-hydroxy sulfate melatonin is associated with the outcome of subjects with sepsis

Abstract Background It is imperative to identify potential biomarkers for early diagnosis and intervention of severe sepsis. This study investigated the relationship between melatonin secretion and outcome of sepsis after 28-day admission. Methods Patients with sepsis were randomly divided into an eye mask group and a control group. Blood and urine samples were collected from day 0 to 4. Relevant clinical data and 28-day survival data were obtained. Serum melatonin and urine 6-hydroxy sulfate melatonin (6-SMT) levels were measured. Results The outcome of sepsis did not differ between the eye mask and control groups. Acute Physiology and Chronic Health Evaluation (APACHE) II and Sequential Organ Failure Assessment (SOFA) scores were significantly higher and monocyte human leukocyte antigen-DR (mHLA-DR), serum melatonin, nocturnal urine 6-SMT, and 24-hour urine 6-SMT levels were significantly lower in the nonsurvivors than in the survivors. The outcome at day 28 after admission was significantly associated with APACHE II and SOFA scores and mHLA-DR, nocturnal urine 6-SMT, and 24-hour urine 6-SMT levels. The areas under the receiver operating characteristic curve were 0.785, 0.740, 0.774, and 0.858 for APACHE II score, SOFA score, mHLA-DR expression, and nocturnal urine 6-SMT amount, respectively. The optimal thresholds for mHLA-DR and nocturnal urine 6-SMT were 30.13% and 43.60%, respectively. Nocturnal urine 6-SMT level was significantly and positively correlated with mHLA-DR expression. Conclusion Nocturnal urine 6-SMT level may be a feasible biomarker to predict the outcome of patients with sepsis. The use of a night-time eye mask has no significant effect on the outcome of sepsis. Clinical trials This study was registered at clinicaltrials.gov (NCT02304224).

Impaired Lymphocyte Responses in Pediatric Sepsis Vary by Pathogen Type and are Associated with Features of Immunometabolic Dysregulation.

Sepsis is the leading cause of death in hospitalized children worldwide. Despite its hypothesized immune-mediated mechanism, targeted immunotherapy for sepsis is not available for clinical use. To determine the association between longitudinal cytometric, proteomic, bioenergetic, and metabolomic markers of immunometabolic dysregulation and pathogen type in pediatric sepsis. Serial peripheral blood mononuclear cell (PBMC) samples were obtained from 14 sepsis patients (34 total samples) and 7 control patients for this observational study. Flow cytometry was used to define immunophenotype, including T cell subset frequency and activation state, and assess intracellular cytokine production. Global immune dysfunction was assessed by tumor necrosis factor-α (TNF-α) production capacity and monocyte human leukocyte antigen DR (HLA-DR) expression. Mitochondrial function was assessed by bulk respirometry. Plasma cytokine levels were determined via Luminex assay. Metabolites were measured by liquid chromatography-mass spectrometry. Results were compared by timepoint and pathogen type. Sepsis patients were older (15.9 years vs. 10.4 years, P = 0.02) and had higher illness severity by PRISM-III (12.0 vs. 2.0, P < 0.001) compared to controls; demographics were otherwise similar, though control patients were predominately male. Compared to controls, sepsis patients at timepoint 1 demonstrated lower monocyte HLA-DR expression (75% vs. 92%, P = 0.02), loss of peripheral of non-naïve CD4+ T cells (62.4% vs. 77.6%, P = 0.04), and reduced PBMC mitochondrial spare residual capacity (SRC; 4.0 pmol/s/106 cells vs. 8.4 pmol/s/106 cells, P = 0.01). At sepsis onset, immunoparalysis (defined as TNF-α production capacity < 200 pg/mL) was present in 39% of sepsis patients and not identified among controls. Metabolomic findings in sepsis patients were most pronounced at sepsis onset and included elevated uridine and 2-dehydrogluconate and depleted citrulline. Loss of peripheral non-naïve CD4+ T cells was associated with immune dysfunction and reduced cytokine production despite increased T cell activation. CD4+ T cell differentiation and corresponding pro- and anti-inflammatory cytokines varied by pathogen. Pediatric sepsis patients exhibit a complex, dynamic physiologic state characterized by impaired T cell function and immunometabolic dysregulation which varies by pathogen type.

