Dataset Information

Proteomics reveals differential diagnosis biomarkers between sepsis and hemophagocytic syndrome

ABSTRACT: Hemophagocytic Lymphohistiocytosis (HLH) shares many clinical features with sepsis. To improve HLH diagnosis and its differential diagnosis with sepsis, serum proteomic analyses of healthy donors, HLH and septic patients were performed. In this study, 24 individuals were enrolled in a label free MS/MS spectrometry analysis. Proteomic results revealed 537 differentially expressed proteins (DEP) between HLH and sepsis, 471 DEP between HLH and healthy donors and 37 DEP between sepsis and healthy donors. After protein identification and quantification, results were subjected to functional analysis to study impaired processes in each condition. These functional analyses showed that, apart from inflammation and lipid metabolism, the proteostasis network was deeply impaired in HLH condition. Considering this information, each protein fold changes, their function, and other previously published related to DEP, six proteins were validated by ELISA in a larger cohort of patients and healthy donors. Our results revealed that sCD300a, sCD300b and sCD25 could be specific serum biomarkers for HLH diagnosis. SAA-1 and LRG1 might be useful biomarkers for differential diagnosis between sepsis and HLH, and PSMB1 showed promising results for HLH specific and differential diagnosis. In this sense, PSMB1 was an interesting biomarker and its elevation in HLH patients may reflect an intensified demand for protein turnover, possibly driven by a higher activation of immunoproteasome. These insights contribute to expand our understanding of HLH pathophysiology in new pathways and highlight innovative therapeutic intervention such as Bortezomib and other next-generation inhibitors designed to modulate immunoproteasome activity

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Mikel Azkargorta

LAB HEAD: Felix Elortza

PROVIDER: PXD063444 | Pride | 2026-01-05

REPOSITORIES: Pride

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			Action	DRS
	10_210517_210331B_Susana_10_S2-B10_1_2333.d.rar	Other
	11_210517_210331B_Susana_11_S2-B11_1_2334.d.rar	Other
	11_210517_210331B_Susana_12_S2-B12_1_2335.d.rar	Other
	13_210517_210331B_Susana_13_S2-C1_1_2336.d.rar	Other
	14_210517_210331B_Susana_14_S2-C2_1_2337.d.rar	Other

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Proteomics Reveals Differential Diagnosis Biomarkers Between Sepsis and Hemophagocytic Syndrome.

Martin-Pestana David D Azkargorta Mikel M Pilar-Orive Francisco Javier FJ Redondo Silvia S Urrutia Janire J Calvo Cristina C Elortza Felix F Astigarraga Itziar I Garcia-Obregon Susana S

Biomedicines 20251217 12

<b>Background/Objectives</b>: Hemophagocytic Lymphohistiocytosis (HLH) shares many clinical features with sepsis. To improve HLH diagnosis and its differential diagnosis with sepsis, serum proteomic analyses of healthy donors, HLH and septic patients were performed. <b>Methods</b>: Twenty-four individuals were enrolled in a label-free MS/MS spectrometry analysis. STRING was conducted to study the protein-protein interactions overrepresented within the proteins of each comparison. To integrate th ...[more]

PMID: 41463121

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Project description:Expression data from CD8+ T cells and CD68+ monocytes from patients with hemophagocytic lymphohistiocytosis, sepsis, and persistent systemic inflammatory response syndrome Hemophagocytic lymphohistiocytosis (HLH) is a syndrome characterized by pathologic immune activation in which prompt recognition and initiation of immune suppression is essential for survival. Children with HLH have many overlapping clinical features with critically ill children with sepsis and persistent systemic inflammatory response syndrome (SIRS) in whom alternative therapies are indicated. To determine if plasma biomarkers could differentiate HLH from other inflammatory conditions and to better define a ‘core inflammatory signature’ of HLH, concentrations of inflammatory plasma proteins were compared in 40 patients with HLH to 47 pediatric patients with severe sepsis or SIRS. Seventeen of 135 analytes were significantly different in HLH plasma compared to SIRS/sepsis, including increased interferon-gamma (IFNg)-regulated chemokines CXCL9, CXCL10 and CXCL11. Further, a 5-analyte plasma protein classifier including these chemokines was able to differentiate HLH from SIRS/sepsis. Gene expression in CD8+ T cells and CD68+ monocytes from blood were also enriched for IFNg pathway signatures in peripheral blood cells from patients with HLH compared to SIRS/sepsis. This study identifies differential expression of inflammatory proteins as a diagnostic strategy to identify critically ill children with HLH. Further, comprehensive unbiased analysis of inflammatory plasma proteins and global gene expression demonstrates that IFNg signaling is uniquely elevated in HLH. In addition to demonstrating the ability of diagnostic criteria for HLH, sepsis and SIRS to identify groups with distinct inflammatory patterns, results from this study support the potential for prospective evaluation of inflammatory biomarkers to aid in diagnosis of and optimizing therapeutic strategies for children with distinctive hyperinflammatory syndromes.

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