Peripheral blood RNA gene expression in children with pneumococcal meningitis: a prospective case–control study

Kulohoma, Benard W.; Marriage, Fiona; Vasieva, Olga; Mankhambo, Limangeni; Nguyen, Kha Minh; Molyneux, Malcolm E.; Molyneux, Elizabeth; Day, Philip J.; Carrol, Enitan D.

doi:10.1136/bmjpo-2017-000092

Cited by 20 publications

(10 citation statements)

References 38 publications

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“…Annexin 3 is found in myeloid cells in specific granules that are translocated upon cell activation (68) and interactions between the annexin family proteins and S100A proteins have previously been described (69). ANXA3 is also upregulated together with S100A9 and S100A12 in peripheral blood in children with severe infections (70). These findings suggest that interactions between annexin 3 and S100A alarmins in relation to monocyte function and immune activation warrant further investigation.…”

Section: Discussionmentioning

confidence: 78%

Expression of S100A Alarmins in Cord Blood Monocytes Is Highly Associated With Chorioamnionitis and Fetal Inflammation in Preterm Infants

et al. 2020

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Background: Preterm infants exposed to chorioamnionitis and with a fetal inflammatory response are at risk for neonatal morbidity and adverse outcome. Alarmins S100A8, S100A9, and S100A12 are expressed by myeloid cells and have been associated with inflammatory activation and monocyte modulation.Aim: To study S100A alarmin expression in cord blood monocytes from term healthy and preterm infants and relate results to clinical findings, inflammatory biomarkers and alarmin protein levels, as well as pathways identified by differentially regulated monocyte genes.Methods: Cord blood CD14+ monocytes were isolated from healthy term (n = 10) and preterm infants (<30 weeks gestational age, n = 33) by MACS technology. Monocyte RNA was sequenced and gene expression was analyzed by Principal Component Analysis and hierarchical clustering. Pathways were identified by Ingenuity Pathway Analysis. Inflammatory proteins were measured by Multiplex ELISA, and plasma S100A proteins by mass spectrometry. Histological chorioamnionitis (HCA) and fetal inflammatory response syndrome (FIRS) were diagnosed by placenta histological examination.Results: S100A8, S100A9, and S100A12 gene expression was significantly increased and with a wider range in preterm vs. term infants. High S100A8 and S100A9 gene expression (n = 17) within the preterm group was strongly associated with spontaneous onset of delivery, HCA, FIRS and elevated inflammatory proteins in cord blood, while low expression (n = 16) was associated with impaired fetal growth and physician-initiated Golubinskaya et al.Preterm Infants S100A Alarmin Expression delivery. S100A8 and S100A9 protein levels were significantly lower in preterm vs. term infants, but within the preterm group high S100A gene expression, spontaneous onset of labor, HCA and FIRS were associated with elevated protein levels. One thousand nine hundred genes were differentially expressed in preterm infants with high vs. low S100A alarmin expression. Analysis of 124 genes differentially expressed in S100A high as well as FIRS and HCA groups identified 18 common pathways and S100A alarmins represented major hubs in network analyses. Conclusion:High expression of S100A alarmins in cord blood monocytes identifies a distinct clinical risk group of preterm infants exposed to chorioamnionitis and with a fetal inflammatory response. Gene and pathway analyses suggest that high S100A alarmin expression also affects monocyte function. The connection with monocyte phenotype and inflammation-stimulated S100A expression in other cell types (e.g., neutrophils) warrants further investigation.

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Section: Discussionmentioning

confidence: 78%

Expression of S100A Alarmins in Cord Blood Monocytes Is Highly Associated With Chorioamnionitis and Fetal Inflammation in Preterm Infants

et al. 2020

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“…inflammation, immunity, blood): several recent publications have reported an increased abundance of ANXA3 transcripts in the blood of patients with colorectal cancer, pancreatic cancer, 29,30 Huntington's disease, cluster headaches, psoriasis and pneumococcal meningitis. [31][32][33][34] In the latter study, the context of which is most relevant to the topic of this review, ANXA3 was 1 of 11 markers found to be differentially expressed in the blood of children with meningitis compared with uninfected controls (the initial discovery was made in 12 subjects, and then validated using a targeted polymerase chain reaction panel in a set of 229 subjects). 31 Relatively few studies have examined a functional role for ANXA3 in immunity and inflammation.…”

