Methods for Diagnosis of Sepsis

• US 20200131577A1
• Filed: 11/20/2019
• Published: 04/30/2020
• Est. Priority Date: 03/12/2015
• Status: Active Application

• Current Assignee: Board of Trustees of the Leland Stanford Junior University (Stanford Management Co.)
• Original Assignee: Board of Trustees of the Leland Stanford Junior University (Stanford Management Co.)
• Inventors: Khatri, Purvesh, Sweeney, Timothy E.
• Application Number:
  US16/689,926
• Publication Number:
  US 20200131577A1
• 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 2600/158 Expression markers
• CPC Class Codes: G16B 25/00 ICT specially adapted for hybridisation; ICT specially adapted for gene or protein expression
• CPC Class Codes: G16B 25/10 Gene or protein expression profiling; Expression-ratio estimation or normalisation
• CPC Class Codes: G16B 25/20 Polymerase chain reaction [PCR]; Primer or probe design; Probe optimisation
• CPC Class Codes: G16H 50/20 for computer-aided diagnosis, e.g. based on medical expert systems
• CPC Class Codes: Y02A 90/10 Information and communication technologies [ICT] supporting adaptation to climate change, e.g. for weather forecasting or climate simulation

Abstract

Methods for diagnosis of sepsis are disclosed. In particular, the invention relates to the use of biomarkers for aiding diagnosis, prognosis, and treatment of sepsis, and to a panel of biomarkers that can be used to distinguish sepsis from noninfectious sources of inflammation, such as caused by traumatic injury, surgery, autoimmune disease, thrombosis, or systemic inflammatory response syndrome (SIRS).

Claims

1-26. -26. (canceled)

27. A kit comprising agents for the diagnosis of sepsis, wherein the kit comprises oligonucleotides that specifically hybridize to RNA transcripts of up to 30 genes, wherein the up to 30 genes include two or more of ADAMTS3, ANKRD22, ANXA3, AP3B2, ARL8A, B3GNT8, BATF, BPI, BST1, C1orf162, C3AR1, C9orf103, C9orf95, CCR1, CD177, CD63, CD82, CEACAM1, CLEC5A, DHRS9, EMR1, FAM89A, FCER1G, FCGR1B, FES, FFAR3, FIG4, GNA15, GPR84, HK3, HP, IL10, IL18R1, KCNE1, LCN2, LIN7A, OSCAR, OSTalpha, P2RX1, PADI2, PECR, PLAC8, PLB1, PNPLA1, PPM1M, PSTPIP2, RETN, RGL4, S100A12, SEPHS2, SETD8, SGSH, SIGLEC9, SLC26A8, SPPL2A, SQRDL, TCN1, ZDHHC19, ZDHHC3, ARHGEF18, CACNA2D3, CNNM3, GLO1, GRAMD1C, HACL1, HLA-DPB1, KIAA1370, KLHDC2, METAP1, MRPS35, MTCH1, NOC3L, ODC1, PRKRIR, RPGRIP1, RPUSD4, SETD1B, TBC1D4, TGFBI, TOMM20, UBE2Q2, and WDR75.

28. The kit of claim 27, wherein the kit comprises oligonucleotides that specifically hybridize to RNA transcripts of up to 30 genes, wherein the up to 30 genes include three or more of ADAMTS3, ANKRD22, ANXA3, AP3B2, ARL8A, B3GNT8, BATF, BPI, BST1, C1orf162, C3AR1, C9orf103, C9orf95, CCR1, CD177, CD63, CD82, CEACAM1, CLEC5A, DHRS9, EMR1, FAM89A, FCER1G, FCGR1B, FES, FFAR3, FIG4, GNA15, GPR84, HK3, HP, IL10, IL18R1, KCNE1, LCN2, LIN7A, OSCAR, OSTalpha, P2RX1, PADI2, PECR, PLAC8, PLB1, PNPLA1, PPM1M, PSTPIP2, RETN, RGL4, S100A12, SEPHS2, SETD8, SGSH, SIGLEC9, SLC26A8, SPPL2A, SQRDL, TCN1, ZDHHC19, ZDHHC3, ARHGEF18, CACNA2D3, CNNM3, GLO1, GRAMD1C, HACL1, HLA-DPB1, KIAA1370, KLHDC2, METAP1, MRPS35, MTCH1, NOC3L, ODC1, PRKRIR, RPGRIP1, RPUSD4, SETD1B, TBC1D4, TGFBI, TOMM20, UBE2Q2, and WDR75.

