Continuous Intermittent Intravenous Immunoglobulin in Heart Transplant Recipients with Elevated Donor-Specific Antibody Levels

Abstract

<h3>Purpose</h3> Donor-specific antibodies (DSA) develop following heart transplantation (HT), and are associated with antibody-mediated rejection (AMR). However, treatment of persistently elevated DSA levels remains unclear. We aimed to evaluate the use of intermittent intravenous immunoglobulin (IVIg) for the treatment of elevated DSA. <h3>Methods</h3> We identified all adult HT recipients receiving monthly IVIg infusions between September 2019 and October 2020. Patient information including serial DSA levels, as well as hemodynamic and echocardiographic characteristics, were collected from the electronic health record. <h3>Results</h3> The cohort included 17 patients with a mean age of 57 +/- 15 years, 65% were male, & median time from HT was 48 months. 7 patients had prior biopsy-proven AMR, 7 had high mean fluorescence intensity (MFI) DSA alone, and 3 had allograft dysfunction without proven etiology. The average left ventricular ejection fraction (LVEF) prior to IVIg was 50% +/- 14%. Prior to intermittent IVIg 12 patients (71%) received an additional immunosuppressive agent (thymoglobulin, bortezomib, rituximab, belatacept), while 11 of them (65%) also received plasmapheresis. The mean duration of IVIg following pAMR was 7.6 +/- 7 months. DSA MFI decreased by 27% in patients with confirmed diagnosis of AMR and by 10% in those with elevated DSA alone after initiating intermittent IVIg (figure). Both LVEF and cardiac index improved in all three groups following initiation of IVIg infusions. Pulmonary capillary wedge pressure (PCWP) decreased in the elevated DSA and allograft dysfunction groups while it increased in the AMR group. Seven patients were admitted for suspected rejection after starting treatment. <h3>Conclusion</h3> DSA MFI declined and LVEF improved following initiation of intermittent IVIg infusions. Further study is needed to determine whether IVIg can prevent <i>de novo</i> or recurrent AMR.