Phenotypic and Kinetic Changes of Myeloid Lineage Cells in Innate Response to Chikungunya Infection in Cynomolgus Macaques.

Chikungunya (CHIKV) is an emerging worldwide viral threat. The immune response to infection can lead to protection and convalescence or result in long-term sequelae such as arthritis. Early innate immune events during acute infection have been characterized for some cell types, but more must be elucidated with respect to cellular responses of monocytes and other myeloid lineage cells. In addition to their roles in protection and inflammation resolution, monocytes and macrophages are sites for viral replication and may also act as viral reservoirs. These cells are also found in joints postinfection, possibly playing a role in long-term CHIKV-induced pathology. We examined kinetic and phenotypic changes in myeloid lineage cells, including monocytes, in cynomolgus macaques early after experimental infection with CHIKV. We found increased proliferation of monocytes and decreased proliferation of myeloid dendritic cells early during infection, with an accompanying decrease in absolute numbers of both cell types, as well as a simultaneous increase in plasmacytoid dendritic cell number. An increase in CD16 and CD14 was seen along with a decrease in monocyte Human Leukocyte Antigen-DR isotype expression within 3 days of infection, potentially indicating monocyte deactivation. A transient decrease in T cells, B cells, and natural killer cells correlated with lymphocytopenia observed during human infections with CHIKV. CD4+ T cell proliferation decreased in blood, indicating relocation of cells to effector sites. These data indicate CHIKV influences proliferation rates and kinetics of myeloid lineage cells early during infection and may prove useful in development of therapeutics and evaluation of infection-induced pathogenesis.

Reduced Monocyte Subsets, Their HLA-DR Expressions, and Relations to Acute Phase Reactants in Severe COVID-19 Cases.

Monocytes are one of the principal immune defense cells that encounter infectious agents. However, an essential role of monocytes has been shown in the spread of viruses throughout the human body. Considering this dilemma, this study aimed to evaluate monocyte subsets and Human Leukocyte Antigen-DR isotype (HLA-DR) expressions in clinical coronavirus disease 2019 (COVID-19) cases. This prospective, multicenter, case-control study was conducted with COVID-19 patients and healthy controls. The patient group was divided into two subgroups according to disease severity (severe and non-severe). Three monocyte subsets (classical, CL; intermediate, INT; non-classical, NC) were analyzed with flow cytometry upon the patients' hospital admission. A total of 42 patients with COVID-19 and 30 controls participated in this study. The patients' conditions were either severe (n = 23) or non-severe (n = 19). All patients' monocyte and HLA-DR expressions were decreased compared with the controls (p < 0.05). Per disease severity, all monocyte subsets were not significant with disease severity; however, the HLA-DR expressions of CL monocytes (p = 0.002) and INT monocytes (p = 0.025) were more decreased in the severe patient group. In patients with various clinical features, NC monocytes were more affected. Based on these results, NC monocytes were more decreased in acute COVID-19 cases, though related various clinics decreased all monocyte subsets in these patients. Decreased monocyte HLA expressions may be a sign of immune suppression in severe patients, even when the percentage of monocyte levels has not decreased yet.

Innate Immune System Response to Burn Damage-Focus on Cytokine Alteration.

In the literature, burns are understood as traumatic events accompanied by increased morbidity and mortality among affected patients. Their characteristic feature is the formation of swelling and redness at the site of the burn, which indicates the development of inflammation. This reaction is not only important in the healing process of wounds but is also responsible for stimulating the patient’s innate immune system. As a result of the loss of the protective ability of the epidermis, microbes which include bacteria, fungi, and viruses have easier access to the system, which can result in infections. However, the patient is still able to overcome the infections that occur through a cascade of cytokines and growth factors stimulated by inflammation. Long-term inflammation also has negative consequences for the body, which may result in multi-organ failure or lead to fibrosis and scarring of the skin. The innate immune response to burns is not only immediate, but also severe and prolonged, and some people with burn shock may also experience immunosuppression accompanied by an increased susceptibility to fatal infections. This immunosuppression includes apoptosis-induced lymphopenia, decreased interleukin 2 (IL-2) secretion, neutrophil storm, impaired phagocytosis, and decreased monocyte human leukocyte antigen-DR. This is why it is important to understand how the immune system works in people with burns and during infections of wounds by microorganisms. The aim of this study was to characterize the molecular pathways of cell signaling of the immune system of people affected by burns, taking into account the role of microbial infections.

