Ventricular assist device elicits serum natural IgG that correlates with the development of primary graft dysfunction following heart transplantation

Sarah B. See, Kevin J. Clerkin, Peter J. Kennel, Feifan Zhang, Matthew P. Weber, Kortney J. Rogers, Debanjana Chatterjee, Elena R. Vasilescu, George Vlad, Yoshifumi Naka, Susan W. Restaino, Maryjane A. Farr, Veli K. Topkara, Paolo C. Colombo, Donna M. Mancini, P. Christian Schulze, Bruce Levin, Emmanuel Zorn

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

Background Pre-transplant sensitization is a limiting factor in solid-organ transplantation. In heart transplants, ventricular assist device (VAD) implantation has been associated with sensitization to human leukocyte antigens (HLA). The effect of VAD on non-HLA antibodies is unclear. We have previously shown that polyreactive natural antibodies (Nabs) contribute to pre-sensitization in kidney allograft recipients. Here we assessed generation of Nabs after VAD implantation in pre-transplant sera and examined their contribution to cardiac allograft outcome. Methods IgM and IgG Nabs were tested in pre-transplant serum samples collected from 206 orthotopic heart transplant recipients, including 128 patients with VAD (VAD patients) and 78 patients without VAD (no-VAD patients). Nabs were assessed by testing serum reactivity to apoptotic cells by flow cytometry and to the generic oxidized epitope, malondialdehyde, by enzyme-linked immunosorbent assay. Results No difference was observed in serum levels of IgM Nabs between VAD and no-VAD patients. However, serum IgG Nabs levels were significantly increased in VAD compared with no-VAD patients. This increase was likely due to the presence of the VAD, as revealed by lower serum IgG Nabs levels before implantation. Elevated pre-transplant IgG Nabs level was associated with development of primary graft dysfunction (PGD). Conclusions Our study demonstrates that VAD support elicits IgG Nabs reactive to apoptotic cells and oxidized epitopes. These findings further support broad and non-specific B-cell activation by VAD, resulting in IgG sensitization. Moreover, the association of serum IgG Nabs levels with development of PGD suggests a possible role for these antibodies in the inflammatory reaction accompanying this complication.

Original languageEnglish (US)
Pages (from-to)862-870
Number of pages9
JournalJournal of Heart and Lung Transplantation
Volume36
Issue number8
DOIs
StatePublished - Aug 2017
Externally publishedYes

Keywords

  • B1 cells
  • natural polyreactive antibodies
  • non-HLA antibodies
  • orthotopic heart transplant
  • primary graft dysfunction
  • sensitization
  • ventricular assist device

ASJC Scopus subject areas

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

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