Methods to detect, treat and prevent acute cellular rejection in kidney allografts
AssigneesCornell University, The Trustees of the University of Pennsylvania
InventorsManikkam Suthanthiran, Ruchuang Ding, Joseph E. Schwartz, Abraham Shaked
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Abstract
Methods for prevention and treatment of kidney transplant rejection are described that involve determination, analysis and computation of a 3-gene molecular signature of levels of specific RNAs (IP-10 mRNA, CD3ε mRNA, and 18S rRNA) in urinary sample cells. The methods and devices described herein are diagnostic and prognostic of acute cellular rejection in kidney allografts.
Claims17
A method for detecting developing or existing dysfunction or rejection of a kidney transplant in a subject from a urine sample obtained from the subject comprising:
- (a) determining an absolute urinary CD3ε mRNA copy number per microgram of total RNA in the urine sample;
- (b) determining an absolute urinary IP-10 mRNA copy number per microgram of total RNA in the urine sample;
- (c) determining an absolute urinary 18S rRNA copy number per microgram of total RNA times 10−6 in the urine sample;
- (d) ascertaining a diagnostic signature of developing or existing dysfunction or rejection of a kidney transplant in the subject with the following algorithm:
- signature=−6.1487+0.8534 log10(CD3ε/18S)+0.6376 log10(IP-10/18S)+1.6464 log10(18S)
- where:
- CD3ε is an absolute urinary CD3ε mRNA copy number per microgram of total RNA in the urine sample;
- IP-10 is an absolute urinary IP-10 mRNA copy number per microgram of total RNA in the urine sample;
- and
- 18S is an absolute urinary 18S rRNA copy number per microgram of total RNA in the urine sample times 10−6;
- to thereby detect a developing or existing dysfunction or rejection of a kidney transplant in the subject.
A composition consisting essentially of one or more probes or primers for each of CD3ε mRNA, IP-10 mRNA, and 18S rRNA;
- and an optional control or reference probe or primer.
A device consisting essentially of one or more probes or primers for each of CD3ε mRNA, IP-10 mRNA, and 18S rRNA covalently linked to a solid support, and an optional control or reference probe or primer covalently linked to a solid support.
A kit c consisting essentially of one or more probes or primers for each of CD3ε mRNA, IP-10 mRNA, and 18S rRNA, and instructions for use in detecting potential or existing dysfunction or rejection of a kidney transplant in a subject.
Dependencies are inferred from the claim text.