Immune Dysfunction is Associated with Readmission in Survivors of Sepsis Following Infected Pancreatic Necrosis.

ObjectiveImmunosuppression is common in patients with infected pancreatic necrosis (IPN) and associated with morbidity and mortality. This study aimed to investigate the impact of immune status on mortality and readmission after hospital discharge in patients with IPN-related sepsis.MethodsIn this prospective observational study, eligible adult patients with IPN-related sepsis requiring ICU admission were included. Monocytic human leukocyte antigen DR (mHLA-DR), expression of regulatory T cells (Treg), and neutrophil CD88 (nCD88) were measured on the diagnosis of sepsis, ICU discharge, hospital discharge, and 15, 30, 60 days after hospital discharge. Logistic regression model was used to assess potential risk factors for readmission 60-days within the index discharge.ResultsA total of 53 patients were included, 13 died during hospitalization and one withdrew the consent soon after discharge. Among the survivors, a tendency of immune recovery was observed during the consecutive follow-ups, evidenced by the increased expression of mHLA-DR. Sixteen patients (41.03%) were readmitted within 60 days after the index discharge. In the multivariable regression model, APACHE II score when sepsis was diagnosed >9 and mHLA-DR at discharged <14,591 AB/C were found to be independent risk factors affecting readmission.ConclusionImmunosuppression is common in patients with IPN-related sepsis and can persist until two months after discharge. The compromised mHLA-DR level at discharge was associated with readmission within two months after discharge.

Monocyte human leukocyte antigen-DR but not \u03b2-d-glucan may help early diagnosing invasive Candida infection in critically ill patients

BackgroundPrecision medicine risk stratification is desperately needed to both avoid systemic antifungals treatment delay and over prescription in the critically ill with risk factors. The aim of the present study was to explore the combination of host immunoparalysis biomarker (monocyte human leukocyte antigen-DR expression (mHLA-DR)) and Candida sp wall biomarker β-d-glucan in risk stratifying patients for secondary invasive Candida infection (IC).MethodsProspective observational study. Two intensive care units (ICU). All consecutive non-immunocompromised septic shock patients. Serial blood samples (n = 286) were collected at day 0, 2 and 7 and mHLA-DR and β-d-glucan were then retrospectively assayed after discharge. Secondary invasive Candida sp infection occurrence was then followed at clinicians’ discretion.ResultsFifty patients were included, 42 (84%) had a Candida score equal or greater than 3 and 10 patients developed a secondary invasive Candida sp infection. ICU admission mHLA-DR expression and β-d-glucan (BDG) failed to predict secondary invasive Candida sp infection. Time-dependent cause-specific hazard ratio of IC was 6.56 [1.24–34.61] for mHLA-DR < 5000 Ab/c and 5.25 [0.47–58.9] for BDG > 350 pg/mL. Predictive negative value of mHLA-DR > 5000 Ab/c and BDG > 350 pg/mL combination at day 7 was 81% [95% CI 70–92].ConclusionsThis study suggests that mHLA-DR may help predicting IC in high-risk patients with septic shock. The added value of BDG and other fungal tests should be regarded according to the host immune function markers.

Up-to-date information on polymyxin B-immobilized fiber column direct hemoperfusion for septic shock.

Endotoxin adsorption therapy by polymyxin B-immobilized fiber column direct hemoperfusion (PMX-DHP) has been used for the treatment of septic shock patients. Endotoxin, an outer membrane component of Gram-negative bacteria, plays an important role in the pathogenesis of septic shock. Endotoxin triggers a signaling cascade for leukocytes, macrophage, and endothelial cells to secrete various mediators including cytokines and nitric oxide, leading to septic shock and multiple organ dysfunction syndrome. PMX-DHP directly adsorbed not only endotoxin but also monocytes and anandamide. It reduced blood levels of inflammatory cytokines such as interleukin (IL)-1, IL-6, tumor necrosis factor-alpha and IL-17A, adhesion molecules, plasminogen activator inhibitor 1, and high mobility group box-1. As a result, PMX-DHP increased blood pressure and reduced the dose of vasoactive-inotropic agents. PMX-DHP improved monocyte human leukocyte antigen-DR expression in patients with severe sepsis and septic shock. A post hoc analysis of EUPHRATES (Evaluating the Use of Polymyxin B Hemoperfusion in Randomized Controlled Trial of Adults Treated for Endotoxemia and Septic Shock) trial has shown that PMX-DHP significantly reduced 28-day mortality compared with the control group in septic shock patients with endotoxin activity assay level between 0.60 and 0.89. Longer duration of PMX-DHP may be another strategy to bring out the beneficial effects of PMX-DHP. Further studies are needed to confirm the efficacy of PMX-DHP treatment for septic shock.

