Insufficient Nutrition and Mortality Risk in Septic Patients Admitted to ICU with a Focus on Immune Dysfunction

Immune dysfunction is seen both in sepsis patients and in those with malnutrition. This study aimed to determine whether insufficient nutrition and immune dysfunction have a synergistic effect on mortality in critically ill septic patients. We conducted a prospective observational study from adult sepsis patients admitted to intensive care units (ICUs) between August 2013 and June 2016. Baseline characteristics including age, gender, body mass index, NUTRIC, Acute Physiology and Chronic Health Evaluation (APACHE) II and Sequential Organ Failure Assessment (SOFA) scores were recorded. Immune dysfunction, defined by human leukocyte antigen DR (HLA-DR) expression, was tested at days 1, 3, and 7 of ICU admission. The study included 151 patients with sepsis who were admitted to the ICU. The 28-day survivors had higher day 7 caloric intakes (89% vs 73%, p = 0.042) and higher day 1-HLA-DR expression (88.4 vs. 79.1, p = 0.045). The cut-off points of day 7 caloric intake and day 1-HLA-DR determined by operating characteristic curves were 65.1% and 87.2%, respectively. Immune dysfunction was defined as patients with day 1-HLA-DR < 87.2%. Insufficient nutrition had no influence on survival outcomes in patients with immune dysfunction. However, patients with insufficient nutrition had poor prognosis when they were immune competent. Insufficient nutrition and immune dysfunction did not have a synergistic effect on mortality in critically ill septic patients.

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Myeloid phenotypes in severe COVID-19 predict secondary infection and mortality: a pilot study

Annals of Intensive Care ◽

10.1186/s13613-021-00896-4 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Clémence Marais ◽

Caroline Claude ◽

Nada Semaan ◽

Ramy Charbel ◽

Simon Barreault ◽

...

Keyword(s):

Critically Ill ◽

Host Response ◽

Secondary Infection ◽

Myeloid Cells ◽

Suppressor Cells ◽

Human Leukocyte ◽

Myeloid Derived Suppressor Cells ◽

Phenotypic Characteristics ◽

Leukocyte Antigen ◽

Hla Dr

Abstract Background De-regulated host response to severe coronavirus disease 2019 (COVID-19), directly referring to the concept of sepsis-associated immunological dysregulation, seems to be a strong signature of severe COVID-19. Myeloid cells phenotyping is well recognized to diagnose critical illness-induced immunodepression in sepsis and has not been well characterized in COVID-19. The aim of this study is to review phenotypic characteristics of myeloid cells and evaluate their relations with the occurrence of secondary infection and mortality in patients with COVID-19 admitted in an intensive care unit. Methods Retrospective analysis of the circulating myeloid cells phenotypes of adult COVID-19 critically ill patients. Phenotyping circulating immune cells was performed by flow cytometry daily for routine analysis and twice weekly for lymphocytes and monocytes subpopulations analysis, as well as monocyte human leukocyte antigen (mHLA)-DR expression. Results Out of the 29 critically ill adult patients with severe COVID-19 analyzed, 12 (41.4%) developed secondary infection and six patients died during their stay. Monocyte HLA-DR kinetics was significantly different between patients developing secondary infection and those without, respectively, at day 5–7 and 8–10 following admission. The monocytes myeloid-derived suppressor cells to total monocytes ratio was associated with 28- and 60-day mortality. Those myeloid characteristics suggest three phenotypes: hyperactivated monocyte/macrophage is significantly associated with mortality, whereas persistent immunodepression is associated with secondary infection occurrence compared to transient immunodepression. Conclusions Myeloid phenotypes of critically ill COVID-19 patients may be associated with development of secondary infection, 28- and 60-day mortality.

