{"id":{"repo_id":"bielefeld","oai_identifier":"oai:pub.uni-bielefeld.de:2991795"},"canonical_url":"https://search.dev.ndltd.org/etd/bielefeld/oai:pub.uni-bielefeld.de:2991795","repository":{"repo_id":"bielefeld","name":"Universität Bielefeld","base_url":"https://pub.uni-bielefeld.de/oai"},"display":{"title":"Plasmatische und zelluläre, nicht invasive Biomarker für die Diagnostik kardialer Abstoßungsreaktionen","abstract":"The search for effective non-invasive biomarkers for rejection after organ transplantation has occupied research for many years. Invasive biopsies are still the only way to detect rejection after heart transplantation beyond doubt. Therefore, the focus of the present work was on potential plasmatic and cellular non-invasive biomarkers for cardiac rejection. Analysis of donor-specific cell-free DNA showed a significant correlation between elevated levels and the presence of cardiac rejection and its severity. Furthermore, for the first time, an association between increased levels of donor-specific cell-free DNA and the presence of pericardial effusions was demonstrated. This underlines the importance of evaluating non-invasive biomarkers also against the background of potential confounding factors. In case of markers of coagulation activation, D-dimers in particular were significantly elevated in a period of 9 – 30 days before validated rejection. This indicates D-dimers as possible early markers of cardiac rejection. The search for protein markers in cardioplegia solutions revealed that increased activation of the complement system may occur in the context of primary graft failure. This assumption is supported by an increased presence of the acute-phase protein CRP. Platelets in connection with complement C3 were considered as a possible cellular biomarker. It was shown that C3 is present in platelets and is released as a result of various stimuli. It was also shown that platelets can be activated by the anaphylatoxin C3a. These points show the essential role of platelets in the context of immune reactions, since they provide indications for a local increase in the C3 concentration due to platelet activation. Furthermore, a hitherto undescribed complex of C3 with Rab32 could be detected, which may play a role in the defense against cyto-invasive pathogens.<br /> The non-invasive diagnosis of cardiac rejection remains a challenge. It is becoming increasingly clear that a single biomarker alone will not be sufficient for specific and sensitive diagnostics. The development of suitable algorithms or scores that consider several non-invasive biomarkers will therefore move into focus in the future.","abstract_html":"The search for effective non-invasive biomarkers for rejection after organ transplantation has occupied research for many years. Invasive biopsies are still the only way to detect rejection after heart transplantation beyond doubt. Therefore, the focus of the present work was on potential plasmatic and cellular non-invasive biomarkers for cardiac rejection. Analysis of donor-specific cell-free DNA showed a significant correlation between elevated levels and the presence of cardiac rejection and its severity. Furthermore, for the first time, an association between increased levels of donor-specific cell-free DNA and the presence of pericardial effusions was demonstrated. This underlines the importance of evaluating non-invasive biomarkers also against the background of potential confounding factors. In case of markers of coagulation activation, D-dimers in particular were significantly elevated in a period of 9 – 30 days before validated rejection. This indicates D-dimers as possible early markers of cardiac rejection. The search for protein markers in cardioplegia solutions revealed that increased activation of the complement system may occur in the context of primary graft failure. This assumption is supported by an increased presence of the acute-phase protein CRP. Platelets in connection with complement C3 were considered as a possible cellular biomarker. It was shown that C3 is present in platelets and is released as a result of various stimuli. It was also shown that platelets can be activated by the anaphylatoxin C3a. These points show the essential role of platelets in the context of immune reactions, since they provide indications for a local increase in the C3 concentration due to platelet activation. Furthermore, a hitherto undescribed complex of C3 with Rab32 could be detected, which may play a role in the defense against cyto-invasive pathogens.&lt;br /&gt; The non-invasive diagnosis of cardiac rejection remains a challenge. It is becoming increasingly clear that a single biomarker alone will not be sufficient for specific and sensitive diagnostics. The development of suitable algorithms or scores that consider several non-invasive biomarkers will therefore move into focus in the future.","abstract_has_math":false,"creators":["Knüttgen, Franziska"],"institution":"Universität Bielefeld","degree_name":null,"degree_level":"thesis.doctoral","degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2024,"date_issued":"2024-06-06","date_published":"2024-06-06","updated_at":"2026-07-27T18:50:01Z","subjects":[],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://pub.uni-bielefeld.de/record/2991795","outbound_label":"Repository record","outbound_source":"source_url"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:creator","label":"Author","values":["Knüttgen, Franziska"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:publisher","label":"Institution","values":["Universitätsbibliothek