Effects of age and comorbidities on serum levels of inflammatory markers in community-acquired pneumonia.

Studies have suggested that an inappropriate inflammatory response is a major cause of treatment failure and mortality in patients with community-acquired pneumonia (CAP). We aimed to determine the effect of age and comorbidities on serum inflammatory markers in CAP. We performed a prospective cohort study of adults hospitalized with CAP. For the purposes of this study, we compared patients according to comorbidities and age. Inflammatory markers were measured at hospital admission, focusing on acute phase proteins, cytokines and monocyte human leucocyte antigen DR (mHLA-DR) expression. In patients with chronic pulmonary disease (COPD), serum cytokines had significantly decreased levels of tumour necrosis factor (TNF)-α, interleukin (IL)-6 and mHLA-DR expression, as well as the C-reactive protein (CRP), compared with patients who had no comorbidities. Similarly, patients with chronic heart disease had a significantly reduced CRP levels and mHLA-DR expression, whereas patients with chronic kidney disease had significantly higher serum levels of procalcitonin and TNF-α. Lower procalcitonin, IL-6 and IL-10 levels, as well as mHLA-DR expression, were documented in older patients, but with no significant differences compared to younger patients. Multimorbidity in older patients was associated with significant lower levels of CRP and mHLA-DR expression. The circulating inflammatory markers to CAP have profiles that differ with age and underlying comorbidities. Multimorbidity in the elderly is also associated with lower serum levels of some inflammatory markers. Our findings suggest that inflammatory markers in CAP should be interpreted after considering age and comorbid conditions.

Chinese expert consensus on diagnosis and management of immunosuppression in sepsis

This expert consensus uses clinical research evidence to explain the mechanism, monitoring and evaluation of sepsis-induced immunosuppression, and treatment with immune stimulation from two aspects: innate immunity and acquired immunity, aiming to help clinicians better understand sepsis-induced immune depression and its clinical significance. Clinical data suggest that the immune dysfunction is critically involved in the occurrence and development of sepsis. Quantitative detection of monocyte human leukocyte antigen DR and lymphocyte count can be used as important indicators to reflect the innate immune and acquired immune dysfunction in patients with sepsis. Immunomodulation therapy includes medication to improve innate immunity and acquired immunity, and immune stimulation combined with anti-inflammatory response.

Human Leukocyte Antigen-DR Deficiency and Immunosuppression-Related End-Organ Failure in SARS-CoV2 Infection.

Human Leukocyte Antigen-DR Deficiency and Immunosuppression-Related End-Organ Failure in SARS-CoV2 Infection.

Monocytic Human Leukocyte Antigen DR Expression in Young Infants Undergoing Cardiopulmonary Bypass

Monocytic human leukocyte antigen DR (mHLA-DR) expression levels have been reported to be a marker of immunosuppression and a predictor of sepsis and mortality. There are, however, scant data regarding mHLA-DR monitoring in young infants after cardiopulmonary bypass. Our objectives were to investigate the kinetics of mHLA-DR expression and to determine whether mHLA-DR levels are associated with healthcare-associated infection (HAI) after cardiopulmonary bypass in young infants. mHLA-DR levels were analyzed by flow cytometry using a standardized method in 49 infants (<3months old) with congenital heart disease before andafter cardiopulmonary bypass. Results are expressedas the number of anti-HLA-DR antibodies per cell (AB/c). Postoperative mHLA-DR expression was reduced in all infants. Eleven patients (22%) developed HAI, and 4 patients (8%) died during the 30-day follow-up. mHLA-DR expression was significantly lower on postoperative day 4 in the HAI group compared with those who without HAI (3768 AB/c [range, 1938-6144] vs 13,230 AB/c [range, 6152-19,130], P= .014). Although mHLA-DR expression was associated with postoperative severity, mHLA-DR ≤4500 AB/c in the first 72 hours among patients with higher postoperative severity (extracorporeal membrane oxygenation and/or corticoids and/or delayed closure of sternum) was associated with occurrence of HAI in the univariate analysis (odds ratio, 6.3; 95% confidence interval, 1.0-38.7; P= .037). Cardiopulmonary bypass induces a profound decrease in mHLA-DR expression in young infants. Among patients with higher postoperative severity, low level of mHLA-DR in the early postoperative period is associated with the development of HAI.

