Methods and compositions for evaluating graft survival in a solid organ transplant recipient

Patent metadata

Field	Value
Publication number	US-RE47057-E
Application number	US-201213529768-A
Country	US
Kind code	E1
Filing date	Jun 21, 2012
Priority date	Mar 14, 2005
Publication date	Sep 25, 2018
Grant date	Sep 25, 2018

Abstract

Methods are provided for evaluating a subject for graft survival, e.g., in terms of predicting graft survival, identifying the presence of a deleterious graft condition, such as CAN and DT, identifying the severity and class of acute rejection, etc, in a subject are provided. In practicing the subject methods, the expression of at least one gene in a sample from the subject, e.g., a blood or biopsy sample, is assayed, e.g., at the nucleic acid and/or protein level, to evaluate the subject. Also provided are compositions, systems and kits that find use in practicing the subject methods. The methods and compositions find use in a variety of applications.

First claim

What is claimed is:

1. A method of evaluating graft survival in a subject gene expression levels of at least two genes in a sample from a transplant recipient, said method comprising:
providing a sample from a transplant recipient; and
assessingmeasuring an amount of expression of at least two genes in athe sample from said subject to evaluate graft survival in said subject, wherein said at least two genes comprises HIST1H2BHIST1H2BC and IGHG3.

2. The method according to claim 1 , wherein said expression of at least two genes is assessed by assaying said sample for a nucleic acid transcript of said gene.

3. The method according to claim 1 , wherein said expression of at least two genes is assessed by assaying said sample for an expression product of said gene.

4. The method according to any of claim 1 , wherein said sample is a blood sample.

5. The method according to claim 4 , wherein said blood sample is a peripheral blood sample.

6. The method according to claim 1 , wherein said sample is a tissue biopsy sample.

7. A method according to claim 1 , wherein the method comprises: obtaining an expression profile for a sample from said subject.

8. The method according to claim 7 , wherein said expression profile is compared to a reference expression profile.

9. The method according to claim 8 7, wherein said expression profile is a nucleic acid expression profile.

10. The method according to claim 8 7, wherein said expression profile comprises expression measurements for at least 5 different genes.

11. The method according to claim 8 7, wherein said expression profile is determined using a microarray.

12. The method according to claim 11 , wherein said microarray is a genomic array.

13. A method of managing post-transplantation therapy in a subject, said method treating a transplant recipient comprising:
(a) evaluating determining that a transplant recipient has a graft survival in said subject by a method according to claim 1 ; and phenotype by evaluating results previously obtained from a quantitative determination of nucleic acid expression levels of at least two genes in a sample from the transplant recipient, and
treating said transplant recipient by maintaining a current therapeutic regimen; or

(b) determining a post-transplantation therapy protocol based on said evaluation step (a); that a transplant recipient has a graft loss phenotype by evaluating results previously obtained from a quantitative determination of nucleic acid expression levels of at least two genes in a sample from the transplant recipient, and
treating said transplant recipient by increasing or decreasing a therapeutic regimen;

wherein, said evaluating comprises comparing said results to a reference nucleic acid expression profile comprising said at least two genes; and
to manage post-transplantation therapy in said subjectwherein said at least two genes comprises HIST1H2BC and IGHG3.

14. The method according to claim 13 , wherein said subject is a human.

15. The method according to claim 1 , wherein said at least two genes further comprises one or more genes selected from: AHSA2, TNFRSF10D, MAPK9, IFNAR2, TM4SF9, MIF, SCYE1, MAPK1, TGFBR3, IGKC, IL1R2 and IGL.

16. The method of claim 7, wherein said expression profile comprises expression measurements for at least ten different genes.

17. A method of assaying gene expression in a blood sample from a graft recipient, the method comprising:
a) receiving a sample of blood from a patient that has received a graft; and b) assaying the expression of at least two genes in the blood sample, wherein said at least two genes comprises HIST1H2BC and IGHG3.

18. The method according to claim 13, wherein the therapeutic regimen is an immunosuppressive therapy.

19. The method according to claim 13, comprising: determining that the transplant recipient has a graft loss phenotype that is calcineurin-inhibitor drug nephrotoxicity (DT); and decreasing an immunosuppressive therapy.

20. The method according to claim 13, comprising: (i) determining that the transplant recipient has a graft loss phenotype that is chronic allograft nephropathy (CAN); and (ii) increasing an immunosuppressive therapy, or changing an immunosuppressive therapy by administering a different immunosuppressive drug.

21. The method according to claim 1, further comprising measuring an amount of expression of control genes in the sample.

Assignees

• Sarwal Minnie M
• Mansfield Elaine S
• Univ Leland Stanford Junior

Inventors

• Sarwal Minnie M
• Mansfield Elaine S

Classifications

• C12Q1/6883 Primary

  for diseases caused by alterations of genetic material · CPC title

• C12Q1/6876

  Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes · CPC title

• C12Q2600/118

  Prognosis of disease development · CPC title

• C12Q2600/106

  Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism · CPC title

• C12Q2600/158

  Expression markers · CPC title