Ca125 as an Early Marker for Graft Dysfunction in Antibody-Mediated Rejection: Guidance for Therapy

Abstract

<h3>Introduction</h3> The definition of antibody-mediated rejection (AMR) now recognizes that AMR is a spectrum of immunologic injury ranging from subclinical, histological, immunologic and/or serological findings without graft dysfunction to overt AMR with hemodynamic compromise. The decision to treat AMR takes into account the clinical evidence of rejection, e.g., symptoms or evidence of graft dysfunction, but the definition of hemodynamic/clinical compromise lacks uniformity and no specific criteria are defined. We describe a case report suggesting that carbohydrate antigen 125 (CA125) could be used as a marker for diagnosing clinically significant AMR and for guidance of therapy. <h3>Case Report</h3> A 43 y/o woman, 14 months post-heart transplantation, presented at a routine follow-up with unexplained new sinus tachycardia; otherwise, she was clinically asymptomatic. A recent annual evaluation had revealed normal invasive hemodynamics and coronaries, and no donor specific antibodies (DSAs). Over the next 2 days ECHO deteriorated, with the development of acute severe biventricular dysfunction, although she was "apparently" clinically asymptomatic. Endomyocardial biopsy was classified as pAMR1(H+), ISHLT 1R. De novo DSAs (Class I & II) were detected. Therapy consisted of pulse steroids, followed by thymoglobulin, plasmapheresis, immunoglobulins, rituximab, & photopheresis. Rapidly progressive hemodynamic compromise necessitated ECMO support. Over the following months she developed clinical overt right heart failure, but she gradually recovered fully. CA125 at presentation and through the clinical course and follow up correlated highly with the invasive hemodynamics, ECHO indices, and the clinical course (Figure 1). <h3>Summary</h3> With the recognition of the importance of AMR, there is a need for criteria defining the clinical scenario. The current case suggests that CA125 is a potential marker for clinical significance and could play a role in the guidance of therapy.