Tissue molecular signatures of kidney transplant rejection

Abstract

By a genome-wide gene analysis of expression profiles of known or putative gene sequences in kidney biopsy samples, the present inventors have identified a consensus set of gene expression-based molecular biomarkers for distinguishing kidney transplantation patients who have Acute Rejection (AR), Acute Dysfunction No Rejection (ADNR), Chronic Allograft Nephropathy(CAN), or Transplant Excellent / Normal (TX). These molecular biomarkers are useful for diagnosis, prognosis and monitoring of transplantation patients.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application claims the benefit of priority to U.S. application Ser. No. 14 / 481,167, filed Sep. 9, 2014; to International Application No. PCT / US2014 / 054735, filed Sep. 9, 2014; to U.S. Provisional Application No. 62 / 029,038, filed Jul. 25, 2014; to U.S. Provisional Application No. 62 / 001,889, filed May 22, 2014; to U.S. Provisional Application No. 62 / 001,902, filed May 22, 2014; and to U.S. Provisional Application No. 62 / 001,909, filed May 22, 2014, each of which is incorporated by reference herein in their entirety.STATEMENT CONCERNING GOVERNMENT SUPPORT[0002]This invention was made in part with the U.S. government support by the National Institutes of Health Grant No. AI063603. The U.S. Government therefore may have certain rights in the invention.COPYRIGHT NOTIFICATION[0003]Pursuant to 37 C.F.R. §1.71(e), Applicants note that a portion of this disclosure contains material which is subject to copyright protection. The copyright owne...

AI Technical Summary

Benefits of technology

The patent describes methods for predicting, detecting, and monitoring kidney transplant rejection or injury by analyzing the expression levels of genes in a subject's nucleic acids. The methods involve extracting nucleic acids from a sample, such as a kidney biopsy, and detecting changes in the expression levels of at least five genes. These genes include those listed in Tables 7, 8, 9, and 10. The expression levels can be determined at the mRNA or protein level, and the results can be used to prognose, diagnose, or monitor the subject's condition. The invention also provides arrays containing nucleic acid probes or ligands that specifically bind to the genes and proteins involved in the process. Overall, the methods and arrays provide a reliable and sensitive way to monitor and manage kidney transplant health.

Problems solved by technology

Unfortunately, graft losses due to allograft dysfunction or other uncertain etiologies have greatly hampered the therapeutic potential of kidney transplantation.

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