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

Anesthesia & Analgesia ◽

10.1213/ane.0000000000005044 ◽

2020 ◽

Vol 131 (4) ◽

pp. 993-999 ◽

Cited By ~ 6

Author(s):

Thibaud Spinetti ◽

Cedric Hirzel ◽

Michaela Fux ◽

Laura N. Walti ◽

Patrick Schober ◽

...

Keyword(s):

Human Leukocyte Antigen ◽

Critically Ill ◽

Human Leukocyte ◽

Leukocyte Antigen

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Sampling From the Proteome to the Human Leukocyte Antigen-DR (HLA-DR) Ligandome ProceedsViaHigh Specificity

Molecular & Cellular Proteomics ◽

10.1074/mcp.m115.055780 ◽

2016 ◽

Vol 15 (4) ◽

pp. 1412-1423 ◽

Cited By ~ 38

Author(s):

Geert P. M. Mommen ◽

Fabio Marino ◽

Hugo D. Meiring ◽

Martien C. M. Poelen ◽

Jacqueline A. M. van Gaans-van den Brink ◽

...

Keyword(s):

Human Leukocyte Antigen ◽

Human Leukocyte ◽

Leukocyte Antigen ◽

Hla Dr

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Human Leukocyte Antigen (HLA)-Linked Control of Susceptibility to Pulmonary Tuberculosis and Association with HLA-DR Types

The Journal of Infectious Diseases ◽

10.1093/infdis/148.4.676 ◽

1983 ◽

Vol 148 (4) ◽

pp. 676-681 ◽

Cited By ~ 85

Author(s):

S. P. N. Singh ◽

N. K. Mehra ◽

H. B. Dingley ◽

J. N. Pande ◽

M. C. Vaidya

Keyword(s):

Pulmonary Tuberculosis ◽

Human Leukocyte Antigen ◽

Human Leukocyte ◽

Leukocyte Antigen ◽

Hla Dr

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Increased CD69 and Human Leukocyte Antigen-DR Expression on T Lymphocytes in Insulin-Dependent Diabetes Mellitus of Long Standing

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jcem.83.6.4889 ◽

1998 ◽

Vol 83 (6) ◽

pp. 2204-2209 ◽

Cited By ~ 9

Author(s):

Alois Gessl ◽

Werner Waldhäusl

Keyword(s):

Diabetes Mellitus ◽

T Cells ◽

Human Leukocyte ◽

Insulin Dependent Diabetes Mellitus ◽

Dependent Diabetes Mellitus ◽

Cd4 Cells ◽

Cd8 Cells ◽

Leukocyte Antigen ◽

Hla Dr ◽

Insulin Dependent

To better define prevailing activation of circulating T cell subsets in insulin-dependent diabetes mellitus (IDDM) of recent onset (DM; n= 31; median age ± sd,, 28 ± 6.9 yr) and of long standing (DML; n = 27; age, 33 ± 10.4 yr; median duration of disease, 105 months), CD4+ and CD8+ T cells were analyzed to determine their naive and memory subsets as well as their expression of human leukocyte antigen (HLA)-DR, interleukin-2 receptor α-chain (CD25), and CD69 by three-color flow cytometry. Twenty-six healthy subjects (HS; age, 32.0 ± 8.2 yr) served as controls. No deviation was seen in either IDDM group compared to HS in CD25 expression on CD4+ or CD8+ cells or in their CD45RA+ or CD45RA− subsets. HLA-DR expression, however, was increased (P < 0.05) in total CD8+ cells and CD45RA+ cells, with CD45RA− CD8+ cells joining the prevailing pattern only in DML. Among CD4+ cells, increased expression of HLA-DR molecules was restricted to total and CD45RA− cells in DML. CD69 expression did not differ between IDDM and HS, but differed between DML (CD4+, CD8+, and CD45RA− CD4+) and DM only. In conclusion, our data demonstrate that HLA-DR expression in IDDM is restricted to memory cells (CD45RA−) among CD4+ cells in DML and is more markedly confined to naive (CD45RA+) than to memory CD8+ cells, whereas the early activation antigen CD69 is more readily expressed in DML than in DM. The observed activation of circulating T cells suggests an ongoing immune process in IDDM both at clinical manifestation and after long duration.

