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Differential Effects of JAK1 vs. JAK2 Inhibition in Mouse Models of Hemophagocytic Lymphohistiocytosis

ABSTRACT: Differential Effects of JAK1 vs. JAK2 Inhibition in Mouse Models of Hemophagocytic Lymphohistiocytosis

PROVIDER: PRJNA962548 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR24324669.fastq.gz	Fastqsanger.gz
	SRR24324669_1.fastq.gz	Fastqsanger.gz
	SRR24324669_2.fastq.gz	Fastqsanger.gz
	SRR24324670.fastq.gz	Fastqsanger.gz
	SRR24324670_1.fastq.gz	Fastqsanger.gz

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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.

Dataset Information

Differential Effects of JAK1 vs. JAK2 Inhibition in Mouse Models of Hemophagocytic Lymphohistiocytosis

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