“…Both IL7R3 and IL7R7 transcripts expressions were decreased in septic shock patients’ T cells (Fig. 2), as we previously observed in whole blood [8]. While whole blood IL7R3 and IL7R7 expressions may be impacted by sepsis-induced lymphopenia, these transcripts are also intrinsically regulated in T cells.Fig.…”
supporting
confidence: 75%
“…Several transcripts missing the exon 6, coding for the transmembrane domain have been identified, such as IL7R3 [4, 6] and IL7R7 (Ensembl). We recently showed that plasmatic sCD127 concentration and whole blood IL7R3 transcript expression were decreased in septic shock [7, 8]. However, sCD127 protein and transcripts regulations in survivor and non-survivor patients differed, with higher sCD127 concentration and lower IL7R3 expression in non-survivors.…”
“…Both IL7R3 and IL7R7 transcripts expressions were decreased in septic shock patients’ T cells (Fig. 2), as we previously observed in whole blood [8]. While whole blood IL7R3 and IL7R7 expressions may be impacted by sepsis-induced lymphopenia, these transcripts are also intrinsically regulated in T cells.Fig.…”
supporting
confidence: 75%
“…Several transcripts missing the exon 6, coding for the transmembrane domain have been identified, such as IL7R3 [4, 6] and IL7R7 (Ensembl). We recently showed that plasmatic sCD127 concentration and whole blood IL7R3 transcript expression were decreased in septic shock [7, 8]. However, sCD127 protein and transcripts regulations in survivor and non-survivor patients differed, with higher sCD127 concentration and lower IL7R3 expression in non-survivors.…”
“…This could account for an unequal distribution in the initial infectious site as it is reported that the expression of these genes is impacted by the site of the initial infection in sepsis 47 . In accordance, the identified "severe" cluster gathers the expression of genes associated with poor outcome and high mortality described in previous studies 30,[46][47][48] . Interestingly, the SEB-based IFA also identified S3 and SV3 clusters of septic patients who seem to display an intermediate-to-severe phenotype.…”
Section: Discussionsupporting
confidence: 88%
“…The clusters S2 and SV2, that could be considered as the “severe” clusters, included all the non-survivors at day 28 who did not develop any HAI before death (n = 4 in the discovery cohort and n = 3 in the validation cohort). Of note, genes previously described in subgroups of septic patients as being associated with mortality were, herein, found to be modulated specifically in the “severe” cluster in the discovery ( DIRK2 , ADGRE3 , CCNB1IP1 30 , and IL7R/CD127 46 ) and validation ( MDC1 30 and IFI44L 47 ) cohorts. This could account for an unequal distribution in the initial infectious site as it is reported that the expression of these genes is impacted by the site of the initial infection in sepsis 47 .…”
The complexity of sepsis pathophysiology hinders patient management and therapeutic decisions. In this proof-of-concept study we characterised the underlying host immune response alterations using a standardised immune functional assay (IFA) in order to stratify a sepsis population. In septic shock patients, ex vivo LPS and SEB stimulations modulated, respectively, 5.3% (1/19) and 57.1% (12/21) of the pathways modulated in healthy volunteers (HV), highlighting deeper alterations induced by LPS than by SEB. SEB-based clustering, identified 3 severity-based groups of septic patients significantly different regarding mHLA-DR expression and TNFα level post-LPS, as well as 28-day mortality, and nosocomial infections. Combining the results from two independent cohorts gathering 20 HV and 60 patients, 1 cluster grouped all HV with 12% of patients. The second cluster grouped 42% of patients and contained all non-survivors. The third cluster grouped 46% of patients, including 78% of those with nosocomial infections. The molecular features of these clusters indicated a distinctive contribution of previously described genes defining a “healthy-immune response” and a “sepsis-related host response”. The third cluster was characterised by potential immune recovery that underlines the possible added value of SEB-based IFA to capture the sepsis immune response and contribute to personalised management.
“…Quantification of the IL-7 receptor gene expression in the blood helps to identify patients with sepsis at risk of death. 107 The neutrophil transcriptome is a promising new source of biomarkers in sepsis with lipocalin-2 (also known as gelatinase-associated lipocalin) and matrix metallopeptidase 8 among the most promising ones. 108,109 Transcriptomics could identify endotypes of sepsis with distinct clinical and biological features and differential treatment responses.…”
Section: Lack Of Standardisation Of Immunological Test For Clinical Amentioning
Increasing evidence supports a central role of the immune system in sepsis, but the current view of how sepsis affects immunity, and vice versa, is still rudimentary. The European Group on Immunology of Sepsis has identified major gaps that should be addressed with high priority, such as understanding how immunological alterations predispose to sepsis, key aspects of the immunopathological events during sepsis, and the long-term consequences of sepsis on patient's immunity. We discuss major unmet topics in those three categories, including the role of key immune cells, the cause of lymphopenia, organ-specific immunology, the dynamics of sepsis-associated immunological alterations, the role of the microbiome, the standardisation of immunological tests, the development of better animal models, and the opportunities offered by immunotherapy. Addressing these gaps should help us to better understand sepsis physiopathology, offering translational opportunities to improve its prevention, diagnosis, and care.
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