Elevated Plasma Immunoglobulin Levels Prior to Heart Transplantation Are Associated with Poor Post-Transplantation Survival
by
, , , and
Patricia van den Hoogen
1,2, 
Manon M. H. Huibers
3,4,
Floor W. van den Dolder
3,
Roel de Weger
3,
Erica Siera-de Koning
3,
Marish I. F. Oerlemans
5,
Nicolaas de Jonge
5,
Linda W. van Laake
5,
Pieter A. Doevendans
5,6,7,
Joost. P. G. Sluijter
1,2,
Aryan Vink
3,† and
Saskia C. A. de Jager
1,2,8,*,†
1
Laboratory for Experimental Cardiology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands
2
Circulatory Health Laboratory, Regenerative Medicine Center, Utrecht University, 3584 CX Utrecht, The Netherlands
3
Department of Pathology, Circulatory Health Laboratory, University Medical Center Utrecht, Utrecht University, 3584 CX Utrecht, The Netherlands
4
Department of Genetics, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands
5
Department of Cardiology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands
6
Netherlands Heart Institute (NLHI), 3511 EP Utrecht, The Netherlands
7
Centraal Militair Hospitaal (CMH), 3584 EZ Utrecht, The Netherlands
8
Laboratory of Translational Immunology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Biology 2023, 12(1), 61; https://doi.org/10.3390/biology12010061
Submission received: 3 November 2022
/
Revised: 20 December 2022
/
Accepted: 27 December 2022
/
Published: 30 December 2022
(This article belongs to the Special Issue Immunology and Immunotherapy in Cardiovascular Disease)
Simple Summary
Heart transplantation is the gold standard in selected patients with end-stage heart failure. However, immune responses to the transplanted heart can lead to major complications and graft failure, limiting long-term survival. It has been shown that antibodies targeting the heart are elevated in end-stage heart failure patients and before transplantation of the donor heart. We aimed to determine whether elevated antibody levels before heart transplantation are associated with a poor outcome after transplantation. We measured four general subtypes of antibodies (IgM, IgG1, IgG2, IgG3) in the blood of patients just before the transplantation was performed. We observe that patients with higher levels of IgG1 and IgG2 antibodies tend to reject the transplanted heart more often compared to patients with lower levels of these antibodies. In addition, we observe that IgG1 and IgG2 levels in these patients remain elevated after transplantation. Together our data suggest that a more active adaptive, antibody-mediated, immune system can lead to graft-related complications in cardiac transplant patients. This implies that a subpopulation of heart transplant patients might benefit from expanded immunosuppressive therapy, which includes medications targeting antibody-producing cells.
Abstract
Cardiac allograft vasculopathy (CAV) and antibody-mediated rejection are immune-mediated, long-term complications that jeopardize graft survival after heart transplantation (HTx). Interestingly, increased plasma levels of immunoglobulins have been found in end-stage heart failure (HF) patients prior to HTx. In this study, we aimed to determine whether increased circulating immunoglobulin levels prior to transplantation are associated with poor post-HTx survival. Pre-and post-HTx plasma samples of 36 cardiac transplant recipient patients were used to determine circulating immunoglobulin levels. In addition, epicardial tissue was collected to determine immunoglobulin deposition in cardiac tissue and assess signs and severity of graft rejection. High levels of IgG1 and IgG2 prior to HTx were associated with a shorter survival post-HTx. Immunoglobulin deposition in cardiac tissue was significantly elevated in patients with a survival of less than 3 years. Patients with high plasma IgG levels pre-HTx also had significantly higher plasma levels after HTx. Furthermore, high pre-HTX levels of IgG1 and IgG2 levels were also significantly increased in patients with inflammatory infiltrate in CAV lesions. Altogether the results of this proof-of-concept study suggest that an activated immune response prior to transplantation negatively affects graft survival.
