Dynamics of monocytic HLA-DR expression differs between bacterial etiologies during the course of bloodstream infection

Cajander, Sara; Rasmussen, Gunlög; Tina, Elisabet; Magnuson, Anders; Söderquist, Bo; Källman, Jan; Strålin, Kristoffer

doi:10.1371/journal.pone.0192883

Cited by 22 publications

(26 citation statements)

References 35 publications

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“…Patients with an E. coli infection had expression levels similar to those found in healthy volunteers [11]. However, the population was heterogeneous and the observed differences might therefore be explained by the large differences in disease severity between patients in the different pathogen categories [11]. In the current cohort of septic shock patients, we do not find differences in mHLA-DR expression kinetics between patients with Gram-positive, Gram-negative and negative cultures.…”

Section: Discussionsupporting

confidence: 54%

“…Previous work revealed that, in patients with bloodstream infections, those with S. pneumonia infections showed a swift increase in mHLA-DR expression over and p values were calculated using repeated measures two-way ANOVA on log-transformed data vs. reference trajectory A (time*group interaction term). ***p < 0.001 calculated with one-way ANOVA on log-transformed data with Dunnett's multiple comparison test compared to baseline time, whereas patients with a S. aureus infection displayed a delayed recovery [11]. Patients with an E. coli infection had expression levels similar to those found in healthy volunteers [11].…”

Section: Discussionmentioning

confidence: 96%

“…***p < 0.001 calculated with one-way ANOVA on log-transformed data with Dunnett's multiple comparison test compared to baseline time, whereas patients with a S. aureus infection displayed a delayed recovery [11]. Patients with an E. coli infection had expression levels similar to those found in healthy volunteers [11]. However, the population was heterogeneous and the observed differences might therefore be explained by the large differences in disease severity between patients in the different pathogen categories [11].…”

Section: Discussionmentioning

confidence: 99%

“…Thirteen percent of the patients developed a secondary infection, which occurred after 10 [7][8][9][10][11][12][13][14][15][16][17][18][19][20] days. The sites of secondary infections are listed in Supplementary Table 3.…”

Section: Relationship Between Mhla-dr Expression and Secondary Infectmentioning

confidence: 99%

“…Multiple studies established associations between mHLA-DR expression and outcome parameters, such as secondary infections and mortality [6][7][8][9][10]. Moreover, there are indications from small studies that mHLA-DR expression differs between patients with different causative pathogens and/or sites of infection [11,12]. However, little is known about mHLA-DR expression kinetics and their relationship with sepsis characteristics and severity of disease.…”

Section: Introductionmentioning

confidence: 99%

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Monocytic HLA-DR expression kinetics in septic shock patients with different pathogens, sites of infection and adverse outcomes

et al. 2020

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Background: Decreased monocytic (m)HLA-DR expression is the most studied biomarker of sepsis-induced immunosuppression. To date, little is known about the relationship between sepsis characteristics, such as the site of infection, causative pathogen, or severity of disease, and mHLA-DR expression kinetics. Methods: We evaluated mHLA-DR expression kinetics in 241 septic shock patients with different primary sites of infection and pathogens. Furthermore, we used unsupervised clustering analysis to identify mHLA-DR trajectories and evaluated their association with outcome parameters. Results: No differences in mHLA-DR expression kinetics were found between groups of patients with different sites of infection (abdominal vs. respiratory, p = 0.13; abdominal vs. urinary tract, p = 0.53) and between pathogen categories (Gram-positive vs. Gram-negative, p = 0.54; Gram-positive vs. negative cultures, p = 0.84). The mHLA-DR expression kinetics differed between survivors and non-survivors (p < 0.001), with an increase over time in survivors only. Furthermore, we identified three mHLA-DR trajectories ('early improvers', 'delayed or non-improvers' and 'decliners'). The probability for adverse outcome (secondary infection or death) was higher in the delayed or nonimprovers and decliners vs. the early improvers (delayed or non-improvers log-rank p = 0.03, adjusted hazard ratio 2.0 [95% CI 1.0-4.0], p = 0.057 and decliners log-rank p = 0.01, adjusted hazard ratio 2.8 [95% CI 1.1-7.1], p = 0.03). Conclusion: Sites of primary infection or causative pathogens are not associated with mHLA-DR expression kinetics in septic shock patients. However, patients showing delayed or no improvement in or a declining mHLA-DR expression have a higher risk for adverse outcome compared with patients exhibiting a swift increase in mHLA-DR expression. Our study signifies that changes in mHLA-DR expression over time, and not absolute values or static measurements, are of clinical importance in septic shock patients.