Section: Additional Reference Datasets Inform On Anxa3 Restriction Anmentioning

confidence: 99%

Annexin A3 in sepsis: novel perspectives from an exploration of public transcriptome data

et al. 2020

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According to publicly available transcriptome datasets, the abundance of Annexin A3 (ANXA3) is robustly increased during the course of sepsis; however, no studies have examined the biological significance or clinical relevance of ANXA3 in this pathology. Here we explored this interpretation gap and identified possible directions for future research. Based on reference transcriptome datasets, we found that ANXA3 expression is restricted to neutrophils, is upregulated in vitro after exposure to plasma obtained from septic patients, and is associated with adverse clinical outcomes. Secondly, an increase in ANXA3 transcript abundance was also observed in vivo, in the blood of septic patients in multiple independent studies. ANXA3 is known to mediate calcium-dependent granules-phagosome fusion in support of microbicidal activity in neutrophils. More recent work has also shown that ANXA3 enhances proliferation and survival of tumour cells via a Caspase-3-dependent mechanism. And this same molecule is also known to play a critical role in regulation of apoptotic events in neutrophils. Thus, we posit that during sepsis ANXA3 might either play a beneficial role, by facilitating microbial clearance and resolution of the infection; or a detrimental role, by prolonging neutrophil survival, which is known to contribute to sepsis-mediated organ damage.

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“…It consists of a multitude of primer pairs and fluorescence-labelled probes, preloaded and dried onto a surface, that bind with high specificity to complementary sequences of nucleic acid [7]. While microarrays have been used extensively in the fields of cancer research and clinical genetics [8–13], more recently they have drawn growing attention for their potential application to infectious diseases [14–19]. While several studies have explored the comparative sensitivity and specificity of diagnostic microarrays in identifying a broad range of pathogens [20–32], the value and implications of their introduction to clinical practice remain undetermined.…”

Section: Introductionmentioning

confidence: 99%

Evaluating the use of a 22-pathogen TaqMan array card for rapid diagnosis of respiratory pathogens in intensive care

Jones

Morris

Curran

et al. 2020

Journal of Medical Microbiology

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Introduction. Pneumonia is highly prevalent in intensive care units (ICUs), with high associated mortality. Empirical treatment prioritizes breadth of coverage while awaiting laboratory diagnosis, often at the expense of antimicrobial stewardship. Microarrays use multiple parallel polymerase chain reactions to enable a rapid syndromic approach to laboratory diagnosis. Aim. To evaluate the clinical and laboratory implications of introducing a bespoke 22-pathogen TaqMan Array Card (TAC) for rapid pathogen detection in deep respiratory samples from adult ICUs. Methodology. TAC results from all ICU patients prospectively tested over a 9-month period at Cambridge’s Clinical Microbiology and Public Health Laboratory were compared to those of corresponding conventional microbiological assays (culture-, PCR- or serology-based) in terms of result agreement and time-to-result availability. Clinical impact was assessed by retrospective review of medical records. Results. Seventy-one patients were included [45 (63 %) male, median age 59). Overall result agreement was 94 %, with TAC detecting more pathogens than conventional methods. TAC detected Streptococcus pneumoniae more readily than culture (7 vs 0 cases; P=0.02). TAC did not detect Aspergillus spp. in eight culture- or galactomannan-positive cases. The median turnaround time (1 day) was significantly shorter than that of bacterial/fungal culture, Pneumocystis jirovecii PCR and galactomannan testing (each 3 days; P<0.001), atypical bacteria serology (13 days; P<0.001) and Mycobacterium tuberculosis culture (46 days; P<0.001). Earlier result availability prompted discontinuation of unnecessary antimicrobials in 15/71 (21 %) cases, but had no bearing on patient isolation/deisolation. Conclusion. TAC provided greater overall yield of pathogen detection and faster turnaround times, permitting earlier discontinuation of unnecessary antimicrobials.

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Peripheral blood RNA gene expression in children with pneumococcal meningitis: a prospective case–control study

Cited by 20 publications

References 38 publications

Expression of S100A Alarmins in Cord Blood Monocytes Is Highly Associated With Chorioamnionitis and Fetal Inflammation in Preterm Infants

Expression of S100A Alarmins in Cord Blood Monocytes Is Highly Associated With Chorioamnionitis and Fetal Inflammation in Preterm Infants

Annexin A3 in sepsis: novel perspectives from an exploration of public transcriptome data

Evaluating the use of a 22-pathogen TaqMan array card for rapid diagnosis of respiratory pathogens in intensive care

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