Assessment and reduction of risk of graft-versus-host disease

摘要

Methods of assessing and reducing risk of graft versus host disease (GVHD) based on gene expression profiling are described, as well as methods of selecting a suitable transplant donor. Corresponding reagents and kits are also described.

主权项

1. A method of treating a subject in need of a bone marrow or hematopoietic cell transplant, said method comprising:
assessing the risk of a candidate human transplant donor of inducing graft versus host disease (GVHD) in a human transplant recipient by a method comprising: (a) measuring the level or amount of a TCIRG1 mRNA in a CD4+ and/or CD8+ T cell sample from said candidate human transplant donor to obtain a candidate gene expression profile by: (i) obtaining mRNA from said sample; (ii) generating cDNA from the obtained mRNA; (iii) amplifying the cDNA encoding TCIRG1; and (iv) measuring the level of said cDNA encoding TCIRG1; (b) comparing said candidate gene expression profile to a corresponding reference gene expression profile, wherein said reference gene expression profile comprises a reference expression value for a TCIRG1 mRNA, said reference gene expression profile being derived from a comparison of: (i) a GVHD+ expression profile comprising a GVHD+ expression value for a TCIRG1 mRNA derived from a CD4+ and/or CD8+ T cell sample obtained from a human transplant donor known to have induced GVHD in a human transplant recipient with (ii) a GVHD− expression profile comprising a GVHD− expression value for a TCIRG1 mRNA derived from a CD4+ and/or CD8+ T cell sample obtained from a human transplant donor known to have not induced GVHD in a human transplant recipient, whereby said reference expression value is determined as being (A) the level of expression midway between said GVHD+ expression value and said GVHD− expression value-whereby the midway level separates a GVHD+ class comprising said GVHD+ expression value from a GVHD− class comprising said GVHD− expression value; (B) the level of expression between said GVHD+ expression value and said GVHD− expression value defined as separating expression values into GVHD+ and GVHD− classes on the basis of discriminatory analysis; or (C) both (A) and (B); (c) assessing risk of said candidate human transplant donor of inducing GVHD in a human transplant recipient in accordance with said comparing step of said candidate gene expression profile with said reference gene expression profile, wherein (i) a candidate expression value within said GVHD− class is indicative that said candidate human transplant donor has a reduced risk of inducing GVHD in a transplant recipient, and (ii) a candidate expression value within said GVHD+ class is indicative that said candidate human transplant donor has an increased risk of inducing GVHD in a transplant recipient; and (d) either (i) when said candidate human transplant donor has a reduced risk of inducing GVHD in a transplant recipient, transplanting said subject in need of a bone marrow or hematopoietic cell transplant with a bone marrow or hematopoietic cell transplant from said candidate human transplant donor under a standard or less aggressive anti-rejection treatment regimen; or (ii) when said candidate human transplant donor has an increased risk of inducing GVHD in a transplant recipient, transplanting said subject in need of a bone marrow or hematopoietic cell transplant with (a) a bone marrow or hematopoietic cell transplant from said candidate human transplant donor under an aggressive anti-rejection treatment regimen; or (b) a bone marrow or hematopoietic cell transplant from another candidate human transplant donor.