Diagnosis and treatment of autoantibody-mediated heart disease

Abstract

Provided herein are, inter alia, methods of diagnosing and treating autoimmune cardiomyopathy in subjects, based upon the detection of IgG4 antibodies to cardiac autoantigens.

What is claimed is: 
     
         1 . A method for diagnosing the presence of, or risk of developing, autoimmune heart disease in a subject, the method comprising:
 providing a sample comprising serum of a subject; and   detecting a level, presence, or absence in the sample of IgG autoantibodies to cardiac troponin I (cTnI),   wherein the presence of IgG autoantibodies to cTnI, e.g., a level above a reference, indicates that the subject has or is at risk of developing autoimmune heart disease.   
     
     
         2 . The method of  claim 1 , wherein the subject has cardiac arrhythmia, idiopathic dilated cardiomyopathy, ischemic cardiomyopathy or unexplained heart failure. 
     
     
         3 . The method of  claim 1 , wherein autoantibodies that bind to an epitope within residues 92-164 of human cTnI are detected. 
     
     
         4 . The method of  claim 3 , wherein autoantibodies that bind to epitopes within residues 92-101, 127-136, or 155-164 of human cTnI are detected 
     
     
         5 . A method for diagnosing the presence of, or risk of developing, autoimmune heart disease in a subject, the method comprising:
 providing a sample comprising cardiac tissue of a subject; and   detecting deposition of IgG autoantibodies on cardiac myocytes in the sample,   wherein the deposition of IgG autoantibodies indicates that the subject has or is at risk of developing autoimmune heart disease.   
     
     
         6 . The method of  claim 5 , wherein the sample is an endomyocardial biopsy. 
     
     
         7 . The method of  claim 5 , wherein the subject has cardiac arrhythmia, idiopathic dilated cardiomyopathy, ischemic cardiomyopathy or unexplained heart failure. 
     
     
         8 . The method of  claim 5 , wherein autoantibodies that bind to an epitope within residues 92-164 of human cTnI are detected. 
     
     
         9 . The method of  claim 8 , wherein autoantibodies that bind to epitopes within residues 92-101, 127-136, or 155-164 of human cTnI are detected 
     
     
         10 . A method for treating autoimmune heart disease, the method comprising:
 selecting a subject who has autoimmune heart disease; and   administering to the subject a therapy that depletes B lymphocytes in the subject.   
     
     
         11 . The method of  claim 10 , wherein selecting a subject comprises:
 providing a sample comprising serum of a subject;   detecting the presence or absence in the sample of IgG autoantibodies to cardiac troponin I (cTnI),   wherein the presence of IgG autoantibodies to cTnI indicates that the subject has or is at risk of developing autoimmune cardiomyopathy;   selecting a subject who has IgG autoantibodies to cTnI.   
     
     
         12 . The method of  claim 11 , wherein the therapy comprises administration of an effective amount of rituximab or other B-cell depleting or B-cell inactivating agents. 
     
     
         13 . The method of  claim 11 , wherein the therapy comprises treating the subject with plasmapheresis or administering intravenous immunoglobulin. 
     
     
         14 . A method for monitoring the efficacy of a treatment for autoimmune heart disease, the method comprising:
 providing a first sample comprising serum of a subject;   detecting a level of IgG autoantibodies to cardiac troponin I (cTnI) in the first sample,   administering a therapy to the subject;   providing a subsequent sample comprising serum of a subject;   detecting a level of IgG autoantibodies to cTnI in the subsequent sample;   comparing the level of IgG autoantibodies to cTnI in the first sample to the level of IgG autoantibodies to cTnI in the subsequent sample,   wherein a decrease in level of IgG4 autoantibodies to cTnI from the first to the subsequent sample indicates that the therapy is effective.   
     
     
         15 . The method of  claim 14 , wherein the therapy comprises administration of an effective amount of rituximab or other B-cell depleting or B-cell inactivating agents. 
     
     
         16 . The method of  claim 14 , wherein the therapy comprises treating the subject with plasmapheresis or administering intravenous immunoglobulin. 
     
     
         17 . The method of  claim 1 , wherein the IgG antibodies are IgG4 subclass. 
     
     
         18 . The method of  claim 5 , wherein the IgG antibodies are IgG4 subclass. 
     
     
         19 . The method of  claim 11 , wherein the IgG antibodies are IgG4 subclass. 
     
     
         20 . The method of  claim 14 , wherein the IgG antibodies are IgG4 subclass.