{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T04:46:49Z","timestamp":1760244409034,"version":"build-2065373602"},"reference-count":46,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2022,12,30]],"date-time":"2022-12-30T00:00:00Z","timestamp":1672358400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Netherlands CardioVascular Research Initiative (CVON) of the Dutch Heart Foundation","award":["1161002016","725229"],"award-info":[{"award-number":["1161002016","725229"]}]},{"DOI":"10.13039\/501100001826","name":"ZonMW Translational Adult Stem Cell","doi-asserted-by":"publisher","award":["1161002016","725229"],"award-info":[{"award-number":["1161002016","725229"]}],"id":[{"id":"10.13039\/501100001826","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Dutch PLN foundation","award":["1161002016","725229"],"award-info":[{"award-number":["1161002016","725229"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/biology12010061","type":"journal-article","created":{"date-parts":[[2022,12,30]],"date-time":"2022-12-30T03:26:11Z","timestamp":1672370771000},"page":"61","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Elevated Plasma Immunoglobulin Levels Prior to Heart Transplantation Are Associated with Poor Post-Transplantation Survival"],"prefix":"10.3390","volume":"12","author":[{"given":"Patricia","family":"van den Hoogen","sequence":"first","affiliation":[{"name":"Laboratory for Experimental Cardiology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands"},{"name":"Circulatory Health Laboratory, Regenerative Medicine Center, Utrecht University, 3584 CX Utrecht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manon M. H.","family":"Huibers","sequence":"additional","affiliation":[{"name":"Department of Pathology, Circulatory Health Laboratory, University Medical Center Utrecht, Utrecht University, 3584 CX Utrecht, The Netherlands"},{"name":"Department of Genetics, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Floor W.","family":"van den Dolder","sequence":"additional","affiliation":[{"name":"Department of Pathology, Circulatory Health Laboratory, University Medical Center Utrecht, Utrecht University, 3584 CX Utrecht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roel","family":"de Weger","sequence":"additional","affiliation":[{"name":"Department of Pathology, Circulatory Health Laboratory, University Medical Center Utrecht, Utrecht University, 3584 CX Utrecht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erica","family":"Siera-de Koning","sequence":"additional","affiliation":[{"name":"Department of Pathology, Circulatory Health Laboratory, University Medical Center Utrecht, Utrecht University, 3584 CX Utrecht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3166-518X","authenticated-orcid":false,"given":"Marish I. F.","family":"Oerlemans","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicolaas","family":"de Jonge","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linda W.","family":"van Laake","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6257-7169","authenticated-orcid":false,"given":"Pieter A.","family":"Doevendans","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands"},{"name":"Netherlands Heart Institute (NLHI), 3511 EP Utrecht, The Netherlands"},{"name":"Centraal Militair Hospitaal (CMH), 3584 EZ Utrecht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2088-9102","authenticated-orcid":false,"given":"Joost. P. G.","family":"Sluijter","sequence":"additional","affiliation":[{"name":"Laboratory for Experimental Cardiology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands"},{"name":"Circulatory Health Laboratory, Regenerative Medicine Center, Utrecht University, 3584 CX Utrecht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9371-8788","authenticated-orcid":false,"given":"Aryan","family":"Vink","sequence":"additional","affiliation":[{"name":"Department of Pathology, Circulatory Health Laboratory, University Medical Center Utrecht, Utrecht University, 3584 CX Utrecht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5233-0066","authenticated-orcid":false,"given":"Saskia C. A.","family":"de Jager","sequence":"additional","affiliation":[{"name":"Laboratory for Experimental Cardiology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands"},{"name":"Circulatory Health Laboratory, Regenerative Medicine Center, Utrecht University, 3584 CX Utrecht, The Netherlands"},{"name":"Laboratory of Translational Immunology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2129","DOI":"10.1093\/eurheartj\/ehw128","article-title":"2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC)Developed with the special contribution of the Heart Failure Association (HFA) of the ESC","volume":"37","author":"Ponikowski","year":"2016","journal-title":"Eur. Heart J."