29. The kit of claim 27, wherein the kit comprises oligonucleotides that specifically hybridize to RNA transcripts of up to 30 genes, wherein the up to 30 genes include two or more of CEACAM1, ZDHHC19, C9orf95, GNA15, BATF, C3AR1, KIAA1370, TGFBI, MTCH1, RPGRIP1, and HLA-DPB1.

30. The kit of claim 27, wherein the kit comprises oligonucleotides that specifically hybridize to RNA transcripts of up to 30 genes, wherein the up to 30 genes include three or more of CEACAM1, ZDHHC19, C9orf95, GNA15, BATF, C3AR1, KIAA1370, TGFBI, MTCH1, RPGRIP1, and HLA-DPB1.

31. A method for analyzing a sample, comprising:

(a) obtaining a biological sample from a patient; and

(b) detecting the levels of expression of two or more biomarkers selected from ADAMTS3, ANKRD22, ANXA3, AP3B2, ARL8A, B3GNT8, BATF, BPI, BST1, C1orf162, C3AR1, C9orf103, C9orf95, CCR1, CD177, CD63, CD82, CEACAM1, CLEC5A, DHRS9, EMR1, FAM89A, FCER1G, FCGR1B, FES, FFAR3, FIG4, GNA15, GPR84, HK3, HP, IL10, IL18R1, KCNE1, LCN2, LIN7A, OSCAR, OSTalpha, P2RX1, PADI2, PECR, PLAC8, PLB1, PNPLA1, PPM1M, PSTPIP2, RETN, RGL4, S100A12, SEPHS2, SETD8, SGSH, SIGLEC9, SLC26A8, SPPL2A, SQRDL, TCN1, ZDHHC19, ZDHHC3, ARHGEF18, CACNA2D3, CNNM3, GLO1, GRAMD1C, HACL1, HLA-DPB1, KIAA1370, KLHDC2, METAP1, MRPS35, MTCH1, NOC3L, ODC1, PRKRIR, RPGRIP1, RPUSD4, SETD1B, TBC1D4, TGFBI, TOMM20, UBE2Q2, and WDR75 in the biological sample.

32. The method of claim 31, wherein the method comprises detecting the levels of expression of three or more of the biomarkers.

33. The method of claim 31, wherein the method comprises detecting the levels of expression of two or more of biomarkers selected from CEACAM1, ZDHHC19, C9orf95, GNA15, BATF, C3AR1, KIAA1370, TGFBI, MTCH1, RPGRIP1, and HLA-DPB1 in the biological sample.

34. The method of claim 31, wherein the method comprises detecting the levels of expression of three or more of the biomarkers selected from CEACAM1, ZDHHC19, C9orf95, GNA15, BATF, C3AR1, KIAA1370, TGFBI, MTCH1, RPGRIP1, and HLA-DPB1 in the biological sample.

35. The method of claim 34, wherein the method comprises detecting the levels of expression of all of the biomarkers.

36. The method of claim 31, wherein the method comprises identifying the human subject as having sepsis based on the expression of the biomarkers.

37. The method of claim 36, further comprising administering an antibiotic to the subject.

38. The method of claim 37, wherein the antibiotic is a broad-spectrum antibiotic.

39. The method of claim 31, wherein the levels of expression of the biomarkers are measured by microarray analysis, polymerase chain reaction (PCR), reverse transcriptase polymerase chain reaction (RT-PCR), isothermal amplification, a Northern blot, or a serial analysis of gene expression (SAGE).

40. The method of claim 31, wherein the biological sample comprises blood, buffy coat, band cells, or metamyelocytes.

41. The method of claim 31, wherein the biomarkers are RNA biomarkers.