Evaluation of the S100 protein A12 as a biomarker of neonatal sepsis

Tosson, Angie M.S.; Glaser, Kirsten; Weinhage, Toni; Foell, Dirk; Aboualam, Mohamed S; Edris, Amira; Ansary, Mervat El; Lotfy, Sohilla; Speer, Christian P.

doi:10.1080/14767058.2018.1560411

Cited by 19 publications

(21 citation statements)

References 23 publications

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“…However, comparison between 4 of the 5 infants with confirmed LOS that had similar overall transcriptional responses (Fig 2) showed significantly higher levels of IL-1β compared to all infants with no LOS (median of 9.03 pg/mL in confirmed LOS versus 0.87 pg/ mL in no LOS; p<0.05). Infants with confirmed LOS also had up-regulated expression of S100A12, which encodes for the S100A12 alarmin previously implicated during neonatal and adult sepsis [41][42][43]. In line with our differential gene expression findings, the IL-1α and IL-1β levels of possible LOS infants were similar to those in infants with no LOS.…”

Section: Validation Of Transcriptional Responses In Infants With Confsupporting

confidence: 86%

Whole blood transcriptional responses of very preterm infants during late-onset sepsis

Ng¹,

Strunk²,

Lee³

et al. 2020

PLoS ONE

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Background Host immune responses during late-onset sepsis (LOS) in very preterm infants are poorly characterised due to a complex and dynamic pathophysiology and challenges in working with small available blood volumes. We present here an unbiased transcriptomic analysis of whole peripheral blood from very preterm infants at the time of LOS. Methods RNA-Seq was performed on peripheral blood samples (6-29 days postnatal age) taken at the time of suspected LOS from very preterm infants <30 weeks gestational age. Infants were classified based on blood culture positivity and elevated C-reactive protein concentrations as having confirmed LOS (n = 5), possible LOS (n = 4) or no LOS (n = 9). Bioinformatics and statistical analyses performed included pathway over-representation and proteinprotein interaction network analyses. Plasma cytokine immunoassays were performed to validate differentially expressed cytokine pathways. Results The blood leukocyte transcriptional responses of infants with confirmed LOS differed significantly from infants without LOS (1,317 differentially expressed genes). However, infants with possible LOS could not be distinguished from infants with no LOS or confirmed LOS. Transcriptional alterations associated with LOS included genes involved in pathogen recognition (mainly TLR pathways), cytokine signalling (both pro-inflammatory and inhibitory responses), immune and haematological regulation (including cell death pathways), and metabolism (altered cholesterol biosynthesis). At the transcriptional-level cytokine responses during LOS were characterised by over-representation of IFN-α/β, IFN-γ, IL-1

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Section: Validation Of Transcriptional Responses In Infants With Confsupporting

confidence: 86%

Whole blood transcriptional responses of very preterm infants during late-onset sepsis

Ng¹,

Strunk²,

Lee³

et al. 2020

PLoS ONE

View full text Add to dashboard Cite

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“…In line with our findings, a marked upregulation of S100A12 gene expression in the uterus of bitches with canine pyometra in comparison to healthy controls has been reported (31). Also, in humans, S100A12 has been proposed as a feasible biomarker of diagnostic and prognostic in sepsis, showing higher plasma concentration in patients with deadly septic shock in comparison to healthy individuals and survivor patients (32), and showed high sensitivity and specificity as serum biomarker of neonatal sepsis (33). Vimentin is a type of intermediate filament protein that is up-regulated during epithelial-to-mesenchymal transition, a process that occurs during neural development, wound healing, and cancer metastasis (34).…”

