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The innate immune response in HIV/AIDS septic shock patients: a comparative study.

ABSTRACT:

Introduction

In recent years, the incidence of sepsis has increased in critically ill HIV/AIDS patients, and the presence of severe sepsis emerged as a major determinant of outcomes in this population. The inflammatory response and deregulated cytokine production play key roles in the pathophysiology of sepsis; however, these mechanisms have not been fully characterized in HIV/AIDS septic patients.

Methods

We conducted a prospective cohort study that included HIV/AIDS and non-HIV patients with septic shock. We measured clinical parameters and biomarkers (C-reactive protein and cytokine levels) on the first day of septic shock and compared these parameters between HIV/AIDS and non-HIV patients.

Results

We included 30 HIV/AIDS septic shock patients and 30 non-HIV septic shock patients. The HIV/AIDS patients presented low CD4 cell counts (72 [7-268] cells/mm(3)), and 17 (57%) patients were on HAART before hospital admission. Both groups were similar according to the acute severity scores and hospital mortality. The IL-6, IL-10 and G-CSF levels were associated with hospital mortality in the HIV/AIDS septic group; however, the CRP levels and the surrogates of innate immune activation (cytokines) were similar among HIV/AIDS and non-HIV septic patients. Age (odds ratio 1.05, CI 95% 1.02-1.09, p=0.002) and the IL-6 levels (odds ratio 1.00, CI 95% 1.00-1.01, p=0.05) were independent risk factors for hospital mortality.

Conclusions

IL-6, IL-10 and G-CSF are biomarkers that can be used to predict prognosis and outcomes in HIV/AIDS septic patients. Although HIV/AIDS patients are immunocompromised, an innate immune response can be activated in these patients, which is similar to that in the non-HIV septic population. In addition, age and the IL-6 levels are independent risk factors for hospital mortality irrespective of HIV/AIDS disease.

SUBMITTER: Amancio RT

PROVIDER: S-EPMC3708901 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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The innate immune response in HIV/AIDS septic shock patients: a comparative study.

Amancio Rodrigo T RT Japiassu Andre M AM Gomes Rachel N RN Mesquita Emersom C EC Assis Edson F EF Medeiros Denise M DM Grinsztejn Beatriz B Bozza Patrícia T PT Castro-Faria Neto Hugo C HC Bozza Fernando A FA

PloS one 20130711 7

<h4>Introduction</h4>In recent years, the incidence of sepsis has increased in critically ill HIV/AIDS patients, and the presence of severe sepsis emerged as a major determinant of outcomes in this population. The inflammatory response and deregulated cytokine production play key roles in the pathophysiology of sepsis; however, these mechanisms have not been fully characterized in HIV/AIDS septic patients.<h4>Methods</h4>We conducted a prospective cohort study that included HIV/AIDS and non-HIV ...[more]

PMID: 23874739

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Project description:BackgroundAdvancing age is a strong risk factor for adverse outcomes across multiple disease processes. However, septic surgical and trauma patients are unique in that they incur two or more inflammatory insults. The effects of advanced age on sepsis pathophysiology and outcomes remain unclear.MethodsWe performed a single-center, prospective observational cohort study of surgical intensive care unit patients with severe sepsis/septic shock. Peripheral blood was collected for genomic, cytokine, and biomarker analysis at 0.5 day, 1 day, 4 days, 7 days, 14 days, 21 days, and 28 days after sepsis onset. Based on sensitivity analysis, cohorts were defined as "young" (<55 years) and "aged" (≥55 years). We compared age-defined cohorts to determine differences in patient characteristics, biomarker profiles, and clinical outcomes.ResultsThe cohort included 173 patients with severe sepsis (n = 93; 53.8%) or septic shock (n = 80; 46.2%), with a mean age of 60.9 (±14.5) years. Intra-abdominal sepsis was the leading source (n = 81; 46.8%), followed by necrotizing soft tissue infection (n = 33, 19.1%) and pneumonia (n = 30; 17.3%). Aged patients had a higher comorbidity burden, but were otherwise similar to the young cohort. The aged cohort had a higher severity of early physiologic derangement (median APACHE II, 23 vs. 18; p = 0.002), greater incidence of multiple organ failure (64.3% vs. 40.4%, p = 0.006), and hospital mortality (15.9% vs. 2.1%; p = 0.016). Six-month mortality was significantly higher in the aged cohort as compared with young cohort (31% vs. 9%; p = 0.003). Aged septic patients biomarker trajectories suggestive of persistent immunosuppression (absolute lymphocyte count, soluble programed death ligand-1) and catabolism (Urine 3MH-Cr ratio, insulin growth factor, IGF1BP3, albumin) out to 28 days after sepsis.ConclusionAged, critically ill surgical patients have greater organ dysfunction and incidence of adverse clinical outcomes after sepsis. Biomarker profiles suggest an immunophenotype of persistent immunosuppression and catabolism. Advanced age may necessitate novel therapeutic strategies to promote multisystem organ recovery and improve survival after sepsis.Level of evidencePrognostic, level II.