Reduced Monocytic Human Leukocyte Antigen-DR Expression Indicates Immunosuppression in Critically Ill COVID-19 Patients.

BACKGROUND:The cellular immune system is of pivotal importance with regard to the response to severe infections. Monocytes/macrophages are considered key immune cells in infections and downregulation of the surface expression of monocytic human leukocyte antigen-DR (mHLA-DR) within the major histocompatibility complex class II reflects a state of immunosuppression, also referred to as injury-associated immunosuppression. As the role of immunosuppression in coronavirus disease 2019 (COVID-19) is currently unclear, we seek to explore the level of mHLA-DR expression in COVID-19 patients.METHODS:In a preliminary prospective monocentric observational study, 16 COVID-19–positive patients (75% male, median age: 68 [interquartile range 59–75]) requiring hospitalization were included. The median Acute Physiology and Chronic Health Evaluation-II (APACHE-II) score in 9 intensive care unit (ICU) patients with acute respiratory failure was 30 (interquartile range 25–32). Standardized quantitative assessment of HLA-DR on monocytes (cluster of differentiation 14+ cells) was performed using calibrated flow cytometry at baseline (ICU/hospital admission) and at days 3 and 5 after ICU admission. Baseline data were compared to hospitalized noncritically ill COVID-19 patients.RESULTS:While normal mHLA-DR expression was observed in all hospitalized noncritically ill patients (n = 7), 89% (8 of 9) critically ill patients with COVID-19–induced acute respiratory failure showed signs of downregulation of mHLA-DR at ICU admission. mHLA-DR expression at admission was significantly lower in critically ill patients (median, [quartiles]: 9280 antibodies/cell [6114, 16,567]) as compared to the noncritically ill patients (30,900 antibodies/cell [26,777, 52,251]), with a median difference of 21,508 antibodies/cell (95% confidence interval [CI], 14,118–42,971), P = .002. Reduced mHLA-DR expression was observed to persist until day 5 after ICU admission.CONCLUSIONS:When compared to noncritically ill hospitalized COVID-19 patients, ICU patients with severe COVID-19 disease showed reduced mHLA-DR expression on circulating CD14+ monocytes at ICU admission, indicating a dysfunctional immune response. This immunosuppressive (monocytic) phenotype remained unchanged over the ensuing days after ICU admission. Strategies aiming for immunomodulation in this population of critically ill patients should be guided by an immune-monitoring program in an effort to determine who might benefit best from a given immunological intervention.

Early Immunoparalysis Was Associated with Poor Prognosis in Elderly Patients with Sepsis: Secondary Analysis of the ETASS Study.

PurposeAlthough immune dysfunction has been investigated in adult septic patients, early immune status remains unclear. In this study, our primary aim was to assess early immune status in adult patients with sepsis stratified by age and its relevance to hospital mortality.Patients and MethodsA post hoc analysis of a multicenter, randomized controlled trial was conducted; 273 patients whose immune status was evaluated within 48 hours after onset of sepsis were enrolled. Early immune status was evaluated by the percentage of monocyte human leukocyte antigen-DR (mHLA-DR) in total monocytes within 48 hours after onset of sepsis and it was classified as immunoparalysis (mHLA-DR ≤30%) or non-immunoparalysis (>30%). Three logistic regression models were conducted to explore the associations between early immunoparalysis and hospital mortality. We also developed two sensitivity analyses to find out whether the definition of early immune status (24 hours vs 48 hours after onset of sepsis) and immunotherapy affect the primary outcome.ResultsOf the 181 elderly (≥60yrs) and 92 non-elderly (<60yrs) septic patients, 71 (39.2%) and 25 (27.2%) died in hospital, respectively. The percentage of early immunoparalysis in the elderly was twice of that in the non-elderly patients (32% vs 16%, p=0.006). For the elderly, hospital mortality was higher in the immunoparalysis ones than the non-immunoparalysis ones (53.4% vs 32.5%, p=0.009). But there was no significant difference in hospital mortality between immunoparalysis non-elderly patients and non-immunoparalysis non-elderly ones (33.5% vs 26.0%, p=0.541). By means of logistic regression models, we found that early immunoparalysis was independently associated with increased hospital mortality in elderly, but not in non-elderly patients. Sensitivity analysis further confirmed the definition of early immune status and immunotherapy did not affect the outcomes.ConclusionThe elderly were more susceptible to early immunoparalysis after onset of sepsis. Early immunoparalysis was independently associated with poor prognosis in elderly, but not in non-elderly patients.