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"7","DOI":"10.15420\/cfr.2016:25:2","article-title":"Global Public Health Burden of Heart Failure","volume":"3","author":"Savarese","year":"2017","journal-title":"Card. Fail. Rev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"3","DOI":"10.21037\/acs.2017.09.18","article-title":"Heart transplantation versus left ventricular assist devices as destination therapy or bridge to transplantation for 1-year mortality: A systematic review and meta-analysis","volume":"7","author":"Theochari","year":"2018","journal-title":"Ann. Cardiothorac. Surg."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1016\/j.healun.2017.07.019","article-title":"The Registry of the International Society for Heart and Lung Transplantation: Thirty-fourth Adult Heart Transplantation Report-2017; Focus Theme: Allograft ischemic time","volume":"36","author":"Lund","year":"2017","journal-title":"J. Heart Lung Transplant."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.1016\/j.healun.2017.07.016","article-title":"The Registry of the International Society for Heart and Lung Transplantation: Thirty-fourth Adult Lung And Heart-Lung Transplantation Report-2017; Focus Theme: Allograft ischemic time","volume":"36","author":"Chambers","year":"2017","journal-title":"J. Heart Lung Transplant."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1016\/j.healun.2018.07.022","article-title":"The International Thoracic Organ Transplant Registry of the International Society for Heart and Lung Transplantation: Thirty-fifth Adult Heart Transplantation Report-2018; Focus Theme: Multiorgan Transplantation","volume":"37","author":"Khush","year":"2018","journal-title":"J. Heart Lung Transplant."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.trim.2011.07.001","article-title":"Intimal fibrosis in human cardiac allograft vasculopathy","volume":"25","author":"Huibers","year":"2011","journal-title":"Transpl. Immunol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"562","DOI":"10.3325\/cmj.2014.55.562","article-title":"Cardiac allograft vasculopathy: Diagnosis, therapy, and prognosis","volume":"55","author":"Skoric","year":"2014","journal-title":"Croat. Med. J."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/j.atherosclerosis.2014.07.016","article-title":"Distinct phenotypes of cardiac allograft vasculopathy after heart transplantation: A histopathological study","volume":"236","author":"Huibers","year":"2014","journal-title":"Atherosclerosis"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1016\/j.healun.2014.11.022","article-title":"The composition of ectopic lymphoid structures suggests involvement of a local immune response in cardiac allograft vasculopathy","volume":"34","author":"Huibers","year":"2015","journal-title":"J. Heart Lung Transplant."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/j.trre.2018.05.002","article-title":"The clinical impact of donor-specific antibodies in heart transplantation","volume":"32","author":"Barten","year":"2018","journal-title":"Transplant. Rev."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1097\/MOT.0000000000000641","article-title":"The meaning of donor-specific antibodies after heart transplant","volume":"24","author":"Barten","year":"2019","journal-title":"Curr. Opin. Organ. Transplant."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"886","DOI":"10.1097\/00007890-200104150-00011","article-title":"Antivimentin antibodies are an independent predictor of transplant-associated coronary artery disease after cardiac transplantation","volume":"71","author":"Jurcevic","year":"2001","journal-title":"Transplantation"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1093\/icvts\/ivv344","article-title":"The impact of angiotensin II type 1 receptor antibodies on post-heart transplantation outcome in Heart Mate II bridged recipients","volume":"22","author":"Urban","year":"2016","journal-title":"Interact. Cardiovasc. Thorac. Surg."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1277","DOI":"10.1016\/j.healun.2010.05.025","article-title":"Characterization of immune responses to cardiac self-antigens myosin and vimentin in human cardiac allograft recipients with antibody-mediated rejection and cardiac allograft vasculopathy","volume":"29","author":"Nath","year":"2010","journal-title":"J. Heart Lung Transplant."