The Presence of Autoantibodies to Misfolded Transthyretin in Patients with Transthyretin Cardiac Amyloidosis

Introduction: The purpose of the trial was to evaluate the presence of autoantibodies to misfolded Transthyretin (mis-TTR) in patients with cardiac amyloidosis (CA) and to study their potential functional properties.

ATTR cardiac amyloidosis typically occurs when mis -TTR deposits in extracellular space. Altered self -proteins trigger humoral and cellular autoimmune responses.
We hypothesize that the presence of circulating mis- TTR is associated with the occurrence of autoantibodies reactive with. Furthermore, we wished to study their potential functional properties.

Materials and Methods: We studied a population of patients with ATTR cardiac amyloidosis and a control group comprising of patients with heart failure and preserved ejection fraction. Patients with cardiac amyloidosis were diagnosed with PYP scintigraphy, in the absence of monoclonal gammopathy.

ELISA was employed for the detection of autoantibodies reactive with mis- TTR.

Purified anti- TTR antibodies were evaluated for their ability to promote uptake of fluorescently mis- TTR to macrophages.

Results and Discussion: Patients with ATTR- CA exhibited significantly higher titers of autoantibodies to mis- TTR compared with controlled heart failure patients. These autoantibodies appear to have protective effects by enhancing the uptake of mis-TTR to human myelomonocytic cell lines.

Conclusion: This is the first study to show the presence of natural autoantibodies to misfolded TTR that appear to possess protective properties from TTR mediated toxicity.