Method for diagnosing subclinical and clinical acute rejection by analysis of predictive gene sets
Disclosed herein are methods for diagnosing acute cellular rejection (ACR) of an allograft by analysis of predictive gene sets and kits for practicing these methods.
1. A method for treating a renal allograft recipient at risk for allograft rejection, comprising the steps of:
(a) determining a renal allograft recipient is at risk for allograft rejection, by performing the steps consisting of: (i) detecting expression levels of each of the genes of a preselected gene signature set in a blood specimen obtained from the allograft recipient, and (ii) determining that there are altered expression levels of at least one gene of the preselected gene signature set, compared to reference or control levels of the same genes; and
(b) administering an anti-rejection drug or a high dose steroid to the allograft recipient determined to be at risk for allograft rejection,
wherein the gene signature set consists of the genes SPCS3, ZMAT1, ETAA1, ZNF493, CCDC82, NFYB, F13A1, TUBB1, TSC22D1, SENP6, ANXA5, EFTUD2, SENP7, AP1M1, CLK1, MAP1A and C1GALT1C1.
2. The method of claim 1 wherein the anti-rejection drug is an immunosuppressive or anti-proliferative agent.
3. The method of claim 2 wherein the immunosuppressive agent is a member selected from the group consisting of a calcineurin inhibitor (CNI), mycophenolate mofetil (MMF), sirolimus, prednisone, Mycophenolate Sodium, Azathioprine and anti-thymocyte globulin.
4. The method of claim 3 wherein the CNI is cyclosporine or tacrolimus.
5. The method of claim 1 wherein the expression levels are detected by a method selected from the group consisting of Nanostring analysis, MiSEQ analysis, RNAseq and quantitative polymerase chain reaction (qPCR) analysis.
6. The method of claim 1 wherein said allograft rejection is subclinical rejection.
7. The method of claim 1 wherein said risk of allograft rejection is expressed as acute clinical rejection.
8. A method for treating a renal allograft recipient at risk for allograft rejection, comprising the steps of:
(a) determining a renal allograft recipient is at risk for allograft rejection, by performing the steps consisting of: (i) detecting expression levels of each of the genes of a preselected gene signature set in a blood specimen obtained from the allograft recipient, and (ii) determining that there are altered expression levels of at least one gene of the preselected gene signature set, compared to reference or control levels of the same genes in a blood specimen isolated from an allograft recipient who did not suffer allograft loss; and
(b) administering an anti-rejection drug or a high dose steroid to the allograft recipient determined to be at risk for allograft rejection,
wherein the gene signature set consists of the genes SPCS3, ZMAT1, ETAA1, ZNF493, CCDC82, NFYB, F13A1, TUBB1, TSC22D1, SENP6, ANXA5, EFTUD2, SENP7, AP1M1, CLK1, MAP1A and C1GALT1C1.
9. The method of claim 8 wherein the anti-rejection drug is a member selected from the group consisting of a calcineurin inhibitor (CNI), mycophenolate mofetil (MMF), sirolimus, prednisone, Mycophenolate Sodium, Azathioprine and anti-thymocyte globulin.
10. The method of claim 9 wherein the CNI is cyclosporine or tacrolimus.
11. The method of claim 8 wherein said risk of allograft loss is expressed as subclinical rejection.
12. The method of claim 8 wherein said risk of allograft loss is expressed as acute clinical rejection.
13. A method for treating a renal allograft recipient at risk for acute cellular rejection, comprising the steps of:
(a) determining a renal allograft recipient is at risk for acute cellular rejection, by performing the steps consisting of: (i) detecting expression levels of each of the genes of a preselected gene signature set in a blood specimen obtained from the allograft recipient, and (ii) determining that there are altered expression levels of at least one gene of the preselected signature set, compared to reference or control levels of the same genes in a blood specimen isolated from an allograft recipient who did not suffer acute cellular rejection; and
(b) administering an anti-rejection drug or a high dose steroid to the allograft recipient determined to be at risk for acute cellular rejection,
wherein the gene signature set consists of the genes SPCS3, ZMAT1, ETAA1, ZNF493, CCDC82, NFYB, F13A1, TUBB1, TSC22D1, SENP6, ANXA5, EFTUD2, SENP7, AP1M1, CLK1, MAP1A and C1GALT1C1.