Evidence map›Paper›PMID 40885913›Full record

ArticleClinical proteomics2025

Plasma proteomics in septic shock and alcohol-related pancreatitis: a hyaluronan-centered approach.

Jaap van der Heijden, Asanda Mazubane, Marko Sallisalmi, Egor Vorontsov, Jyrki Tenhunen, Annelie Barrueta Tenhunen

Abstract read
In one paragraph

Article in Clinical proteomics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
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1 · What the graph read from it

What it found

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2 · The registry

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3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

6 authors.

Jaap van der HeijdenDepartment of Surgical Sciences, Anesthesiology and Intensive Care, Uppsala University, 75185, Uppsala, Sweden. jaap.vanderheijden@surgsci.uu.se.
Asanda MazubaneDepartment of Surgical Sciences, Anesthesiology and Intensive Care, Uppsala University, 75185, Uppsala, Sweden.
Marko SallisalmiDivision of Anaesthesia and Intensive Care Medicine, Intensive Care Units, Department of Surgery, Helsinki University Hospital, 260, Helsinki, Finland.
Egor VorontsovProteomics Core Facility, Sahlgrenska Academy, University of Gothenburg, 41390, Gothenburg, Sweden.
Jyrki TenhunenDepartment of Surgical Sciences, Anesthesiology and Intensive Care, Uppsala University, 75185, Uppsala, Sweden.
Annelie Barrueta TenhunenDepartment of Surgical Sciences, Anesthesiology and Intensive Care, Uppsala University, 75185, Uppsala, Sweden.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundSepsis is a critical condition characterized by a dysregulated immune response to infection. As sepsis develops to septic shock, its most severe form, morbidity and mortality increases. Hyaluronan is a key component of the extracellular matrix and the endothelial glycocalyx. In sepsis, plasma hyaluronan concentrations are increased and correlate with disease severity. In this study we aimed to explore and compare the proteomic profiles of hyaluronan-associated proteins in patients with the dysregulated immune response of septic shock and the sterile inflammation of acute alcohol-related pancreatitis.

methodsThe present study involved proteomic analysis of patients with septic shock (n = 13), pancreatitis (n = 8), and healthy controls (n = 8). LC-MS/MS was conducted for peptide analysis. Hyaluronan-associated proteins were identified using the UniProt REST API, followed by functional and pathway enrichment analyses with GOATOOLS and GSEApy. Statistical analyses, including ANOVA and post hoc tests, were performed using Python and SPSS, with significance set at p < 0.05.

resultsFrom a total sum of 663 detected unique plasma proteins, 15 were identified as hyaluronan-related proteins. Plasma levels of 11/15 proteins separated septic shock from pancreatitis in a statistically significant manner. Between the groups differences were apparent on day 1 (8 proteins in septic shock versus 3 in pancreatitis) and day 4 (6 proteins in septic shock versus 3 in pancreatitis) relative to controls. Functional enrichment analysis revealed associations with extracellular matrix organization, proteolytic enzyme regulation, and hyaluronan metabolism. Notably, members of the inter-alpha-inhibitor family demonstrated distinct patterns, with ITIH3 levels increasing and ITIH1, ITIH2, and ITIH4 levels decreasing in septic shock compared to controls. Additionally, plasma hyaluronidase inhibition correlated positively with ITIH3 levels.

conclusionThe present study explored the role of hyaluronan-related proteins in septic shock pathophysiology, revealing potential dysregulation associated with sepsis severity. The decrease in ITIH1, ITIH2 and ITIH4, as compared to the increase in ITIH3, suggest a complex alteration in the protein balance of the IαI-family in sepsis. Overall, the altered proteomic profile of hyaluronan-related proteins as reflected by the GO terms indicates a complex dysregulation not only in hyaluronan metabolism and extracellular matrix, but also in the regulation of several proteolytic enzymes. Future studies on this area are warranted.

Indexed as

Extracellular matrixGlycocalyxHyaluronanHyaluronidaseHyaluronidase inhibitionInter-alpha-trypsin inhibitorPancreatitisProteomicsSepsis

Identifiers

PMID40885913
PMCPMC12398169

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.