Use of Eomesodermin to determine risk of allograft rejection

Patent metadata

Field	Value
Publication number	US-11022601-B2
Application number	US-201615545414-A
Country	US
Kind code	B2
Filing date	Jan 22, 2016
Priority date	Jan 23, 2015
Publication date	Jun 1, 2021
Grant date	Jun 1, 2021

Abstract

Pre-existing alloreactive memory T cells are a major barrier to the induction of allograft tolerance in organ transplant recipients. The use of Eomesodermin (Eomes) expression in memory T cells to determine the risk of allograft rejection in a subject is described. Also described is the use of Eomes expression in memory T cells of transplant recipients to modify immunosuppressive therapy.

First claim

The invention claimed is:

1. A method of determining the risk of allograft rejection in a subject who has received an allograft, comprising:
obtaining a peripheral blood mononuclear cell (PBMC) sample from the subject before the subject received the allograft and obtaining a PBMC sample from the subject after the subject received the allograft;
isolating memory T cells from the PBMC samples, wherein isolating memory T cells comprises isolating cells that express at least one memory T cell marker selected from CD95 and CD45RO;
measuring expression of Eomesodermin (Eomes) in the memory T cells isolated from the PBMC samples;
detecting an increase in expression of Eomes in the memory T cells isolated from the sample obtained after the subject received the allograft compared to expression of Eomes in the memory T cells isolated from the sample obtained before the subject received the allograft, thereby determining an increased risk for allograft rejection in the subject; and
modifying a treatment administered to the subject with the increased risk for allograft rejection after receiving the allograft relative to a current therapy, wherein the treatment administered to the subject comprises an immunosuppressive therapy and the modifying comprises increasing a dose and/or frequency of the immunosuppressive therapy relative to a value administered before receiving the allograft, administering an alternative immunosuppressive therapy relative to the immunosuppressive therapy administered before receiving the allograft, or administering an additional immunosuppressive therapy to the subject.

2. The method of claim 1 , wherein isolating memory T cells further comprises detecting the absence of expression of at least one naïve or effector T cell marker.

3. The method of claim 1 , wherein measuring expression of Eomes in the memory T cells isolated from the samples comprises simultaneously detecting expression of Eomes and the at least one memory T cell marker selected from CD95 and CD45RO.

4. The method of claim 3 , further comprising simultaneously detecting the absence of expression of at least one naïve or effector T cell marker.

5. The method of claim 2 , wherein the at least one naïve or effector T cell marker is selected from CD28 and CD45RA.

6. The method of claim 1 , wherein the allograft comprises kidney tissue.

7. A method of treating a subject who has received an allograft, comprising:
administering an immunosuppressive therapy to the subject;
providing a peripheral blood mononuclear cell (PBMC) sample obtained from the subject before administration of the immunosuppressive therapy and a PBMC sample obtained from the subject after administration of the immunosuppressive therapy;
isolating memory T cells from the PBMC samples, wherein isolating memory T cells comprises isolating cells that express at least one memory T cell marker selected from CD95 and CD45RO;
detecting an increase in expression of Eomesodermin (Eomes) in the memory T cells isolated from the sample obtained after administration of the immunosuppressive therapy compared to the sample obtained before administration of immunosuppressive therapy; and
modifying the immunosuppressive therapy administered to the subject, wherein modifying the immunosuppressive therapy comprises increasing the dose and/or frequency of the immunosuppressive therapy administered to the subject, or administering to the subject an alternative or additional immunosuppressive therapy.

8. The method of claim 7 , wherein isolating memory T cells further comprises detecting the absence of expression of at least one naïve or effector T cell maker.

9. The method of claim 7 , wherein detecting expression of Eomes in the isolated memory T cells comprises simultaneously detecting expression of Eomes and the at least one memory T cell marker selected from CD95 and CD45RO.

10. The method of claim 9 , further comprising simultaneously detecting the absence of expression of at least one naïve or effector T cell marker.

11. The method of claim 10 , wherein the at least one naïve or effector T cell marker is selected from CD28 and CD45RA.

12. The method of claim 7 , wherein the allograft comprises kidney tissue.

Assignees

• Univ Of Pittsburgh—Of The Commonwealth System Of Higher Education

Inventors

• Ezzelarab Mohamed B
• Thomson Angus W

Classifications

• G01N2333/4703

  Regulators; Modulating activity · CPC title

• G01N33/5005 Primary

  involving human or animal cells (immunoassay G01N33/56966; immunoassays of protozoa G01N33/56905; protozoa in screening assays C12Q1/025) · CPC title