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Methods of Using FOXP3 Levels to Predict the Outcome of Organs Undergoing Acute Rejection

a technology of foxp3 and organs, applied in the direction of antibody medical ingredients, instruments, drug compositions, etc., can solve the problems of bleeding, arteriovenous fistula, even graft loss, and important risk factor for allograft failure, and achieve the effect of a greater level of foxp3

Inactive Publication Date: 2008-06-05
CORNELL RES FOUNDATION INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0005]The above need has been met by the present invention, which provides in one embodiment a method for assessing risk of losing a transplanted organ by a patient having an episode of acute rejection of the transplanted organ, the method comprising obtaining from the patient a cell sample from the transplanted organ or from 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, or a level of FOXP3 that is not significantly greater in the cell sample from the transplanted organ or a level of FOXP3 that is not significantly lower in the cell sample from peripheral blood correlates with an increased risk of loss of the transplanted organ.

Problems solved by technology

Acute rejection of an organ, transplanted from one human to another, is an important risk factor for allograft failure.
The outcome of acute rejection is, however, difficult to predict.
However, the invasive procedure of allograft biopsy is associated with complications such as bleeding, arteriovenous fistula, and even graft loss.

Method used

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  • Methods of Using FOXP3 Levels to Predict the Outcome of Organs Undergoing Acute Rejection
  • Methods of Using FOXP3 Levels to Predict the Outcome of Organs Undergoing Acute Rejection
  • Methods of Using FOXP3 Levels to Predict the Outcome of Organs Undergoing Acute Rejection

Examples

Experimental program
Comparison scheme
Effect test

example 1

Methods

[0061]Study Cohoris. Urine samples from 83 kidney-transplant recipients were examined. In this group were 36 subjects with graft dysfunction (mean [±SD] creatinine level, 3.6±2.4 mg per deciliter [318.2±212.2 pmol per liter]) and biopsy-confirmed acute rejection (mean age, 41±12 years; 15 men and 21 women; 13 white, 12 black, and 11 with other racial or ethnic backgrounds; with 20 living and 16 deceased donors), 29 subjects with stable allograft function (mean creatinine level, 1.4±0.4 mg per deciliter [123.8±35.4 μmol per liter]) and normal allograft biopsy (mean age, 44±14 years; 15 men and 14 women; 12 white, 4 black, and 13 with other racial or ethnic backgrounds; with 26 living and 3 deceased donors), and 18 subjects with allograft dysfunction (mean creatinine level, 3.1±1.6 mg per deciliter [274.0±141.4 μmol per liter]) and biopsies classified as indicating chronic allograft nephropathy (mean age, 52±12 years; 9 men and 9 women; 9 white, 2 black, and 7 with other racial...

example 2

Levels of FOXP3 mRNA in Urinary Cells

[0066]The log-transformed mean (±SE) ratio of FOXP3 mRNA copies to 18S-rRNA copies in urinary cells was 3.8±0.5 in the 36 subjects with acute rejection and was higher than the levels in both the 18 subjects with chronic allograft nephropathy (1.3±0.7) and the 29 subjects with normal biopsy results (1.6±0.4, P1C, and 1D).

example 3

FOXP3 mRNA Levels and Disease Severity

[0067]We observed a significant inverse relationship between the levels of FOXP3 mRNA and serum creatinine measured during an episode of acute rejection (Spearman's correlation coefficient [rs]=−0.38, P=0.02). By contrast, serum creatinine levels were not significantly related to mRNA levels of CD25 (rs=−0.01, P=0.93), CD3ε (rs=−0.11, P=0.54), or perforin (rs=−0.23, P=0.18) in the acute-rejection group. Also, the mean (±SE) serum creatinine level in the 16 subjects with acute rejection of Banff grade IA (moderate tubulitis) did not differ significantly from that of the 20 subjects with grade IB (severe tubulitis) or more (3.3±0.6 mg per deciliter [291.7±53.0 μmol per liter] as compared with 3.8±0.6 mg per deciliter [318.2±53.0 μmol per liter], P=0.57).

[0068]There was no correlation between the levels of FOXP3 mRNA and serum creatinine that were measured in the group with chronic allograft nephropathy (rs=0.02, P=0.93) or the group with normal bi...

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Abstract

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.

Description

[0001]This application asserts priority to U.S. Provisional Application Ser. No. 60 / 848,040 filed on Sep. 26, 2006, the specification of which is hereby incorporated by reference in its entirety.[0002]The invention described in this application was made with funds from the National Institutes of Health, Grant Numbers RO1 A151652 and AI60706. The United States government has certain rights in the invention.BACKGROUND OF THE INVENTION[0003]Acute rejection of an organ, transplanted from one human to another, is an important risk factor for allograft failure. The outcome of acute rejection is, however, difficult to predict.[0004]Currently, observation of histologic features in allograft tissue obtained by core needle biopsy is the best predictor whether an acute rejection will respond to anti-rejection therapy. However, the invasive procedure of allograft biopsy is associated with complications such as bleeding, arteriovenous fistula, and even graft loss. Thus, there is a need for a non...

Claims

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Application Information

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IPC IPC(8): A61K39/395C12Q1/02C12Q1/68A61P43/00A61K31/56
CPCA61K31/56A61K2039/505C07K16/28G01N33/6872C12Q2600/16G01N2800/245C12Q1/6876C12Q2600/158G01N2333/4703A61P43/00A61K35/14C07K16/2809C12Q2600/106G01N33/6893G01N2800/50G01N2800/52
Inventor SUTHANTHIRAN, MANIKKAM
Owner CORNELL RES FOUNDATION INC
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