Project description:Background: Septic shock, a major cause of death in critical care, is the clinical translation of a cytokine storm in response to infection. It can be complicated by sepsis-induced immunosuppression, exemplified by blood lymphopenia, an excess of circulating Treg lymphocytes, and decreased HLA-DR expression on circulating monocytes. Such immunosuppression is associated with secondary infections, and higher mortality. The effect of these biological modifications on circulating innate lymphoid cells (ILCs) has been little studied. Methods: We prospectively enrolled patients with septic shock (Sepsis-3 definition) in the intensive care unit (ICU) of Timone CHU Hospital. ICU controls (trauma, cardiac arrest, neurological dysfunction) were recruited at the same time (NCT03297203). We performed immunophenotyping of adaptive lymphocytes (CD3+ T cells, CD19+ B cells, CD4+CD25+FoxP3+ Treg lymphocytes), ILCs (CD3-CD56+ NK cells and helper ILCs - ILC1, ILC2, and ILC3), and monocytes by flow cytometry on fresh blood samples collected between 24 and 72 h after admission. Results: We investigated adaptive and innate circulating lymphoid cells in the peripheral blood of 18 patients in septic shock, 15 ICU controls, and 30 healthy subjects. As expected, the peripheral blood lymphocytes of all ICU patients showed lymphopenia, which was not specific to sepsis, whereas those of the healthy volunteers did not. Circulating CD3+ T cells and CD3-CD56+ NK cells were mainly concerned. There was a tendency toward fewer Treg lymphocytes and lower HLA-DR expression on monocytes in ICU patients with sepsis. Although the ILC1 count was higher in septic patients than healthy subjects, ILC2, and ILC3 counts were lower in both ICU groups. However, ILC3s within the total ILCs were overrepresented in patients with septic shock. The depression of immune responses has been correlated with the occurrence of secondary infections. We did not find any differences in ILC distribution according to this criterion. Conclusion: All ICU patients exhibit lymphopenia, regardless of the nature (septic or sterile) of the initial medical condition. Specific distribution of circulating ILCs, with an excess of ILC1, and a lack of ILC3, may characterize septic shock during the first 3 days of the disease.

Project description:Background: Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection. To date, no biomarker has shown sufficient evidence and ease of application in clinical routine to monitor the complexity of the sepsis-related immune alterations. Multiple levels of interaction of human endogenous retroviruses (HERVs) with the immune response led us to hypothesize that they may be relevant candidates both to contribute to the physiopathology of sepsis and to be part of a molecular signature. In this study, we used a recently described high-density microarray which allows exploring HERVs/MaLRs transcriptome in septic shock patients. Results: About 6.9% of the HERVs/MalRs repertoire is transcribed in whole blood. Concerning the functionality of LTRs, the majority of LTRs are silent (62.9%), 7.5% of LTRs present a putative constitutive promoter or polyA functions, while 20.4% of them may shift from silent to active. Evidence was given that a subset of HERVs/MaLRs and genes were modulated in septic shock patients according to the monocyte HLA-DR (mHLA-DR) expression level measured by flow cytometry, as a proxy of immunosuppression. We then identified a large signature consisting of 193 differentially expressed HERVs/MaLRs probesets further reduced to a smaller 10 HERVs/MaLRs signature. Both signatures, validated in an independent septic shock cohort, identified two groups of patients with different severity features including clinical criteria and the CD74 and CX3CR1 sepsis severity molecular markers. Conclusion: This microarray-based approach unveiled the expression of about 87,912 distinct HERV probesets and identified 764 putative promoter LTRs and 642 putative polyA LTRs in whole blood. HERV/MaLR expression was shown to be tightly modulated in septic shock patients according to mHLA-DR expression. We identified a set of potential molecular biomarkers in septic shock patients partially overlapping immunosuppression (mHLA-DR), and the risk of Health Care associated Infections (HAI) (CD74 ratio), complementary to existing molecular markers of a sepsis patients stratification. We identified a HERV/MaLR signature discriminating patients based on their immunosuppression state and severity.

Project description:BackgroundSepsis is a leading cause of mortality in intensive care units and vasoactive drugs are widely used in septic patients. The cardiovascular response of septic shock patients during resuscitation therapies and the relationship of the cardiovascular response and clinical outcome has not been clearly described.MethodsWe included adult patients admitted to the ICU with sepsis from Peking Union Medical College Hospital (internal), Medical Information Mart for Intensive Care IV (MIMIC-IV) and eICU Collaborative Research Database (eICU-CRD). The Blood Pressure Response Index (BPRI) was defined as the ratio between the mean arterial pressure and the vasoactive-inotropic score. BRRI was compared with existing risk scores on predicting in-hospital death. The relationship between BPRI and in-hospital mortality was calculated. A XGBoost's machine learning model identified the features that influence short-term changes in BPRI.FindingsThere were 2139, 9455, and 4202 patients in the internal, MIMIC-IV and eICU-CRD cohorts, respectively. BPRI had a better AUROC for predicting in-hospital mortality than SOFA (0.78 vs. 0.73, p = 0.01) and APS (0.78 vs. 0.74, p = 0.03) in the internal cohort. The estimated odds ratio for death per unit decrease in BPRI was 1.32 (95% CI 1.20-1.45) when BPRI was below 7.1 vs. 0.99 (95% CI 0.97-1.01) when BPRI was above 7.1 in the internal cohort; similar relationships were found in MIMIC-IV and eICU-CRD. Respiratory support and latest cumulative 12-h fluid balance were intervention-related features influencing BPRI.InterpretationBPRI is an easy, rapid, precise indicator of the response of patients with septic shock to vasoactive drugs. It is a comparable and even better predictor of prognosis than SOFA and APS in sepsis and it is simpler and more convenient in use. The application of BPRI could help clinicians identify potentially at-risk patients and provide clues for treatment.FundingFundings for the Beijing Municipal Natural Science Foundation; the National High Level Hospital Clinical Research Funding; the CAMS Innovation Fund for Medical Sciences (CIFMS) from Chinese Academy of Medical Sciences and the National Key R&D Program of China, Ministry of Science and Technology of the People's Republic of China.

Dataset Information

The innate immune response in HIV/AIDS septic shock patients: a comparative study.

Introduction

Methods

Results

Conclusions

Publications

The innate immune response in HIV/AIDS septic shock patients: a comparative study.

Similar Datasets

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