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

[0012]In still another aspect, the invention provides methods of screening a compound for activity in inhibiting or treating a kidney transplant rejection or injury. The methods involve (a) administering the compound to a subject having or at risk of developing a kidney transplant rejection; (b) determining expression levels of at least five genes in the subject selected from Tables 1-11 and species variants thereof before and after administering the compound to the subject, (c) determining whether the compound has activity in inhibiting or treating the kidney transplant rejection from a change in expression levels of the genes after administering the compound. In some of these methods, the kidney transplant rejection or injury to be treated or inhibited is AR, ADNR, or CAN. In some methods, step (c) involves for each of the at least five changes assigning a value or designation depending on whether the change in the expression level of the gene relative to one or more reference levels indicating presence or absence of the kidney transplant rejection. Some of these methods further entail determining a combined value or designation for the at le

Problems solved by technology

Unfortunately, graft losses due to allograft dysfunction or other uncertain etio

Images