METHODS AND ASSAYS RELATING TO THE TREATMENT OF INFECTION

• US 20200131578A1
• Filed: 12/17/2019
• Published: 04/30/2020
• Est. Priority Date: 11/13/2013
• Status: Active Application

• Current Assignee: The General Hospital Corporation (Mass General Brigham, Inc.)
• Original Assignee: The General Hospital Corporation (Mass General Brigham, Inc.)
• Inventors: RAHME, Laurence, YAN, Shuangchun, QUE, Yok-Ai, TSURUMI, Amy
• Application Number:
  US16/716,613
• Publication Number:
  US 20200131578A1
• Time in Patent Office: Days
• CPC Class Codes: C12Q 1/6883 for diseases caused by alterations of genetic material
• CPC Class Codes: C12Q 2600/106 Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism
• CPC Class Codes: C12Q 2600/156 Polymorphic or mutational markers
• CPC Class Codes: C12Q 2600/158 Expression markers
• CPC Class Codes: G01N 2800/26 Infectious diseases, e.g. generalised sepsis
• CPC Class Codes: G01N 2800/52 Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
• CPC Class Codes: G01N 33/6893 related to diseases not provided for elsewhere

Abstract

The technology described herein is directed to the diagnosis, prognosis, and treatment of infection, e.g. after burn injury.

Claims

1. A method comprising:

(a) obtaining a leukocyte sample from a burn patient 16 years of age or older and suspected of being at risk of a Pseudomonas or Staphylococci infection or having a Pseudomonas or Staphylococci infection;

(b) isolating RNA from the sample;

(c) analyzing the isolated RNA using RT-PCR for gene expression levels of at least one gene selected from the group of;

Thrombospondin 1 (THBS1);

cyclin D2 (CCND2);

MyoD family inhibitor domain containing (MDFIC);

SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 4 (SMARCA4);

nuclear receptor binding SET domain protein 3 (WHSC1L1);

transmembrane protein 50B (TMEM50B);

DDB1 and CUL4 associated factor 7 (DCAF7); and

oxysterol binding protein like 8 (OSBPL8);

(d) determining the values of total body surface area (TBSA) burns, age, and inhalation status of the burn patient; and

(e) multiplying the TBSA value by 0.0423;

multiplying the age value by 0.0652;

multiplying the inhalation status value by 3.5132; and

multiplying the expression level of each measured gene by a coefficient selected from the group of;

0.8321 for the expression level of Thrombospondin 1 (THBS1) analyzed using sequence comprising probe 201108;

0.8448 for the expression level of Thrombospondin 1 (THBS1) analyzed using the sequence comprising probe 201109, 0.0714 for the expression level of Thrombospondin 1 (THBS1) analyzed using the sequence comprising probe 201110;

0.033 for the expression level of cyclin D2 (CCND2);

−

0.146 for the expression level of MyoD family inhibitor domain containing (MDFIC);

−

1.0108 for the expression level of SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 4 (SMARCA4);

−

1.2438 for the expression level of nuclear receptor binding SET domain protein 3 (WHSC1L1);

−

0.167 for the expression level of transmembrane protein 50B (TMEM50B);

−

1.4905 for the expression level of DDB1 and CUL4 associated factor 7 (DCAF7);

0.1821 for the expression level of oxysterol binding protein like 8 (OSBPL8); and

adding the resulting products to yield a risk value.

2. The method of claim 1, wherein a risk value is greater than or about −

1.1912 indicates the subject should be administered at least one treatment selected from the group consisting of;

antibiotics;

immunotherapy; and

LPS removal.

3. The method of claim 1, wherein the sample comprises blood or plasma.