Bielefeld"]},{"key":"dc:type","label":"Dc Type","values":["doctoralThesis"]},{"key":"thesis:degree_level","label":"Degree Level","values":["thesis.doctoral"]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["Universität Bielefeld"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["The search for effective non-invasive biomarkers for rejection after organ transplantation has occupied research for many years. Invasive biopsies are still the only way to detect rejection after heart transplantation beyond doubt. Therefore, the focus of the present work was on potential plasmatic and cellular non-invasive biomarkers for cardiac rejection. Analysis of donor-specific cell-free DNA showed a significant correlation between elevated levels and the presence of cardiac rejection and its severity. Furthermore, for the first time, an association between increased levels of donor-specific cell-free DNA and the presence of pericardial effusions was demonstrated. This underlines the importance of evaluating non-invasive biomarkers also against the background of potential confounding factors. In case of markers of coagulation activation, D-dimers in particular were significantly elevated in a period of 9 – 30 days before validated rejection. This indicates D-dimers as possible early markers of cardiac rejection. The search for protein markers in cardioplegia solutions revealed that increased activation of the complement system may occur in the context of primary graft failure. This assumption is supported by an increased presence of the acute-phase protein CRP. Platelets in connection with complement C3 were considered as a possible cellular biomarker. It was shown that C3 is present in platelets and is released as a result of various stimuli. It was also shown that platelets can be activated by the anaphylatoxin C3a. These points show the essential role of platelets in the context of immune reactions, since they provide indications for a local increase in the C3 concentration due to platelet activation. Furthermore, a hitherto undescribed complex of C3 with Rab32 could be detected, which may play a role in the defense against cyto-invasive pathogens.<br /> The non-invasive diagnosis of cardiac rejection remains a challenge. It is becoming increasingly clear that a single biomarker alone will not be sufficient for specific and sensitive diagnostics. The development of suitable algorithms or scores that consider several non-invasive biomarkers will therefore move into focus in the future."]},{"key":"dc:format.medium","label":"Dc Format Medium","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Plasmatische und zelluläre, nicht invasive Biomarker für die Diagnostik kardialer Abstoßungsreaktionen"]}]}],"canonical_facts":{"dc:creator":["Knüttgen, Franziska"],"dc:description.abstract":["The search for effective non-invasive biomarkers for rejection after organ transplantation has occupied research for many years. Invasive biopsies are still the only way to detect rejection after heart transplantation beyond doubt. Therefore, the focus of the present work was on potential plasmatic and cellular non-invasive biomarkers for cardiac rejection. Analysis of donor-specific cell-free DNA showed a significant correlation between elevated levels and the presence of cardiac rejection and its severity. Furthermore, for the first time, an association between increased levels of donor-specific cell-free DNA and the presence of pericardial effusions was demonstrated. This underlines the importance of evaluating non-invasive biomarkers also against the background of potential confounding factors. In case of markers of coagulation activation, D-dimers in particular were significantly elevated in a period of 9 – 30 days before validated rejection. This indicates D-dimers as possible early markers of cardiac rejection. The search for protein markers in cardioplegia solutions revealed that increased activation of the complement system may occur in the context of primary graft failure. This assumption is supported by an increased presence of the acute-phase protein CRP. Platelets in connection with complement C3 were considered as a possible cellular biomarker. It was shown that C3 is present in platelets and is released as a result of various stimuli. It was also shown that platelets can be activated by the anaphylatoxin C3a. These points show the essential role of platelets in the context of immune reactions, since they provide indications for a local increase in the C3 concentration due to platelet activation. Furthermore, a hitherto undescribed complex of C3 with Rab32 could be detected, which may play a role in the defense against cyto-invasive pathogens.<br /> The non-invasive diagnosis of cardiac rejection remains a challenge. It is becoming increasingly clear that a single biomarker alone will not be sufficient for specific and sensitive diagnostics. The development of suitable algorithms or scores that consider several non-invasive biomarkers will therefore move into focus in the future."],"dc:format.medium":["application/pdf"],"dc:publisher":["Universitätsbibliothek Bielefeld"],"dc:title":["Plasmatische und zelluläre, nicht invasive Biomarker für die Diagnostik kardialer Abstoßungsreaktionen"],"dc:type":["doctoralThesis"],"thesis:degree_level":["thesis.doctoral"],"thesis:institution_name":["Universität Bielefeld"]},"updated_at":"2026-07-27T18:50:01Z"}