ITIH4, as an inflammation biomarker, mainly increases in bacterial bloodstream infection

Ma, Yun; Li, Ruibin; Wang, Jianan; Jiang, Wencan; Yuan, Xiaozhou; Cui, Jiayue; Wang, Chengbin

doi:10.1016/j.cyto.2020.155377

Cited by 33 publications

(33 citation statements)

References 21 publications

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“…The latter two proteins showed longitudinal alterations in cluster 3, emphasizing the importance of the coagulation system in COVID-19. Interestingly, the isoform Q14626 of ITIH4, a pro-inflammatory acute phase protein that has already been implicated in bacterial infection (Ma et al ., 2021), was significantly increased in patients that did not survive (p: 2.8*10 −6 ; 2.8-fold) already at the first day of sampling, raising the possibility of prospective classification of disease mortality.…”

Section: Resultsmentioning

confidence: 99%

High-resolution longitudinal serum proteome trajectories in COVID-19 reveal patients-specific seroconversion

Geyer

Arend

Doll

et al. 2021

Preprint

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Biomarkers for COVID-19 are urgently needed. Here we bring the powerful technology of mass spectrometry (MS)-based proteomics to bear on this challenge. We measured serum proteomes of COVID-19 patients and symptomatic, but PCR-negative controls, in a time-resolved manner. In 262 controls and 458 longitudinal samples (average of 31 days) of 31 patients, hospitalized for COVID-19, a remarkable 26% of proteins changed significantly. Bioinformatics analyses revealed co-regulated groups and shared biological functions. Proteins of the innate immune system such as CRP, SAA1, CD14, LBP and LGALS3BP decreased early in the time course. In contrast, regulators of coagulation (APOH, FN1, HRG, KNG1, PLG) and lipid homeostasis (APOA1, APOC1, APOC2, APOC3, PON1) increased over the course of the disease. A global correlation map provides a systems-wide functional association between proteins, biological processes and clinical chemistry parameters. Importantly, five SARS-CoV-2 immunoassays against antibodies revealed excellent correlations with an extensive range of immunoglobulin regions, which were quantified by MS-based proteomics. The high-resolution profile of all immunoglobulin regions showed individual-specific differences and commonalities of potential pathophysiological relevance.

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Section: Resultsmentioning

confidence: 99%

High-resolution longitudinal serum proteome trajectories in COVID-19 reveal patients-specific seroconversion

Geyer

Arend

Doll

et al. 2021

Preprint

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“…Peptide peak m/z 2091.3 and 4102.3 were both identified as the fragments of SAA2, which encodes a member of the serum amyloid A family of apolipoproteins. SAA2 is a major acute phase protein and highly expressed in inflammation and tissue damage responses 43 . Derebe et al 44 and Zlatkov et al found that SAA is a retinol binding protein that transports retinol during bacterial infection.…”

Section: Discussionmentioning

confidence: 99%

Preliminary exploration on the serum biomarkers of bloodstream infection with carbapenem‐resistant Klebsiella pneumoniae based on mass spectrometry

Bao

Ding

et al. 2021

Clinical Laboratory Analysis

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Background Carbapenem‐resistant K. pneumoniae (CRKP) bloodstream infections (BSI) must be rapidly identified to improve patient survival rates. This study investigated a new mass spectrometry‐based method for improving the identification of CRKP BSI and explored potential biomarkers that could differentiate CRKP BSI from sensitive. Methods Mouse models of BSI were first established. MALDI‐TOF MS was then used to profile serum peptides in CRKP BSI versus normal samples before applying BioExplorer software to establish a diagnostic model to distinguish CRKP from normal. The diagnostic value of the model was then tested against 32 clinical CRKP BSI and 27 healthy serum samples. Finally, the identities of the polypeptides used to establish the diagnostic model were determined by secondary mass spectrometry. Results 107 peptide peaks were shared between the CRKP and normal groups, with 18 peaks found to be differentially expressed. Five highly expressed peptides in the CRKP group (m/z 1349.8, 2091.3, 2908.2, 4102.1, and 8129.5) were chosen to establish a diagnostic model. The accuracy, specificity and sensitivity of the model were determined as 79.66%, 81.48%, and 78.12%, respectively. Secondary mass spectrometry identified the Fibrinogen alpha chain (FGA), Inter‐alpha‐trypsin inhibitor heavy chain H4 (ITIH4) and Serum amyloid A‐2 protein (SAA2) as the source of the 5 serum peptides. Conclusions We successfully established a serum peptide‐based diagnostic model that distinguished clinical CRKP BSI samples from normal healthy controls. The application of MALDI‐TOF MS to measure serum peptides, therefore, represents a promising approach for early BSI diagnosis of BSI, especially for multidrug‐resistant bacteria where identification is urgent.

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“…In addition, the integrative networks identified additional putative regulators of GCase activity. The KD genes have been linked to different functions: Itih4 to inflammatory responses [ 37 ] and liver development and regeneration [ 38 ]. Hsd3b5 to steroid hormones biosynthesis [ 39 ], Ocel1 to cancer prognosis [ 40 ] and Pigt to glycosylphosphatidylinositol transfer (GPI) proteins [ 41 ].…”

Section: Discussionmentioning

confidence: 99%

Identification of genetic modifiers of murine hepatic β-glucocerebrosidase activity

Durán

Rebolledo‐Jaramillo

Olguín

et al. 2021

Biochemistry and Biophysics Reports

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The acid β-glucocerebrosidase (GCase) enzyme cleaves glucosylceramide into glucose and ceramide. Loss of function variants in the gene encoding for GCase can lead to Gaucher disease and Parkinson's disease. Therapeutic strategies aimed at increasing GCase activity by targeting a modulating factor are attractive and poorly explored. To identify genetic modifiers, we measured hepatic GCase activity in 27 inbred mouse strains. A genome-wide association study (GWAS) using GCase activity as a trait identified several candidate modifier genes, including Dmrtc2 and Arhgef1 (p=2.1x10 −7 ), and Grik5 (p=2.1x10 −7 ). Bayesian integration of the gene mapping with transcriptomics was used to build integrative networks. The analysis uncovered additional candidate GCase regulators, highlighting modules of the acute phase response (p=1.01x10 −8 ), acute inflammatory response (p=1.01x10 −8 ), fatty acid beta-oxidation (p=7.43x10 −5 ), among others. Our study revealed previously unknown candidate modulators of GCase activity, which may facilitate the design of therapies for diseases with GCase dysfunction.

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ITIH4, as an inflammation biomarker, mainly increases in bacterial bloodstream infection

Cited by 33 publications

References 21 publications

High-resolution longitudinal serum proteome trajectories in COVID-19 reveal patients-specific seroconversion

High-resolution longitudinal serum proteome trajectories in COVID-19 reveal patients-specific seroconversion

Preliminary exploration on the serum biomarkers of bloodstream infection with carbapenem‐resistant Klebsiella pneumoniae based on mass spectrometry

Identification of genetic modifiers of murine hepatic β-glucocerebrosidase activity

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