Cornell University

Cornell Research Foundation Inc.

University of Pennsylvania

Other

Beth Israel Deaconess Medical Center, Inc.

Manikkam Suthanthiran

Ruchuang Ding

Thangamani Muthukumar

Terry Barton Strom

Abraham Shaked

Joseph E Schwartz

Christiane Ferran

Fabien Campagne

Nali Ma

Laurent Mesnard

Mary Maluccio

Miguel C Soares

Lauro Vasconcellos

Yingyos Avihingsanon

This invention describes an allogenomics mismatch scoring method that estimates the genomic incompatibility between potential organ donors and a transplant recipient. The allogenomics method addresses immunological concerns and compares genotype information from matched, or potential, donors and recipients. The allogenomics method uses genomic data available before transplantation and predicts kidney graft function for greater than three years after transplantation. The strength of the inverse correlation between pre-transplantation genomic mismatches and transplant organ function increases with the time after transplantation: a low allogenomics mismatch score correlates with better acceptance and function of a donor transplant over time.

Method to match organ donors to recipients for transplantation

A method for assessing risk of losing a transplanted organ by a patient having an episode of acute rejection of the transplanted organ is described. The method includes obtaining from the patient a cell sample from the transplanted organ or peripheral blood, determining a level of FOXP3 in the cell sample, and correlating the level with the risk of loss of the transplanted organ, wherein, compared to a control level, a significantly greater level of FOXP3 in the cell sample from the transplanted organ or a significantly lower level of FOXP3 in the cell sample from the peripheral blood correlates with a decreased risk of loss of the transplanted organ.

Methods of predicting acute rejection outcomes

Measurement of mRNAs in urinary cells offers a noninvasive means of diagnosing fibrosis in kidneys. One aspect of the invention is a method that includes: (a) measuring quantities of vimentin mRNA, NKCC2 mRNA, and E-cadherin mRNA in a test sample of cells obtained from urine; and (b) determining whether the vimentin mRNA quantity is higher, the NKCC2 mRNA quantity is lower, or the E-cadherin mRNA is higher than in healthy urinary cells; and thereby detecting that the sample is a fibrotic kidney sample. Step (a) can also include measuring the quantity of RNA expressed by a housekeeping gene (e.g., 18S rRNA). The quantities of vimentin mRNA, NKCC2 mRNA, and E-cadherin mRNA can be normalized against the quantity of housekeeping gene RNA.

Non-invasive method of diagnosing renal fibrosis

Non-invasive methods for detecting, predicting, and/or monitoring differential diagnosis of kidney transplant dysfunction in kidney transplant patients are described.

Urine mRNA profile and acute dysfunction of kidney allograft

The invention relates to, among other things, a method for assessing risk of organ rejection in a patient having a transplanted organ. The method includes measuring an amount of expression of a small non-coding marker RNA in a biological sample from the patient. The method further includes comparing the measured amount of expression of the small non-coding marker RNA in the patient to a reference amount of expression of the small non-coding marker RNA. In another aspect, the invention relates to kits for assessing risk of organ rejection in a patient having a transplanted organ.

Method to assess human allograft status from microrna expression levels

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, CD3&#x3b5; 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.

Methods to detect, treat and prevent acute cellular rejection in kidney allografts

In some embodiments, a method to detect acute rejection in allograft from is described. In some embodiments, a method to anticipate an episode of acute rejection in allografts is also described. In some embodiments, a kit for detecting or predicting acute transplant rejection of a transplanted organ is described.

Methods and compositions to predict and detect acute rejection

The invention relates to methods of evaluating transplant rejection in a host comprising determining a heightened magnitude of gene expression of genes in rejection-associated gene clusters. The disclosed gene clusters include genes that are substantially co-expressed with cytotoxic lymphocyte pro-apoptotic genes, cytoprotective genes and several other cytokine and immune cell genes.

Measurement of protective genes in allograft rejection

The invention provides a method for reducing formation or progression of neoplasms associated with immunosuppressive therapy in a mammal, the method comprising treating the mammal with an effective amount of an angiotensin II inhibitor. In addition the invention provides a method of preventing or treating a neoplasm in a mammal, the method includes treating the mammal with an effective amount of an angiotensin II inhibitor where the treatment is not associated with chemotherapy or radiation therapy. Also provided are compositions comprising an angiotensin II inhibitor and an immunosuppressive agent such as cyclosporin or FK506. The angiotensin II inhibitor of the invention includes proteins and polypeptides that bind angiotensin II receptors, anti-angiotensin II antibodies, angiotensin II receptors and fragments thereof. In another aspect the invention provides methods for identifying compounds capable of inhibiting the formation or proliferation of tumors in a mammal undergoing immunosuppressive therapy.

Use of angiotensin II inhibitors to prevent malignancies associated with immunosuppression

The invention relates to methods of evaluating transplant rejection in a host comprising determining a heightened magnitude of gene expression of two out of three immune activation marker genes perforin, granzyme B and Fas ligand, in a tissue biopsy or peripheral blood mononuclear cell sample, particularly using reverse transcription polymerase chain reaction; methods of assessing antirejection therapy; and kits for use in evaluating transplant rejection.

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Scarsdale, NY, United States of America

Manikkam Suthanthiran