Efficacy of Plasmapheresis and Intravenous Immunoglobulin on the Reduction of Donor Specific Antibodies in Heart Transplant Recipients

Abstract

<h3>Purpose</h3> Class II human leukocyte antigen (HLA) donor specific antibodies (DSA) have been associated with a high risk of graft loss and resistance to antibody removal therapy. We aimed to evaluate class II DSA reduction after plasmapheresis (PLEX) and intravenous immunoglobulin (IVIG) in heart transplant recipients (HTR). <h3>Methods</h3> All HTR who received IVIG and PLEX for class II DSAs from 1/1/2017-6/1/2021 were included. Multiorgan, retransplant, and transplant at other centers were excluded. Baseline demographics and mean immunodominant fluorescent intensity (MFI) of DSA were retrieved. The immunodominant DSA was defined as the DSA with highest MFI in any given serum sample. Median MFI reduction rates after PLEX and after IVIG +/- rituximab were calculated. <h3>Results</h3> Thirty encounters involving 21 HTR were identified. At baseline, the immunodominant class II DSA MFI was 9705 (1712,14337.3). Sixteen (76.2%) and five (23.8%) patients had DQ and DR immunodominant DSA, respectively. There was a median reduction of 5325.5 (1539.5,10003.3) in class II DSA MFI following treatment with PLEX from baseline and a subsequent increase of 1235.5 (0,5786) from post PLEX to post IVIG. Overall, there was a reduction from baseline to post PLEX and IVIG of 1864 (1034,3996.8). Four patients (19%) achieved DSA clearance after PLEX, with a median time to clearance of 34 days (26-60) from development. The patients who cleared were all non-African American, had DSAs to only one antigen, were not desensitized pre-transplant, did not have C1q positivity, and had immunodominant MFI <2000. Significantly more patients who failed to clear DSA were taking prednisone (0% vs 76.5%, p=0.005). <h3>Conclusion</h3> PLEX and IVIG can reduce the MFI of class II DSAs in some HTR. PLEX therapy is more efficacious to reduce class II DSA MFI than originally hypothesized. Results from this analysis suggest that DSA to DQ antigens may be less responsive to therapy with PLEX/IVIG at MFI >15,000 or when C1q positive.