NCD64, mHLA-DR: Sensitive Diagnostic Markers of Infection in Term Infants Receiving Antibiotic Treatment

The diagnosis of neonatal sepsis is difficult because of its nonspecific clinical pictures. Monocytic human leukocyte antigen–DR (mHLA-DR), neutrophil surface CD64 (nCD64) expressions and their ratio (SI), have been used to identify newborns with sepsis. However, there is a lack of studies investigating the expression of these markers in neonatal patients receiving antibiotic treatment. The main aims of the study are: to determine the sensitivity, specificity value of mHLA-DR and SI using the QuantiBRITE Anti HLA-DR/Anti-Monocyte, a Becton Dickinson novel reagent that standardizes flow cytometry values for diagnosing infection in term newborns receiving antibiotics; to define the optimal cutoff value of these markers using the receiver operating characteristics (ROC) curve. We determined mHLA-DR and nCD64 expressions in 44 term infants with sepsis receiving antibiotic treatment admitted to neonatal intensive care unit at National Children Hospital, Hanoi, Vietnam, between December 2019 and March 2020. mHLA-DR, nCD64 expressions were quantified on the admission day and the SI (mHLA-DR*100/nCD64) was calculated. We also measured mHLA-DR, nCD64 levels and SI in 17 non-sepsis control patients. Mean nCD64 expressions was significantly lower in septic patients than in controls (p = 0.004). By contract, mHLA-DR expression was notably higher in sepsis group. Sensitivity and specificity to detect sepsis using nCD64 was 73.5% and 88.2%, respectively, while for SI it was 91.2% and 100%, respectively. Specificity was highest for SI>17 (100%). Positive likelihood ratios were highest for nCD64 > 3427.4 ABC (88.2%). We found out that SI were beneficial for diagnosis of sepsis in neonatal patients receiving antibiotic whereas mHLA-DR was a marker of low diagnostic value. If further validated, the use of nCD64 and SI as infection markers should allow indication of antibiotic treatment. How to Cite this Article Pubmed Style Nguyen Thi Ngoc Tu, Le Thanh Hai, Truong Thi Mai Hong, Pham Thu Hien, Le Thi Ha, Doan Thi Mai Thanh. mHLA-DR: Sensitive Diagnostic Markers of Infection in Term Infants Receiving Antibiotic Treatment. SRP. 2020; 11(9): 1077-1081. doi:10.31838/srp.2020.9.154 Web Style Nguyen Thi Ngoc Tu, Le Thanh Hai, Truong Thi Mai Hong, Pham Thu Hien, Le Thi Ha, Doan Thi Mai Thanh. mHLA-DR: Sensitive Diagnostic Markers of Infection in Term Infants Receiving Antibiotic Treatment. http://www.sysrevpharm.org/?mno=28449 [Access: March 30, 2021]. doi:10.31838/srp.2020.9.154 AMA (American Medical Association) Style Nguyen Thi Ngoc Tu, Le Thanh Hai, Truong Thi Mai Hong, Pham Thu Hien, Le Thi Ha, Doan Thi Mai Thanh. mHLA-DR: Sensitive Diagnostic Markers of Infection in Term Infants Receiving Antibiotic Treatment. SRP. 2020; 11(9): 1077-1081. doi:10.31838/srp.2020.9.154 Vancouver/ICMJE Style Nguyen Thi Ngoc Tu, Le Thanh Hai, Truong Thi Mai Hong, Pham Thu Hien, Le Thi Ha, Doan Thi Mai Thanh. mHLA-DR: Sensitive Diagnostic Markers of Infection in Term Infants Receiving Antibiotic Treatment. SRP. (2020), [cited March 30, 2021]; 11(9): 1077-1081. doi:10.31838/srp.2020.9.154 Harvard Style Nguyen Thi Ngoc Tu, Le Thanh Hai, Truong Thi Mai Hong, Pham Thu Hien, Le Thi Ha, Doan Thi Mai Thanh (2020) mHLA-DR: Sensitive Diagnostic Markers of Infection in Term Infants Receiving Antibiotic Treatment. SRP, 11 (9), 1077-1081. doi:10.31838/srp.2020.9.154 Turabian Style Nguyen Thi Ngoc Tu, Le Thanh Hai, Truong Thi Mai Hong, Pham Thu Hien, Le Thi Ha, Doan Thi Mai Thanh. 2020. mHLA-DR: Sensitive Diagnostic Markers of Infection in Term Infants Receiving Antibiotic Reviews in Pharmacy, 11 (9), 1077-1081. doi:10.31838/srp.2020.9.154 Chicago Style Nguyen Thi Ngoc Tu, Le Thanh Hai, Truong Thi Mai Hong, Pham Thu Hien, Le Thi Ha, Doan Thi Mai Thanh. nCD64, mHLA-DR: Sensitive Diagnostic Markers of Infection in Term Infants Receiving Antibiotic Treatment. Systematic Reviews in Pharmacy 11 (2020), 1077-1081. doi:10.31838/srp.2020.9.154 MLA (The Modern Language Association) Style Nguyen Thi Ngoc Tu, Le Thanh Hai, Truong Thi Mai Hong, Pham Thu Hien, Le Thi Ha, Doan Thi Mai Thanh. nCD64, mHLA-DR: Sensitive Diagnostic Markers of Infection in Term Infants Receiving Antibiotic Treatment. Systematic Reviews in Pharmacy 11.9 (2020), 1077-1081. Print. doi:10.31838/srp.2020.9.154 APA (American Psychological Association) Style Nguyen Thi Ngoc Tu, Le Thanh Hai, Truong Thi Mai Hong, Pham Thu Hien, Le Thi Ha, Doan Thi Mai Thanh (2020) mHLA-DR: Sensitive Diagnostic Markers of Infection in Term Infants Receiving Antibiotic Reviews in Pharmacy, 11 (9), 1077-1081. doi:10.31838/srp.2020.9.154

