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Diagnostic and/or screening agents and uses therefor

A technology of selection, gene, applied in the field of diagnosis and/or screening agent and its use, which can solve the problem of inability to clear primary infection, etc.

Inactive Publication Date: 2014-03-19
IMMUNEXPRESS
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

This secondary immunosuppression is characterized by loss of delayed-type hypersensitivity to the positive control antigen, failure to clear primary infection and development of secondary infection that may include reactivation of normally latent viruses such as CMV or HHV

Method used

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  • Diagnostic and/or screening agents and uses therefor
  • Diagnostic and/or screening agents and uses therefor
  • Diagnostic and/or screening agents and uses therefor

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0236] Identification of diagnostic genes that differ between postoperative inflammation, sepsis, and inSIRS

[0237] Experimental Disease Trial Design

[0238] A clinical trial was conducted to determine whether the gene's transcript could differentiate patients with sepsis, inSIRS, and post-surgical inflammation.

[0239]Blood samples were collected at various time points to provide time course data and Affymetrix exome assay (Affymetrix HuEx-1.0) analysis of these data (see "Identification of Diagnostic Marker Genes" below) was used to analyze gene expression showing 235 specific genes Evidence of splicing changes was shown, which also differed in expression between sepsis-positive, inSIRS-positive, and post-operative patients. Of these 235 only a limited number (57) were identified that could be used as classifiers to distinguish these patient groups, the 57 genes resulting in between postoperative inflammation and inSIRS, between postoperative inflammation and sepsis, ...

Embodiment 2

[0423] Identify splice variants

[0424] For a given gene, splice variants were detected using ANOVA. The method used is similar to the Affymetrix MIDAS method. In the exon-level data, for each subject, there is the intensity of each probe set. The sample model for strength would be the population mean of genes, plus probeset effects plus subject effects plus error. where i is the probeset index and j is the subject index.

[0425] Yij=α+βi+γj+εij

[0426]This model is only applicable when there is no alternative splicing. If probeset i maps to exon e(i) and subject j is in class c(j), then alternative splicing will be represented in the model by the presence of the term δe(i)c(j). In the X:Map annotation, the probe sets matched multiple exons. This is related to the alternate exon layout in the gene, so a test for δic(j), which is the classically responsive probe set, was performed. For simplicity, the subject effect is ignored (this variation becomes part of the noise...

Embodiment 3

[0428] Gene transcripts distinguish sepsis from postoperative inflammation

[0429] Any of the gene transcripts in Table 7 are capable of distinguishing sepsis from postoperative inflammation (signs on values ​​in column logFC indicate competitive up- or down-regulation. For example, transcripts of ankddla are expected to be relative to postoperative in sepsis relative to upregulated whereas OXT1 transcripts are expected to be relatively downregulated in sepsis relative to post-surgery).

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Abstract

Disclosed are methods and apparatus for diagnosis, detection of host response, monitoring, treatment or management of sepsis, infection-negative systemic inflammatory response syndrome (SIRS) and post-surgical inflammation in mammals. More particularly, the present invention discloses marker genes and their splice variant transcripts as well as their expression products, which are useful for distinguishing between sepsis and infection-negative SIRS, including post-surgical inflammation, and to the use of these markers in grading, monitoring, treatment and management of these conditions.

Description

technical field [0001] The present invention generally relates to methods and devices for the diagnosis, host response detection, monitoring, treatment or management of sepsis, infection negative systemic inflammatory response syndrome (SIRS) and postoperative inflammation in mammals. More specifically, the present invention relates to marker genes and their splice variants and their expression products for distinguishing sepsis from infection-negative SIRS, including postoperative inflammation, and the use of these markers in the staging, monitoring, treatment and management of these conditions the use of. The present invention has practical applications for early diagnosis and diagnosis of sepsis or infection-negative SIRS or postoperative inflammation in mild or subclinical states, detection of specific cellular immune responses as part of active or progressive disease, monitoring of clinically infected subjects, And to make better treatment and management decisions for cl...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12Q1/68
CPCC12Q1/6883C12Q1/6876C12Q2600/158
Inventor 理查德·布鲁斯·布兰登默文·里斯·托马斯格伦·斯通
Owner IMMUNEXPRESS
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