Section: Discussionmentioning

confidence: 99%

Changes in the Salivary Proteome Associated With Canine Pyometra

et al. 2020

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The present study evaluated for the first time changes in the saliva proteome in bitches with pyometra through a high-throughput quantitative proteomic analysis. The aims were to explore whether saliva composition could reflect the physiopathological changes occurring in canine pyometra and to identify potential biomarkers of the disease. Saliva samples from six healthy (H) and six bitches with pyometra (P) were analyzed using tandem mass tags-based approach. Additionally, 15 samples were used for the validation of changes in haptoglobin (Hp) concentration in saliva of dogs with pyometra. Proteomic analysis quantified 707 proteins in saliva. Comparison of the two groups revealed 16 unique proteins significantly modulated in saliva, with S100A calcium-binding protein 12 (S100A12), vimentin, and Hp the most up-regulated in canine pyometra. According to PANTHER (Protein Analysis Through Evolutionary Relationships) classification tool, these proteins are mainly related to proinflammatory mediators, acute-phase proteins, and sepsis. In conclusion, it can be stated that there are changes in various proteins in saliva in canine pyometra reflecting different physiopathological changes occurring in this disease. These proteins could be a source of potential non-invasive biomarkers for this disease that should be confirmed in future studies.

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“…Published concentrations of TNF-α, IL-1β, IL-17AF and IL-8 in infants with sepsis are inconsistent, with some studies reporting results similar to ours, [10-12, 15, 17] and others reporting higher cytokine concentrations in septic infants. [14][15][16][17] The reasons underlying these discrepant results are unclear. Several factors may affect cytokine concentrations, including GA, [10] EOS vs LOS (which generally have different aetiologies), [12] sepsis definition (culture proven vs clinical sepsis) [15] and inclusion of Gram-negative, fungal and NEC-related infections (which may elicit different cytokine responses).…”

Section: Elevated Circulating Cytokine Concentrations Are Associated mentioning

confidence: 99%

“…[8] It is unclear whether the immediate response of preterm infants with LOS is hyper-or hypoinflammatory. [9] Cytokine concentrations at the time of neonatal sepsis are inconsistent, partly as studies often include both LOS and early-onset sepsis (EOS; occurring <72 hours after birth), [10][11][12] and a wide range of GA, [11,[13][14][15][16][17][18] making interpretation of cytokine responses challenging. We therefore aimed to characterise key cytokines [5] in plasma at the time of evaluation for suspected LOS in a homogeneous cohort of very preterm infants (born <30 weeks GA) enrolled in an observational cohort study of innate immune ontogeny.…”

Section: Introductionmentioning

confidence: 99%

Plasma cytokine profiles in very preterm infants with late-onset sepsis

et al. 2020

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Introduction Deficiencies in innate immune responses may contribute to the increased susceptibility to infection in preterm infants. In vivo cytokine profiles in response to sepsis in very preterm infants are not fully understood. Aims To characterise plasma pro-and anti-inflammatory cytokine concentrations and pre-defined ratios in very preterm infants with late-onset sepsis (LOS). Methods In this observational study, peripheral blood samples were collected at the time of evaluation for suspected LOS from 31 preterm infants (<30 weeks gestational age). Plasma cytokine concentrations were determined by 12-plex immunoassay. Results IL-10, IFN-γ, IL-12p70, IP-10, IL-6 and CCL2 were elevated in the majority infants with LOS (n = 12) compared to those without LOS (n = 19). There was no difference in TNF-α, IL-1β, IL-17AF, IL-8 and IL-15 concentrations between groups. IL-10/TNF-α ratios were increased, while CCL2/IL-10 and IL-12p70/IL-10 ratios were decreased in infants with LOS compared to those without. Conclusion Very preterm infants have a marked innate inflammatory response at the time of LOS. The increase in IL-10/TNF-α ratio may indicate early immune hypo-responsiveness. Longitudinal studies with a larger number of participants are required to understand immune responses and clinical outcomes following LOS in preterm infants.

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Evaluation of the S100 protein A12 as a biomarker of neonatal sepsis

Cited by 19 publications

References 23 publications

Whole blood transcriptional responses of very preterm infants during late-onset sepsis

Whole blood transcriptional responses of very preterm infants during late-onset sepsis

Changes in the Salivary Proteome Associated With Canine Pyometra

Plasma cytokine profiles in very preterm infants with late-onset sepsis

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