Methods and compositions for assessing acute rejection
AssigneeNovartis AG
InventorsFriedrich Raulf, Pierre Saint-Mezard, Hai Zhang
Life of this patent
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Abstract
The invention relates to the analysis and identification of genes that are up-regulated simultaneously in transplant rejection. This simultaneous up-regulation of genes provides a molecular signature to accurately detect transplant rejection.
Claims47
A method for assessing the onset of rejection of a transplanted organ in a subject, comprising:
- obtaining a post-transplantation sample from the subject;
- determining the level of gene expression in the post-transplantation sample of combination of a plurality of genes in Table 3, wherein at least one gene is associated with the NADPH oxidase pathway;
- comparing the magnitude of gene expression of the at least one gene in the post-transplantation sample with the magnitude of gene expression of the same gene in a control sample;
- and
- determining whether at least one gene is up-regulated relative to the control sample, wherein up-regulation of at least one gene indicates that the subject is likely to experience transplant rejection, thereby assessing the onset of rejection of the transplanted organ in the subject.
A method for assessing the onset of rejection of a transplanted organ in a subject, comprising:
- obtaining a post-transplantation sample from the subject;
- determining the magnitude of gene expression in the post-transplantation sample of a combination of a plurality of genes selected from the group consisting of a gene associated with hematopoiesis, a gene associated with B lymphocytes, a gene associated with T lymphocytes, a gene associated with a lysosome, a gene associated with MHC, a gene associated with an immunoproteasome, a gene associated with an NADPH oxidase pathway, a gene associated with an IFN gamma pathway, a gene associated with apoptosis, and a gene associated with integrin and an extracellular matrix;
- comparing the magnitude of gene expression of the combination of gene in the post-transplantation sample with the magnitude of gene expression of the same combination of genes in a control sample;
- and
- determining whether the combination of genes is up-regulated relative to the control sample, wherein up-regulation of the combination of genes indicates that the subject is likely to experience transplant rejection, thereby assessing the onset of rejection of the transplanted organ in the subject.
A method of monitoring transplant rejection in a subject comprising:
- taking as a baseline value the magnitude of gene expression of a combination of a plurality of genes in a sample obtained from a transplanted subject who is known not to develop rejection;
- detecting a magnitude of gene expression corresponding to the combination of a plurality of genes in a sample obtained from a patient post-transplantation;
- and
- comparing the first value with the second value, wherein a first value lower or higher than the second value predicts that the transplanted subject is at risk of developing rejection, wherein the plurality of genes are defined in Table 3.
A method of monitoring transplant rejection in a subject comprising
- detecting a magnitude of gene expression corresponding to a combination of a plurality of genes from a sample obtained from a donor subject at the day of transplantation;
- detecting a magnitude of gene expression corresponding to the plurality of genes from a sample obtained from a recipient subject post-transplantation;
- comparing the first value with the second value, wherein a first value lower or higher than the second value predicts that the recipient subject is at risk of developing rejection;
- wherein the plurality of genes are as defined in Table 3.
A method for monitoring transplant rejection in a subject at risk thereof comprising
- obtaining a pre-administration sample from a transplanted subject prior to administration of a rejection inhibiting agent;
- detecting the magnitude of gene expression of a plurality of genes in the pre-administration sample;
- obtaining one or more post-administration samples from the transplanted subject;
- detecting the magnitude of gene expression of a plurality of genes in the post-administration sample or samples,
- comparing the magnitude of gene expression of the plurality of genes in the pre-administration sample with the magnitude of gene expression in the post-administration sample or samples, and
- adjusting the agent accordingly, wherein the plurality of genes are defined in Table 3.
A method for preventing, inhibiting, reducing or treating transplant rejection in a subject in need of such treatment comprising administering to the subject a compound that modulates the synthesis, expression or activity of one or more genes identified in Table 3, or the synthesis, expression or activity of a product of one or more genes identified in Table 3.
A method for identifying agents for use in the prevention, inhibition, reduction or treatment of transplant rejection comprising monitoring the level of gene expression of one or more genes identified in Table 3, or the synthesis, expression or activity of a product of one or more genes identified in Table 3.
44-45. (canceled)
A method of monitoring transplant rejection in a subject comprising taking as a baseline value the magnitude of gene expression corresponding to a combination of a plurality of genes in a sample of a transplanted subject who is known not to develop rejection;
- detecting a magnitude of gene expression corresponding to the combination of the plurality of genes in an sample obtained from a subject post-transplantation;
- and
- comparing the first value with the second value, wherein a first value lower or higher than the second value predicts that the transplanted subject is at risk of developing rejection, wherein the plurality of genes are as defined in Table 3.
Dependencies are inferred from the claim text.