Sum Total MFI of Donor-Specific Antibody - A Prognostic Marker in Antibody-Mediated Rejection

C. Gjelaj, A. Luke, A. Paschenko, R. Fletcher, E. Borukhov, D. Nnani, D. B. Sims, S. Vukelic, O. Saeed, J. Shin, S. Murthy, D. Goldstein, U. P. Jorde, S. R. Patel

Research output: Contribution to journalArticle

Abstract

PURPOSE: Despite recent advances in the understanding of antibody-mediated rejection (AMR), our immunologic and histologic characterization remains imperfect. At present, robust markers of AMR severity are lacking. We examined the association between a readily available index - sum total mean fluorescence intensity (MFI) of all de-novo donor-specific antibodies (DSA) - and clinical outcomes. METHODS: A retrospective chart review of 146 consecutive heart transplant recipients from 2015-2018 was performed. AMR was defined as histologic (activated endothelial cells and intravascular macrophages) or immunopathologic (C4d) evidence on biopsy. DSA and MFI were determined via Luminex. Sum total MFI was calculated as the sum of the MFI of all class I and class II de-novo DSA at the time of initial presentation with AMR. Clinical outcomes through September 15, 2019 were retrieved for the endpoints of death or persistently depressed (>90 days) left ventricular ejection fraction (LVEF) <50%. RESULTS: Within the population of 146 patients, 46 patients developed de-novo DSAs. Of these, 15 met criteria for AMR and 31 did not. AMR patients had a significantly higher sum total MFI than those without clinical AMR. [38,296 ± 26,667 vs. 7,714 ± 6564; p<.001] Of AMR patients, all had at least one Class 2 DSA (13 out of 15 had DQ) while 4 of the patients did not have any Class 1 DSA. All patients were treated according to our institutional protocol with plasmapheresis/IVIG and bortezomib and/or rituximab. Over a mean follow up of 466 days ±356, 5 patients died, while an additional 3 patients had persistently reduced LVEF. Patients were dichotomized according to sum total MFI >30,000; 80% above this value had an adverse event vs. 33% below (p=0.05) Figure 1. The 2011 ISHLT pathologic grading system for AMR had no correlation to outcomes. CONCLUSION: Sum total MFI, a simple and intuitive index, is a prognostic marker of clinical outcomes at the time of AMR. This index may help stratify patients for more aggressive treatment at the time of diagnosis.

ASJC Scopus subject areas

  • Surgery
  • Pulmonary and Respiratory Medicine
  • Cardiology and Cardiovascular Medicine
  • Transplantation

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