Proteomic biomarkers of sepsis in elderly patients

Patent metadata

Field	Value
Publication number	US-10126305-B2
Application number	US-201414392122-A
Country	US
Kind code	B2
Filing date	Jun 24, 2014
Priority date	Jun 25, 2013
Publication date	Nov 13, 2018
Grant date	Nov 13, 2018

Abstract

A proteomic expression platform to identify age-related sepsis risk is disclosed using patients with community-acquired pneumonia. A semi-quantitative plasma proteomics workflow was applied which incorporated tandem immuno affinity depletion, iTRAQ labeling, strong cation exchange fractionation, and nanoflow-liquid chromatography coupled to high resolution mass spectrometry. A protein profile was determined that exhibit statistically significant differences in expression levels amongst patients with severe sepsis as a function of age. Representative pathways that are differentially-expressed include, but are not limited to, acute phase response, coagulation signaling, atherosclerosis signaling, lipid metabolism, and production of nitric oxide/reactive oxygen species.

First claim

We claim:

1. A method for treating sepsis development, comprising:
a) providing;
i) at least one biological sample derived from an elderly patient suspected of having a community-acquired pneumonia infection;
ii) at least one peptide isolated from said at least one biological sample, wherein said at least one isolated peptide comprises at least one isobaric tag for relative and absolute quantitation (iTRAQ) reporter ion;
iii) a system comprising a liquid chromatography column and a mass spectrometer;
iv) a control proteomic pathway expression profile; and
v) a sepsis proteomic pathway expression profile;

b) contacting said at least one iTRAQ-peptide with said system to create at least one iTRAQ-peptide analysis spectrum;
c) processing said at least one iTRAQ-peptide analysis spectrum to create a patient proteomic pathway expression profile,
d) comparing said patient proteomic pathway expression profile to said control proteomic pathway expression profile and said sepsis proteomic pathway expression profile wherein at least one protein pathway of said patient proteomic pathway expression profile has an overexpression ratio when compared with said control proteomic pathway expression profile and does not have an overexpression ratio when compared with said sepsis pathway expression profile; and
d) treating said patient for sepsis development.

2. The method of claim 1 , wherein said over-expressed protein pathway is a liver retinoid X receptor activation pathway.

3. The method of claim 1 , wherein said over-expressed protein pathway is an acute phase response signaling pathway.

4. The method of claim 3 , wherein said acute phase response signaling pathway is about eight-fold over-expressed as compared to said control proteomic pathway expression profile.

5. The method of claim 1 , wherein said over-expressed protein pathway is an atherosclerosis signaling pathway.

6. The method of claim 5 , wherein said atherosclerosis signaling pathway is about seven-fold over-expressed as compared to said control proteomic pathway expression profile.

7. The method of claim 1 , wherein said over-expressed protein pathway is an interleukin-2 signaling pathway.

8. The method of claim 7 , wherein said interleukin-2 signaling pathway is about seven-fold over-expressed as compared to said control proteomic pathway expression profile.

9. The method of claim 1 , wherein said over-expressed protein pathway is a nitric oxide/oxygen reactive species pathway.

10. The method of claim 9 , wherein said nitric oxide/oxygen reactive species pathway is about seven-fold over-expressed as compared to said control proteomic pathway expression profile.

11. The method of claim 1 , wherein said over-expressed protein pathway is a clathrin-mediated endocytosis signaling pathway.

12. The method of claim 11 , wherein said clathrin-mediated endocytosis signaling pathway is about seven-fold over-expressed as compared to said control proteomic pathway expression profile.

13. The method of claim 1 , wherein said over-expressed protein pathway is an lipopolysaccharide/interleukin-1 retinoid X receptor inhibition pathway.

14. The method of claim 13 , wherein said lipopolysacharride-interleukin-1 retinoid X receptor inhibition pathway is about three-fold over-expressed as compared to said control proteomic pathway expression profile.

15. The method of claim 1 , wherein said over-expressed protein pathway is a farnesoid X receptor activation pathway.

16. The method of claim 15 , wherein said farnesoid X receptor activation pathway is about two-fold over-expressed as compared to said control proteomic pathway expression profile.

17. The method of claim 1 , wherein said over-expressed protein pathway is a hepatic stellate cell activation pathway.

18. The method of claim 17 , wherein said hepatic stellate cell activation pathway is about two-fold over-expressed as compared to said control proteomic pathway expression profile.

19. The method of claim 1 , wherein said over-expressed protein pathway is an actin cytoskeleton signaling pathway.

20. The method of claim 19 , wherein said actin cytoskeleton signaling pathway is about two-fold over-expressed as compared to said control proteomic pathway expression profile.

21. The method of claim 1 , wherein said elderly patient is of an age ranging between seventy (70 and eight-five (85) years.

22. The method of claim 2 , wherein said liver retinoid X receptor activation pathway is about ten-fold over-expressed as compared to said control proteomic pathway expression profile.

23. The method of claim 1 , wherein said treating comprises a therapy selected from the group consisting of fluid therapy, vasopressor therapy, inotropic support, antibiotics, albumin and red blood cell transfusion.

24. The method of claim 1 , wherein said treating comprises a broad spectrum antibiotic selected from the group consisting of ampicillin, amoxicillin, carbapenems, imipenem, meropenem, ertapenem, piperacillin, tazobactam, levofloxacin, gatifloxacin, moxifloxacin, ciprofloxacin, streptomycin, tetracycline, chloramphenicol and ticarcillin.

25. The method of claim 1 , wherein said treating comprises a therapy selected from the group consisting of a steroid therapy, a statin therapy, an anticoagulant therapy, a thrombomodulin therapy and an immunostimulator therapy.

Assignees

• Univ Of Pittsburgh—Of The Commonwealth System Of Higher Education
• Univ Of Pittsburg—Of The Commonwealth System Of Higher Education

Inventors

• Kellum John A
• Cao Zhiyun
• Angus Derek
• Yende Sachin Purushottam
• Robinson Rena Angilena Sowell

Classifications

• G01N33/6848 Primary

  Methods of protein analysis involving mass spectrometry · CPC title

• G01N2800/26

  Infectious diseases, e.g. generalised sepsis · CPC title