Ventricular assist device elicits serum natural IgG that correlates with the development of primary graft dysfunction following heart transplantation
Copyright © 2017 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2017 |
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| Erschienen: |
2017 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:36 |
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| Enthalten in: |
The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation - 36(2017), 8 vom: 01. Aug., Seite 862-870 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
See, Sarah B [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 11.06.2018 Date Revised 09.01.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.healun.2017.03.018 |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM271184450 |
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| 041 | |a eng | ||
| 100 | 1 | |a See, Sarah B |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Ventricular assist device elicits serum natural IgG that correlates with the development of primary graft dysfunction following heart transplantation |
| 264 | 1 | |c 2017 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 11.06.2018 | ||
| 500 | |a Date Revised 09.01.2021 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2017 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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) | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Multicenter Study | |
| 650 | 4 | |a B1 cells | |
| 650 | 4 | |a natural polyreactive antibodies | |
| 650 | 4 | |a non-HLA antibodies | |
| 650 | 4 | |a orthotopic heart transplant | |
| 650 | 4 | |a primary graft dysfunction | |
| 650 | 4 | |a sensitization | |
| 650 | 4 | |a ventricular assist device | |
| 650 | 7 | |a Antibodies, Anti-Idiotypic |2 NLM | |
| 650 | 7 | |a Biomarkers |2 NLM | |
| 650 | 7 | |a Epitopes |2 NLM | |
| 650 | 7 | |a Immunoglobulin G |2 NLM | |
| 700 | 1 | |a Clerkin, Kevin J |e verfasserin |4 aut | |
| 700 | 1 | |a Kennel, Peter J |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Feifan |e verfasserin |4 aut | |
| 700 | 1 | |a Weber, Matthew P |e verfasserin |4 aut | |
| 700 | 1 | |a Rogers, Kortney J |e verfasserin |4 aut | |
| 700 | 1 | |a Chatterjee, Debanjana |e verfasserin |4 aut | |
| 700 | 1 | |a Vasilescu, Elena R |e verfasserin |4 aut | |
| 700 | 1 | |a Vlad, George |e verfasserin |4 aut | |
| 700 | 1 | |a Naka, Yoshifumi |e verfasserin |4 aut | |
| 700 | 1 | |a Restaino, Susan W |e verfasserin |4 aut | |
| 700 | 1 | |a Farr, Maryjane A |e verfasserin |4 aut | |
| 700 | 1 | |a Topkara, Veli K |e verfasserin |4 aut | |
| 700 | 1 | |a Colombo, Paolo C |e verfasserin |4 aut | |
| 700 | 1 | |a Mancini, Donna M |e verfasserin |4 aut | |
| 700 | 1 | |a Schulze, P Christian |e verfasserin |4 aut | |
| 700 | 1 | |a Levin, Bruce |e verfasserin |4 aut | |
| 700 | 1 | |a Zorn, Emmanuel |e verfasserin |4 aut | |
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