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

JOURNAL OF HEART AND LUNG TRANSPLANTATION

卷:36

Article

See, Sarah B.¹  Clerkin, Kevin J.²  Kennel, Peter J.¹  Zhang, Feifan³  Weber, Matthew P.²  Rogers, Kortney J.¹  Chatterjee, Debanjana¹  Vasilescu, Elena R.⁴  Vlad, George⁴  Naka, Yoshifumi⁵  Restaino, Susan W.²  Farr, Maryjane A.²  Topkara, Veli K.²  Colombo, Paolo C.²  Mancini, Donna M.²  Schulze, P. Christian²  Levin, Bruce³  Zorn, Emmanuel¹ 

[1] Columbia Univ, Med Ctr, Columbia Ctr Translat Immunol, 630 West 168th St,Black Bldg,Mailbox 127, New York, NY 10032 USA

[2] Columbia Univ, Med Ctr, Dept Med, Div Cardiol, New York, NY USA

[3] Columbia Univ, Mailman Sch Publ Hlth, Dept Biostat, New York, NY USA

[4] Columbia Univ, Med Ctr, Dept Surg, Dept Pathol & Cell Biol, New York, NY USA

[5] Columbia Univ, Med Ctr, Dept Surg, Div Cardiothorac Surg, New York, NY USA

关键词: natural polyreactive antibodies;    non-HLA antibodies;    orthotopic heart transplant;    primary graft dysfunction;    sensitization;    ventricular assist device;    B1 cells;   

DOI  :  10.1016/j.healun.2017.03.018

来源: Elsevier

【 摘 要 】

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. Copyright (C) 2017 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

【 授权许可】

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