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.trim.2013.10.007","article-title":"The impact of non-HLA antibodies directed against endothelin-1 type A receptors (ETAR) on early renal transplant outcomes","volume":"30","author":"Banasik","year":"2014","journal-title":"Transpl. Immunol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"702186","DOI":"10.3389\/fimmu.2021.702186","article-title":"Current Desensitization Strategies in Heart Transplantation","volume":"12","author":"Habal","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Civieri, G., Iop, L., and Tona, F. (2022). Antibodies against Angiotensin II Type 1 and Endothelin 1 Type A Receptors in Cardiovascular Pathologies. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23020927"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1111\/ajt.15564","article-title":"Hyperacute graft dysfunction in an orthotopic heart transplant in the presence of non-HLA antibodies","volume":"20","author":"Villa","year":"2020","journal-title":"Am. J. Transplant."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1016\/j.humimm.2020.09.003","article-title":"Association of vimentin antibody and other non-HLA antibodies with treated antibody mediated rejection in heart transplant recipients","volume":"81","author":"Zhang","year":"2020","journal-title":"Hum. Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1093\/eurheartj\/eht506","article-title":"High proportion of patients with end-stage heart failure regardless of aetiology demonstrates anti-cardiac antibody deposition in failing myocardium: Humoral activation, a potential contributor of disease progression","volume":"35","author":"Youker","year":"2014","journal-title":"Eur. Heart J."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"7505","DOI":"10.1111\/jcmm.14619","article-title":"Increased circulating IgG levels, myocardial immune cells and IgG deposits support a role for an immune response in pre- and end-stage heart failure","volume":"23","author":"Huibers","year":"2019","journal-title":"J. Cell. Mol. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e553","DOI":"10.1161\/CIR.0000000000000598","article-title":"Sensitization in Heart Transplantation: Emerging Knowledge: A Scientific Statement From the American Heart Association","volume":"139","author":"Colvin","year":"2019","journal-title":"Circulation"},{"key":"ref_24","first-page":"876","article-title":"Platelet transfusions are associated with the development of anti-major histocompatibility complex class I antibodies in patients with left ventricular assist support","volume":"17","author":"Moazami","year":"1998","journal-title":"J. Heart Lung Transplant."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1120","DOI":"10.1016\/S0003-4975(97)00807-2","article-title":"Factors influencing HLA sensitization in implantable LVAD recipients","volume":"64","author":"Massad","year":"1997","journal-title":"Ann. Thorac. Surg."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1016\/j.healun.2015.12.023","article-title":"Influence of durable mechanical circulatory support and allosensitization on mortality after heart transplantation","volume":"35","author":"Chiu","year":"2016","journal-title":"J. Heart Lung Transplant."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"838","DOI":"10.1016\/j.healun.2009.04.031","article-title":"Prior human leukocyte antigen-allosensitization and left ventricular assist device type affect degree of post-implantation human leukocyte antigen-allosensitization","volume":"28","author":"Drakos","year":"2009","journal-title":"J. Heart Lung Transplant."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1136\/bmj.2.5402.177","article-title":"Human Experimentation. Code of Ethics of the World Medical Association. Declaration of Helsinki","volume":"2","author":"Rickham","year":"1964","journal-title":"Br. Med. J."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1007\/s12471-019-1288-4","article-title":"UNRAVEL: Big data analytics research data platform to improve care of patients with cardiomyopathies using routine electronic health records and standardised biobanking","volume":"27","author":"Sammani","year":"2019","journal-title":"Neth. Heart J."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Gho, J.M., van Es, R., Stathonikos, N., Harakalova, M., te Rijdt, W.P., Suurmeijer, A.J., van der Heijden, J.F., de Jonge, N., Chamuleau, S.A., and de Weger, R.A. (2014). High resolution systematic digital histological quantification of cardiac fibrosis and adipose tissue in phospholamban p.Arg14del mutation associated cardiomyopathy. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0094820"},{"key":"ref_31","first-page":"S38","article-title":"Histopathology of graft coronary disease","volume":"11","author":"Billingham","year":"1992","journal-title":"J. Heart Lung Transplant."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1111\/ajt.13969","article-title":"Donor-Specific Antibodies Are Produced Locally in Ectopic Lymphoid Structures in Cardiac Allografts","volume":"17","author":"Huibers","year":"2017","journal-title":"Am. J. Transplant."