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

Annals of Intensive Care ◽

10.1186/s13613-021-00918-1 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Boris Jung ◽

Clément Le Bihan ◽

Pierre Portales ◽

Nathalie Bourgeois ◽

Thierry Vincent ◽

...

Keyword(s):

Septic Shock ◽

Human Leukocyte Antigen ◽

Critically Ill ◽

Human Leukocyte ◽

Candida Infection ◽

Added Value ◽

Leukocyte Antigen ◽

Candida Sp ◽

Invasive Candida Infection ◽

Risk Patients

Abstract Background Precision 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). Methods Prospective 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. Results Fifty 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]. Conclusions This 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.

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Application of Peak Glucose Range and Diabetes Status in Mortality Risk Stratification in Critically Ill Patients with Sepsis

Diagnostics ◽

10.3390/diagnostics11101798 ◽

2021 ◽

Vol 11 (10) ◽

pp. 1798

Author(s):

Kai-Yin Hung ◽

Yi-Hsuan Tsai ◽

Chiung-Yu Lin ◽

Ya-Chun Chang ◽

Yi-Hsi Wang ◽

...

Keyword(s):

Risk Stratification ◽

Critically Ill ◽

Glucose Level ◽

Mortality Risk ◽

Sofa Score ◽

Goodness Of Fit ◽

Human Leukocyte ◽

Kaplan Meier ◽

Hla Dr ◽

Diabetes Status

The effects of diabetes and glucose on the outcomes of patients with sepsis are somewhat conflicting. This retrospective study enrolled 1214 consecutive patients with sepsis, including a subpopulation of 148 patients with immune profiles. The septic patients were stratified according to their Diabetes mellitus (DM) status or peak glucose level (three-group tool; P1: ≤140 mg/dL, P2: 141–220 mg/dL, P3: >220 mg/dL) on day 1. Although the DM group had a lower hazard ratio (HR) for 90-day mortality compared to non-DM patients, the adjusted HRs were insignificant. The modified sequential organ failure assessment-glucose (mSOFA-g) score can predict 90-day survival in patients with and without diabetes (β = 1.098, p < 0.001; β = 1.202, p < 0.001). The goodness of fit of the mSOFA-g score was 5% higher than the SOFA score of the subgroup without diabetes. The SOFA score and human leukocyte antigen-D-related (HLA-DR) expression were comparable between the groups. The P3 group had lower HLA-DR expression on days 1 and 3 and a higher 90-day mortality. The three-group tool was useful for predicting 90-day mortality in patients with separate Kaplan-Meier survival curves and mortality HRs in the construction and validation cohorts. The peak glucose level, instead of diabetes status, can be used as an easy adjunctive tool for mortality risk stratification in critically ill septic patients.

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Human leukocyte antigen (HLA) DR4 is not associated with differences in overall survival (OS), progression free survival (PFS), or graft-vs-host-disease (GVHD) following allogeneic hematopoietic stem cell transplantation (allo HSCT) for myeloid malignancies

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.6552 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 6552-6552

Author(s):

S. Gupta ◽

C. Aggarwal ◽

T. Hahn ◽

S. Padmanabhan ◽

P. McCarthy ◽

...

