Method to detect the onset and to monitor the recurrence of chronic graft versus host disease in tranplantation patients

Abstract

The described invention comprises a method for detecting the onset or monitoring the recurrence of chronic graft versus host disease (cGVHD) in a transplantation patient. The method comprises isolating peripheral blood mononuclear cells (PBMCs) from the transplantation patient and analyzing the isolated PBMCs to detect a biomarker specific for a donor cell. The detection of the biomarker is indicative of the onset or recurrence of cGVHD in the transplantation patient.

What is claimed is: 
     
         1 . A method for warning of onset of chronic graft versus host disease (cGvHD) prior to appearance of symptoms of cGvHD in a patient following a hematopoietic cell transplantation therapy with a hematopoietic cell allograft, comprising:
 (a) isolating peripheral blood mononuclear cells (PBMCs) from the patient at a time after the therapy;   (b) analyzing the isolated PBMCs, and specifically detecting a first biomarker expressed by circulating cells of the patient that reacts with a second biomarker expressed by genetically distinct cells,   wherein the detecting of the cells that express the first biomarker indicates likely imminent onset of cGVHD in the patient; and   (c) initiating immune therapy to mitigate symptoms of cGvHD resulting from the transplant.   
     
     
         2 . The method according to  claim 1 , wherein the circulating cells expressing the first biomarker are B lymphocytes with receptors that detect the first biomarker. 
     
     
         3 . The method according to  claim 1 , wherein the circulating cells are derived from the hematopoietic cell allograft. 
     
     
         4 . The method according to  claim 2 , wherein the first biomarker is an antibody, the hematopoietic cell allograft contains cells that express the antibody, and the antibody reacts with the second biomarker expressed by the patient's cells. 
     
     
         5 . The method according to  claim 4 , wherein the second biomarker is a Y-chromosome encoded H-Y antigen. 
     
     
         6 . The method according to  claim 5 , wherein the H-Y antigen is DBY-2. 
     
     
         7 . The method according to  claim 5 , wherein the recipient patient is male, the recipient's cells express the second biomarker, and the second biomarker is the Y-chromosome encoded H-Y antigen, the donor is female, the donor's cells express the first biomarker, and the first biomarker is an antibody, which binds to the second biomarker, which is the H-Y antigen expressed by the patient's cells. wherein the recipient patient and donor are genetically distinct. 
     
     
         8 . The method according to  claim 7 , wherein the donor's cells that express the first biomarker are B lymphocytes. 
     
     
         9 . The method according to  claim 8 , wherein phenotype of the B lymphocytes is CD19 + . 
     
     
         10 . The method according to  claim 1 , wherein the time after therapy for detecting the first biomarker expressed by circulating cells of the patient is within 1 year after transplantation. 
     
     
         11 . The method according to  claim 1 , wherein the time after therapy for detecting the first biomarker expressed by circulating cells of the patient is within 180 days after transplantation. 
     
     
         12 . The method according to  claim 1 , wherein the time after therapy for detecting the first biomarker expressed by circulating cells of the patient is within 155 days after transplantation. 
     
     
         13 . The method according to  claim 1 , wherein time after therapy for detecting of the first biomarker expressed by circulating cells of the patient is within 90 days after transplantation. 
     
     
         14 . The method according to  claim 1 , wherein detecting of the first biomarker expressed by circulating cells of the patient precedes development of circulating antibodies to a donor cell antigen in the patient. 
     
     
         15 . The method according to  claim 1 , wherein analyzing step (b) is performed using flow cytometry. 
     
     
         16 . A method for warning of recurrence of chronic graft versus host disease (cGvHD) prior to appearance of symptoms of cGvHD in a patient who, following hematopoietic cell transplantation therapy with a hematopoietic cell allograft, developed and was treated for cGvHD, which is in remission, comprising:
 (a) isolating peripheral blood mononuclear cells (PBMCs) from the patient at a time after the therapy;   (b) analyzing the isolated PBMCs, and specifically detecting a first biomarker expressed by circulating cells of the patient that reacts with a second biomarker expressed by genetically distinct cells,   wherein the detecting of the cells that express the first biomarker indicates likely imminent onset of cGvHD in the patient; and   (c) initiating immune therapy to treat the recurrence of the cGvHD resulting from the transplant.   
     
     
         17 . The method according to  claim 16 , wherein the circulating cells expressing the first biomarker are B lymphocytes with receptors that detect the first biomarker. 
     
     
         18 . The method according to  claim 16 , wherein the circulating cells are derived from the hematopoietic cell allograft. 
     
     
         19 . The method according to  claim 17 , wherein the first biomarker is an antibody, the hematopoietic cell allograft contains cells that express the antibody, and the antibody reacts with the second biomarker expressed by the patient's cells. 
     
     
         20 . The method according to  claim 19 , wherein the second biomarker is a Y-chromosome encoded H-Y antigen. 
     
     
         21 . The method according to  claim 20 , wherein the H-Y antigen is DBY-2. 
     
     
         22 . The method according to  claim 20 , wherein the recipient patient is male, the recipient's cells express the second biomarker, and the second biomarker is the Y-chromosome encoded H-Y antigen, the donor is female, the donor's cells express the first biomarker, and the first biomarker is an antibody, which binds to the second biomarker, which is the H-Y antigen expressed by the patient's cells. wherein the recipient patient and donor are genetically distinct. 
     
     
         23 . The method according to  claim 22 , wherein the donor's cells that express the first biomarker are B lymphocytes. 
     
     
         24 . The method according to  claim 23 , wherein phenotype of the B lymphocytes is CD19 + . 
     
     
         25 . The method according to  claim 16 , wherein the time after therapy for detecting the first biomarker expressed by circulating cells of the patient is within 1 year after transplantation. 
     
     
         26 . The method according to  claim 16 , wherein the time after therapy for detecting the first biomarker expressed by circulating cells of the patient is within 180 days after transplantation. 
     
     
         27 . The method according to  claim 16 , wherein the time after therapy for detecting the first biomarker expressed by circulating cells of the patient is within 155 days after transplantation. 
     
     
         28 . The method according to  claim 16 , wherein time after therapy for detecting of the first biomarker expressed by circulating cells of the patient is within 90 days after transplantation. 
     
     
         29 . The method according to  claim 16 , wherein detecting of the first biomarker expressed by circulating cells of the patient precedes development of circulating antibodies to a donor cell antigen in the patient. 
     
     
         30 . The method according to  claim 16 , wherein analyzing step (b) is performed using flow cytometry.