Mitochondrial Dysfunction is Associated With an Immune Paralysis Phenotype in Pediatric Sepsis.

Immune dysregulation is a defining feature of sepsis, but the role for mitochondria in the development of immunoparalysis in pediatric sepsis is not known. We sought to determine if mitochondrial dysfunction measured in peripheral blood mononuclear cells (PBMCs) is associated with immunoparalysis and systemic inflammation in children with sepsis. Prospective observational study. Single-academic pediatric intensive care unit (PICU). One hundred sixty-one children with sepsis/septic shock and 18 noninfected PICU controls. Mitochondrial respiration in PBMCs, markers of immune function, and plasma cytokines were measured on days 1 to 2 (T1), 3 to 5 (T2), and 8 to 14 (T3) after sepsis recognition, and once for controls. Immunoparalysis was defined as whole-blood ex vivo lipopolysaccharide-induced tumor necrosis factor-alpha (TNF-α) ≤200 pg/mL or monocyte human leukocyte antigen-DR ≤30%. Mitochondrial respiration was lower in children with versus without immunoparalysis measured at the same timepoint. Mitochondrial respiration measured early (at T1 and T2) was also lower in those with immunoparalysis at T2 and T3, respectively. Although most patients with immunoparalysis exhibited low mitochondrial respiration, this metabolic finding was not specific to the immunoparalysis phenotype. Plasma cytokines, including IL-8, IL-10, TNF-α, and MCP-1, were highest in the subset of sepsis patients with immune paralysis or low mitochondrial respiration at T1. Children with sepsis had lower PBMC mitochondrial respiration when immunoparalysis was present compared with those without immunoparalysis. The subsets with immune paralysis and low mitochondrial respiration exhibited the highest levels of systemic inflammation.