Methods for diagnosing and reducing incidences of cardiac allograft rejection

A noninvasive method of diagnosing early onset of chronic allograft rejection, the method comprising the steps of:

• measuring an amount of a first natural anti-phosphorylcholine antibody within at least one biological sample from a cardiac allograft recipient;
• comparing the amount of the first anti-phosphorylcholine natural antibody in the biological sample with the amount of the first anti-phosphorylcholine natural antibody in a control sample;
• analyzing the at least one biological sample for one or more biomarkers indicative of the presence of fibrin deposits within the cardiac allograft microvasculature;
• wherein a decrease in the amount of the first anti-phosphorylcholine natural antibody in the sample from the cardiac allograft recipient as compared to the amount of the first anti-phosphorylcholine natural antibody in the control sample indicates a diagnosis of the allograft recipient being either at-risk for developing the fibrin deposits within the cardiac allograft vasculature indicative of chronic allograft rejection;
• and
• wherein detection of the one or more biomarkers in the at least one biological sample indicates that the cardiac allograft recipient is at-risk for or developing the fibrin deposits within the cardiac allograft vasculature indicative of cardiac allograft vasculopathy;
• wherein the one or more biomarkers is/are selected from the group consisting of an elevated level of cardiac troponin I, reduced anticoagulant and fibrinolytic capacities of the serum, detection of up-regulation of endothelial intercellular adhesion molecule-1 (ICAM-1) expression, and detection of an elevated nuclear factor-kappa B (NF-KB) nuclear expression;
• and
• wherein if the cardiac allograft recipient is at-risk of developing the fibrin deposits within the cardiac allograft vasculature indicative of cardiac allograft vasculopathy, the method further comprises the step of:
• administering a therapeutically effective amount of phosphorylcholine to the cardiac allograft recipient to treat and/or prevent cardiac allograft vasculopathy, which selectively enhances a natural antibody-mediated innate immune response in the cardiac allograft recipient by increasing levels of immunoglobulin M and/or immunoglobulin G anti-phosphorylcholine natural antibodies in an allograft recipient's serum.

A noninvasive method of screening a cardiac allograft recipient for being at-risk for developing cardiac allograft vasculopathy (CAV), Major Cardiac Events (MACE), and Graft Failure Due to CAV (GFDCAV), the method comprising the steps of:

• measuring an amount of a first anti-phosphorylcholine natural antibody within at least one biological sample from a cardiac allograft recipient;
• comparing the amount of the first anti-phosphorylcholine natural antibody in the biological sample with the amount of the first natural antibody in a control sample;
• wherein a decrease in the amount of the first anti-phosphorylcholine natural antibody in the biological sample from the cardiac allograft recipient as compared to the amount of the first anti-phosphorylcholine natural antibody in the control sample indicates a diagnosis of the allograft recipient being either at-risk for or developing cardiac allograft vasculopathy (CAV), Major Cardiac Events (MACE), and Graft Failure Due to CAV (GFDCAV);
• and
• administering a therapeutically effective amount of phosphorylcholine to the cardiac allograft recipient to treat and/or prevent cardiac allograft vasculopathy (CAV), which selectively enhances a natural antibody-mediated immune response, further comprising increasing levels of immunoglobulin M and/or immunoglobulin G anti-phosphorylcholine natural antibodies in the allograft recipient's serum, to reduce risk factors of Cardiac Allograft Vasculopathy (CAV), Major Cardiac Events (MACE), and Graft Failure Due to CAV (GFDCAV).