Method for identifying kidney allograft recipients at risk for chronic injury
A method for identifying a renal allograft recipient at risk for chronic allograft damage or interstutial fibrosis and tubular atrophy (IF/TA) by comparing the transcription level of a preselected gene signature set with the transcription level of a comparison standard, and diagnosing the recipient as being at risk for chronic allograft damage if the transcription level of the preselected gene signature set is significantly higher than the transcription level of the comparison standard.
1. A method for treating a human renal allograft recipient at risk for chronic allograft damage or interstitial fibrosis and tubular atrophy (IF/TA) comprising the steps of:
(a) selecting a human renal allograft recipient identified as being at risk for chronic allograft damage or IF/TA based on detected transcription levels of a preselected gene signature set which are significantly higher than the transcription levels of a comparison standard expression library obtained from a renal allograft biopsy specimen of a subject that did not develop chronic allograft damage or IF/TA, said transcription levels obtained by
i. synthesizing cDNA from mRNA isolated from a biopsy specimen obtained from said renal allograft recipient, and
ii. detecting the transcription levels of the preselected gene signature set in the cDNA, wherein said gene signature set comprises the genes KLHL13, KAAG1, MET, SPRY4, SERINC5, CHCHD10, FJX1, WNT9A, RNF149, ST5, TGIF1, RXRA and ASB15; and
(b) administering to the human renal allograft recipient in which the detected transcription levels of the preselected gene signature set are significantly higher than the transcription levels of the comparison standard expression library an effective amount of an anti-fibrotic agent, an immunosuppressive agent, or both.
2. The method of claim 1 which comprises detecting the transcription levels of said preselected gene signature set of step (a) with RT-PCR analysis.
3. The method of claim 1 which comprises detecting the transcription levels of said preselected gene signature set of step (a) with Nanostring analysis.
4. The method of claim 1 which comprises detecting the transcription levels of said preselected gene signature set of step (a) with RNA SEQ analysis.
5. The method of claim 1 wherein said anti-fibrotic agent is selected from the group consisting of Pirfenidone, relaxin, Bone morphogenetic protein 7 (BMP-7) and Hepatic growth factor (HGF).
6. The method of claim 1 wherein said immunosuppressive agent is selected from the group consisting of a calcineurin inhibitor (CNI), prednisone, mycophenolate mofeti, belatacept, Mycophenolate Sodium and Azathioprine.
7. The method of claim 6 wherein the CNI is cyclosporine or tacrolimus.
8. The method of claim 1 wherein the comparison standard expression library comprises a blood specimen from an allograft recipient that did not suffer from chronic allograft damage or IF/TA.
9. The method of claim 1 wherein said renal allograft recipient is suffering from allograft rejection.
10. The method of claim 9 wherein said allograft rejection is acute cellular rejection.
11. The method of claim 9 wherein said allograft rejection is subcellular rejection.
12. The method of claim 1 which comprises detecting the transcription levels of said preselected gene signature set of step (a) with MiSeq analysis.