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Section: Discussionsupporting

confidence: 54%

Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Section: Relationship Between Mhla-dr Expression and Secondary Infectmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Monocytic HLA-DR expression kinetics in septic shock patients with different pathogens, sites of infection and adverse outcomes

et al. 2020

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Plasma concentrations of secretory leukocyte protease inhibitor (SLPI) differ depending on etiology and severity in community-onset bloodstream infection

Lange

Cajander

Magnuson

et al. 2019

Eur J Clin Microbiol Infect Dis

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The severity of bloodstream infections (BSI) depends on pathogen, source, and host factors. Secretory leukocyte protease inhibitor (SLPI) counteracts tissue damage, balances inflammation, and is increased in pneumonia and sepsis. We aimed to evaluate whether SLPI production differs depending on etiology, disease severity, and sex in BSI and to correlate SLPI with markers of inflammation and immunosuppression. Of the adult patients with BSI, 109 were included and sampled repeatedly, from hospital admission through day 28. Controls (blood donors) were sampled twice. SLPI in plasma was measured with enzyme-linked immunosorbent assay (ELISA) technique. Streptococcus pneumoniae and Staphylococcus aureus etiology were associated with higher SLPI than Escherichia coli on days 1–2 and 3. On day 1–2, subjects with sepsis had higher SLPI concentrations than those with non-septic BSI. Pneumonia was associated with higher SLPI than a non-pulmonary source of infection. SLPI co-varied with inflammatory markers. SLPI concentrations did not differ with regard to sex in the full cohort, but men with pneumonia had higher SLPI than women on day 1–2. S. pneumoniae and S. aureus BSI were associated with higher SLPI, when compared to E. coli . Severity and pneumonia, as well as male sex in the pneumonia sub-cohort, were factors independently associated with higher SLPI. Electronic supplementary material The online version of this article (10.1007/s10096-019-03567-2) contains supplementary material, which is available to authorized users.

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Association between HLA-DR Expression and Multidrug-resistant Infection in Patients with Severe Acute Pancreatitis

Chen

Zhang

et al. 2018

CURR MED SCI

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Multidrug-resistant (MDR) bacterial infection is a common complication of severe acute pancreatitis (SAP). This study aimed to explore the association between human leukocyte antigen-antigen D-related (HLA-DR) expression and multidrug-resistant infection in patients with SAP. A total of 24 SAP patients who were admitted to Nanjing Drum Tower Hospital between May 2015 and December 2016 were enrolled in the study. The percentages of CD4+, CD8+, natural killer (NK), and HLA-DR (CD14+) cells and the CD4+/CD8+ cell ratio on days 1,7,14, and 28 after admission were determined by flow cytometry. Eighteen patients presented with the symptoms of infection. Among them, 55.6% patients (10/18) developed MDR infection. The most common causative MDR organisms were Enterobacter cloacae and Acinetobacter baumannii. The CD4+/CD8+ cell ratio and the percentage of NK cells were similar between patients with non-MDR and patients with MDR infections. In patients without infection, the HLA-DR percentage was maintained at a high level throughout the 28 days. Compared to the patients without any infection, the HLA-DR percentage in patients with non-MDR infection was reduced on day 1 but increased and reached similar levels on day 28. In patients with MDR infection, the HLA-DR percentage remained below normal levels at all-time points. It was concluded that persistent down-regulation of HLA-DR expression is associated with MDR bacterial infection in patients with SAP.

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Dynamics of monocytic HLA-DR expression differs between bacterial etiologies during the course of bloodstream infection

Cited by 22 publications

References 35 publications

Monocytic HLA-DR expression kinetics in septic shock patients with different pathogens, sites of infection and adverse outcomes

Monocytic HLA-DR expression kinetics in septic shock patients with different pathogens, sites of infection and adverse outcomes

Plasma concentrations of secretory leukocyte protease inhibitor (SLPI) differ depending on etiology and severity in community-onset bloodstream infection

Association between HLA-DR Expression and Multidrug-resistant Infection in Patients with Severe Acute Pancreatitis

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