Biomarker panel for diagnosis and prediction of graft rejection

Patent metadata

Field	Value
Publication number	US-9938579-B2
Application number	US-201013144047-A
Country	US
Kind code	B2
Filing date	Jan 11, 2010
Priority date	Jan 15, 2009
Publication date	Apr 10, 2018
Grant date	Apr 10, 2018

Abstract

Methods are provided for monitoring a subject having a graft for an acute rejection (AR) response, e.g., to predict, to diagnose, and/or to characterize an AR response. In practicing the subject methods, the expression level of at least one gene in a sample from the subject, e.g., a blood or biopsy sample, is evaluated, e.g., at the nucleic acid and/or protein level, to monitor the subject. Also provided are compositions, systems, kits and computer program products that find use in practicing the subject methods.

First claim

What is claimed is:

1. A system for monitoring a subject who has received an allograft for an acute rejection (AR) response, said system comprising:
(a) a gene expression evaluation element consisting of a collection of gene specific primers designed to selectively amplify genes selected from the group consisting of:
(i) CFLAR, RNF-130, IFNGR1, ITGAX, and RYBP;
(ii) NKTR, MAPK9, DUSP1, PBEF1, and PSEN1; and
(iii) NKTR, MAPK9, DUSP1, PBEF1, PSEN1, CFLAR, IFNGR1, ITGAX, RNF-130 and RYBP, wherein at least one of the gene specific primers comprises a label selected from: biotin, fluorescein, digoxigenin, an antigen, a polyvalent cation, and a chelator group.

2. The system according to claim 1 , wherein said system further comprises reagents for assaying a sample from said subject for an expression product of said genes.

3. The system according to claim 1 , wherein said collection of gene specific primers comprises primers designed to selectively amplify the genes NKTR, MAPK9, DUSP1, PBEF1, PSEN1, CFLAR, RNF-130, IFNGR1, ITGAX and RYBP and said phenotype determination element is a reference expression profile for NKTR, MAPK9, DUSP1, PBEF1, PSEN1, CFLAR, RNF-130, IFNGR1, ITGAX, and RYBP.

4. The system of claim 2 , wherein said sample is a blood sample.

5. The system of claim 1 , wherein said allograft is a heart, kidney, liver, lung, pancreas, stomach, large intestine, small intestine or bladder allograft.

6. The system according to claim 1 , wherein said collection of gene specific primers is designed to selectively amplify the genes CFLAR, RNF-130, IFNGR1, ITGAX, and RYBP.

7. The system according to claim 1 , wherein said collection of gene specific primers is designed to selectively amplify the genes NKTR, MAPK9, DUSP1, PBEF1, and PSEN1.

8. The system of claim 1 , wherein said gene specific primers are configured for use in quantitative PCR.

9. The system according to claim 1 , wherein at least one of the gene specific primers comprises a directly detectable label selected from: an isotopic moiety and a fluorescent moiety.

10. The system of claim 9 , wherein said directly detectable label is a fluorescent moiety.

11. The system according to claim 2 , wherein said additional reagents are selected from the group consisting of: dNTPs, rNTPs, one or more uniquely labeled dNTPs, one or more uniquely labeled rNTPs, gold particles, silver particles, a chemically active derivative of a fluorescent dye, an enzyme, reverse transcriptase, DNA polymerase, RNA polymerase, a hybridization buffer, a wash buffer, a spin column, signal generation and detection reagent, a streptavidin-alkaline phosphatase conjugate, a chemifluorescent substrate, a chemiluminescent substrate; and a combination thereof.

12. The system according to claim 1 , wherein the system further comprises a phenotype determination element, wherein said phenotype determination element is a database comprising a reference expression profile for said collection of gene specific primers recorded on a non-transitory computer readable medium, wherein the reference expression profile was obtained from a sample from a patient with an AR response.

Assignees

• Sarwal Minnie M
• Univ Leland Stanford Junior

Inventors

• Sarwal Minnie M

Classifications

• C12Q2600/158

  Expression markers · CPC title

• C12Q2600/118

  Prognosis of disease development · CPC title

• C12Q2600/16

  Primer sets for multiplex assays · CPC title

• C12Q1/6883 Primary

  for diseases caused by alterations of genetic material · CPC title