Keyword(s):

Acute Gvhd ◽

Chronic Gvhd ◽

Human Leukocyte ◽

Progression Free Survival ◽

Hematopoietic Stem ◽

Myeloid Malignancies ◽

Leukocyte Antigen ◽

Hla Dr ◽

Gvhd Prophylaxis ◽

Total Body

6552 Background: HLA DR4 is associated with autoimmune disorders and with response to cyclosporine immunosuppression in T-cell Large Granular Lymphoproliferative Disorder (BJH 2003;123(3)). We have earlier reported association of DR 15 positivity with decreased acute GVHD (aGVHD) in patients undergoing allo HSCT for myeloid malignancies (Blood, 2005 Nov 10;Epub). Therefore we investigated the role of HLA DR4 on graft-versus-leukemia effect and GVHD in HLA-matched allo HSCT performed for myeloid malignancies. Methods: A retrospective review of 119 consecutive related and 48 consecutive unrelated allo HSCT patients (pts) treated between 1992 and 2003 at RPCI was performed to investigate the influence of HLA DR4 on OS, PFS and the incidence of grade 2–4 aGVHD and chronic GVHD (cGVHD). HLA DR B1 locus typing was determined by either molecular (n=108) or serologic (n=59) methods. The proportion of patients with one or two HLA DR4 antigens was 26% (43/167) which is similar to the range seen in general Caucasian population. Pt characteristics included: AML (n=84), CML (n=63), and MDS (n=20); median age 43 years (range 11–66); Male (n=104), Female (n=63); Caucasian (>95%); Total Body Irradiation (TBI) conditioning regimens (n=124); Busulfan (Bu)/Cyclophosphamide (Cy) (n=22), Bu/TBI (n=27), Cy/TBI (n=13), Etoposide/Cy/TBI (n=84), or other combinations (n=21). Results: There was no difference in OS and the PFS between the HLA DR4 positive vs negative groups in any disease or donor subgroups (p=0.4 and 0.6). GVHD prophylaxis was similar in the two groups but aGVHD and cGVHD incidence was not different in the two groups (p=0.8 and 0.9) Conclusions: HLA DR 4 is not associated with differences in GVHD or outcomes unlike the previous finding that HLA DR15 is associated with decreased acute GVHD in myeloid malignancies. These results suggest that there are differential effects of HLA DR antigens on the incidence of GVHD and outcomes in myeloid and lymphoid malignancies. Understanding these differences may facilitate the design of pt specific GVHD prophylaxis following allo HSCT. No significant financial relationships to disclose.

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Detection of Dimers of Dimers of Human Leukocyte Antigen (HLA)–DR on the Surface of Living Cells by Single-Particle Fluorescence Imaging

The Journal of Cell Biology ◽

10.1083/jcb.140.1.71 ◽

1998 ◽

Vol 140 (1) ◽

pp. 71-79 ◽

Cited By ~ 52

Author(s):

Richard J. Cherry ◽

Keith M. Wilson ◽

Kathy Triantafilou ◽

Peter O'Toole ◽

Ian E.G. Morrison ◽

...

Keyword(s):

Human Leukocyte Antigen ◽

Fluorescence Imaging ◽

Mhc Class Ii ◽

Single Particle ◽

Human Leukocyte ◽

Living Cells ◽

Solid Substrate ◽

Oligomeric State ◽

Leukocyte Antigen ◽

Hla Dr

The technique of single-particle fluorescence imaging was used to investigate the oligomeric state of MHC class II molecules on the surface of living cells. Cells transfected with human leukocyte antigen (HLA)–DR A and B genes were labeled at saturation with a univalent probe consisting of Fab coupled to R-phycoerythrin. Analysis of the intensities of fluorescent spots on the cell surface revealed the presence of single and double particles consistent with the simultaneous presence of HLA-DR heterodimers and dimers of dimers. The proportion of double particles was lower at 37°C than at 22°C, suggesting that the heterodimers and dimers of dimers exist in a temperature-dependent equilibrium. These results are discussed in the context of a possible role for HLA-DR dimers of dimers in T cell receptor–MHC interactions. The technique is validated by demonstrating that fluorescence imaging can distinguish between dimers and tetramers of human erythrocyte spectrin deposited from solution onto a solid substrate. The methodology will have broad applicability to investigation of the oligomeric state of immunological and other membrane-bound receptors in living cells.

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