Method and kits for prediction of acute rejection and renal allograft loss using pre-transplant transcriptomic signatures in recipient blood
AssigneeIcahn School of Medicine at Mount Sinai
InventorsBarbara Murphy, Weijia Zhang
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Abstract
Disclosed herein are gene signature sets expressed by kidney allograft recipients prior to transplant that determine the risk for acute rejection (AR) post-transplant and methods of using the gene signature sets for identifying renal allograft recipients at risk for acute rejection. Also disclosed herein are kits for use in the invention which comprise primer pairs for the gene signature sets.
Claims19
A method for identifying a renal allograft candidate at risk of developing acute rejection comprising the steps of
- (a) determining the expression levels of a gene signature set in a pre-transplant blood specimen from the renal allograft candidate, said gene signature set including GZMH, ADGRG1, S1PR5, FGFBP2, NKG7, PRF1, KIAA1671, LAG3, TARP, FCRL6, FASLG, TBX21, TOX, ZNF831, CD8A, C1orf21, CCR5, LDOC1L, CCDC102A, HOPX, PRKCH, SLC25A34 and F12;
- (b) comparing the expression levels of the gene signature set with the expression levels of a gene signature set in a control,
- (c) identifying the renal allograft candidate as being at risk for allograft rejection if the expression level of one or more genes in the gene signature set in the specimen differs from the expression level of the same one or more genes in the gene signature set in the control, and
- (d) treating the renal allograft candidate identified as being at risk for acute rejection or allograft loss with induction therapy.
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A method for identifying a candidate for a renal allograft transplant at risk of acute rejection of the allograft before transplantation comprising the steps of
- (a) obtaining a blood specimen from the renal allograft candidate;
- (b) isolating mRNA from the blood specimen;
- (c) synthesizing cDNA from the mRNA;
- (d) determining the expression levels of a gene signature set in said renal allograft candidate's blood, said gene signature set including GZMH, ADGRG1, S1PR5, FGFBP2, NKG7, PRF1, KIAA1671, LAG3, TARP, FCRL6, FASLG, TBX21, TOX, ZNF831, CD8A, C1orf21, CCR5, LDOC1L, CCDC102A, HOPX, PRKCH, SLC25A34 and F12;
- (e) identifying the renal allograft candidate as being at risk for acute rejection and allograft loss if the expression level of one or more genes in the gene signature set in the renal allograft candidate's blood specimen differs compared to the expression level of the same one or more genes in the control blood specimen, and
- (f) treating the renal allograft candidate identified as being at risk for acute rejection or allograft loss with induction therapy.
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A kit for identifying renal allograft candidates at risk for acute rejection and allograft loss comprising in one or more separate containers primer pairs for the gene signature set:
- GZMH, ADGRG1, S1PR5, FGFBP2, NKG7, PRF1, KIAA1671, LAG3, TARP, FCRL6, FASLG, TBX21, TOX, ZNF831, CD8A, C1orf21, CCR5, LDOC1L, CCDC102A, HOPX, PRKCH, SLC25A34, F12, and buffers, positive and negative controls and instructions for use.
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A method for selecting a renal allograft candidate for induction therapy before transplantation to reduce the risk of renal acute rejection or allograft loss which comprises
- comparing the expression level of a gene signature set obtained from the renal allograft candidate with the expression level of a gene signature set in a control sample obtained from a renal allograft recipient that did not suffer acute renal rejection, and selecting the renal allograft candidate for treatment with induction therapy if the expression level of one or more genes in the gene signature set from the renal allograft candidate differs compared to the expression level of the same one or more of the genes in the gene signature set in the control, said gene signature set including GZMH, ADGRG1, S1PR5, FGFBP2, NKG7, PRF1, KIAA1671, LAG3, TARP, FCRL6, FASLG, TBX21, TOX, ZNF831, CD8A, C1orf21, CCR5, LDOC1L, CCDC102A, HOPX, PRKCH, SLC25A34 and F12, and
- administering induction therapy to said renal allograft candidate.
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Dependencies are inferred from the claim text.