TY - JOUR
T1 - Elevated Plasma Immunoglobulin Levels Prior to Heart Transplantation Are Associated with Poor Post-Transplantation Survival
AU - van den Hoogen, Patricia
AU - Huibers, Manon M.H.
AU - van den Dolder, Floor W.
AU - de Weger, Roel
AU - Siera-de Koning, Erica
AU - Oerlemans, Marish I.F.
AU - de Jonge, Nicolaas
AU - van Laake, Linda W.
AU - Doevendans, Pieter A.
AU - Sluijter, Joost P.G.
AU - Vink, Aryan
AU - de Jager, Saskia C.A.
N1 - Funding Information:
This work was supported by The Netherlands CardioVascular Research Initiative (CVON) of the Dutch Heart Foundation, Dutch Federation of University Medical Centers, the Netherlands Organization for Health Research and Development and, the Royal Netherlands Academy of Science (CVON HUSTCARE), a ZonMW Translational Adult Stem Cell grant (1161002016), a grant of the Dutch PLN foundation and by Horizon2020 ERC-2016-COG EVICARE (725229).
Publisher Copyright:
© 2022 by the authors.
PY - 2023/1
Y1 - 2023/1
N2 - 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.
AB - 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.
KW - cardiac allograft vasculopathy
KW - graft survival
KW - heart failure
KW - HTX
KW - immunoglobulin
KW - rejection
UR - http://www.scopus.com/inward/record.url?scp=85146744037&partnerID=8YFLogxK
U2 - 10.3390/biology12010061
DO - 10.3390/biology12010061
M3 - Article
AN - SCOPUS:85146744037
SN - 2079-7737
VL - 12
JO - Biology
JF - Biology
IS - 1
M1 - 61
ER -