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1324","DOI":"10.1016\/j.jacc.2020.01.014","article-title":"Inflammation in Heart Failure: JACC State-of-the-Art Review","volume":"75","author":"Murphy","year":"2020","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2055","DOI":"10.1161\/01.CIR.103.16.2055","article-title":"Cytokines and cytokine receptors in advanced heart failure: An analysis of the cytokine database from the Vesnarinone trial (VEST)","volume":"103","author":"Deswal","year":"2001","journal-title":"Circulation"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"15","DOI":"10.14797\/mdcj-9-1-15","article-title":"The role of B-cells in heart failure","volume":"9","author":"Youker","year":"2013","journal-title":"Methodist Debakey Cardiovasc. J."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"109828","DOI":"10.1016\/j.cellsig.2020.109828","article-title":"Adding insult to injury\u2014Inflammation at the heart of cardiac fibrosis","volume":"77","author":"Smolgovsky","year":"2021","journal-title":"Cell. Signal."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1007\/s11897-017-0337-9","article-title":"Inflammation\u2014Cause or Consequence of Heart Failure or Both?","volume":"14","author":"Tschope","year":"2017","journal-title":"Curr. Heart Fail. Rep."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Labarrere, C.A., Woods, J.R., Hardin, J.W., Jaeger, B.R., Zembala, M., Deng, M.C., and Kassab, G.S. (2014). Early inflammatory markers are independent predictors of cardiac allograft vasculopathy in heart-transplant recipients. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0113260"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1007\/s10741-018-9691-2","article-title":"Induction immunosuppressive therapy in cardiac transplantation: A systematic review and meta-analysis","volume":"23","author":"Briasoulis","year":"2018","journal-title":"Heart Fail. Rev."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1016\/j.healun.2016.10.004","article-title":"Evaluation of humoral immunity profiles to identify heart recipients at risk for development of severe infections: A multicenter prospective study","volume":"36","author":"Sarmiento","year":"2017","journal-title":"J. Heart Lung Transplant."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"4046","DOI":"10.1016\/j.transproceed.2005.09.153","article-title":"Decreased levels of serum immunoglobulins as a risk factor for infection after heart transplantation","volume":"37","author":"Sarmiento","year":"2005","journal-title":"Transplant. Proc."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"e12886","DOI":"10.1111\/eci.12886","article-title":"Soluble ST2 in end-stage heart failure, before and after support with a left ventricular assist device","volume":"48","author":"Tseng","year":"2018","journal-title":"Eur. J. Clin. Investig."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1626","DOI":"10.1016\/j.amjcard.2005.12.056","article-title":"Dynamic expression of the membrane attack complex (MAC) of the complement system in failing human myocardium","volume":"97","author":"Oliveira","year":"2006","journal-title":"Am. J. Cardiol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.carpath.2014.08.002","article-title":"Caspase-1 transcripts in failing human heart after mechanical unloading","volume":"24","author":"Prescimone","year":"2015","journal-title":"Cardiovasc. Pathol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1249","DOI":"10.1093\/eurjhf\/hfs120","article-title":"Circulating growth differentiation factor-15 correlates with myocardial fibrosis in patients with non-ischaemic dilated cardiomyopathy and decreases rapidly after left ventricular assist device support","volume":"14","author":"Lok","year":"2012","journal-title":"Eur. J. Heart Fail."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1164\/rccm.200510-1609OC","article-title":"Immunoglobulin G levels before and after lung transplantation","volume":"173","author":"Yip","year":"2006","journal-title":"Am. J. Respir. Crit. Care Med."}],"container-title":["Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-7737\/12\/1\/61\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:55:58Z","timestamp":1760147758000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-7737\/12\/1\/61"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,30]]},"references-count":46,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,1]]}},"alternative-id":["biology12010061"],"URL":"https:\/\/doi.org\/10.3390\/biology12010061","relation":{},"ISSN":["2079-7737"],"issn-type":[{"type":"electronic","value":"2079-7737"}],"subject":[],"published":{"date-parts":[[2022,12,30]]}}}