149 results on '"Heidecke, Harald"'
Search Results
102. Antibodies Against GPCR
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Heidecke, Harald, primary
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- 2018
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103. Imbalanced levels of circulating autoantibodies targeting muscarinic acetylcholine receptors in patients with systemic lupus erythematosus and systemic sclerosis
- Author
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Sommerlatte, Sabine, Pitann, Silke, Rana, Mukaram, Marschner, Gabriele, Heidecke, Harald, Humrich, Jens, Lange, Tanja, Lamprecht, Peter, Müller, Antje, Cabral-Marques, Otavio, and Riemekasten, Gabriela
- Subjects
chronic fatigue syndrom ,systemic lupus erythematosus ,ddc: 610 ,autoantibodies ,systemic sclerosis ,muscarinic acetylcholine receptor ,610 Medical sciences ,Medicine - Abstract
Background: Muscarinic acetylcholine receptors belong to the family of G protein-coupled receptors and comprise several subtypes such as M1-M5. They are part of the parasympathetic nervous system but can also be found on non-neuronal cells including immune cells. It has become evident that autoantibodies[for full text, please go to the a.m. URL], 44. Kongress der Deutschen Gesellschaft für Rheumatologie (DGRh); 30. Jahrestagung der Deutschen Gesellschaft für Orthopädische Rheumatologie (DGORh); 26. Jahrestagung der Gesellschaft für Kinder- und Jugendrheumatologie (GKJR)
- Published
- 2016
104. Altered expression of C3a and C5a receptors in patients with rheumatic diseases
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Sommerlatte, Sabine, Pitann, Silke, Rana, Mukaram, Marschner, Gabriele, Heidecke, Harald, Humrich, Jens, Lamprecht, Peter, Müller, Antje, Cabral-Marques, Otavio, and Riemekasten, Gabriela
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rheumatoid arthritis ,C5a ,granulomatosis with polyangiitis ,systemic lupus erythematosus ,ddc: 610 ,systemic sclerosis ,610 Medical sciences ,Medicine ,C3a ,complement receptor - Abstract
Background: The complement system has multiple functions in the immune response such as the regulation of inflammatory mechanisms. Abnormalities of the complement system are known to play important roles in the pathogenesis of various rheumatic diseases. However, it remains to be determined if the expression[for full text, please go to the a.m. URL], 44. Kongress der Deutschen Gesellschaft für Rheumatologie (DGRh); 30. Jahrestagung der Deutschen Gesellschaft für Orthopädische Rheumatologie (DGORh); 26. Jahrestagung der Gesellschaft für Kinder- und Jugendrheumatologie (GKJR)
- Published
- 2016
105. Non-HLA Antibodies Impact on C4d Staining, Stellate Cell Activation and Fibrosis in Liver Allografts
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O'Leary, Jacqueline G., primary, Demetris, Anthony J., additional, Philippe, Aurélie, additional, Freeman, Robert, additional, Cai, Junchao, additional, Heidecke, Harald, additional, Smith, Cory, additional, Hart, Brent, additional, Jennings, Linda W., additional, Catar, Rusan, additional, Everly, Mathew, additional, Klintmalm, Goran B., additional, and Dragun, Duska, additional
- Published
- 2017
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106. Soluble (pro)renin receptor in preeclampsia and diabetic pregnancies
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Sugulle, Meryam, primary, Heidecke, Harald, additional, Maschke, Ulrike, additional, Herse, Florian, additional, Danser, A.H. Jan, additional, Mueller, Dominik N., additional, Staff, Anne Cathrine, additional, and Dechend, Ralf, additional
- Published
- 2017
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107. Antibodies to Signaling Molecules and Receptors in Alzheimer’s Disease are Associated with Psychomotor Slowing, Depression, and Poor Visuospatial Function
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Giil, Lasse M., primary, Vedeler, Christian A., additional, Kristoffersen, Einar K., additional, Nordrehaug, Jan Erik, additional, Heidecke, Harald, additional, Dechend, Ralf, additional, Schulze-Forster, Kai, additional, Muller, Dominik N., additional, von Goetze, Victoria S., additional, Cabral-Marques, Otavio, additional, Riemekasten, Gabriela, additional, Vogelsang, Petra, additional, Nygaard, Staale, additional, Lund, Anders, additional, and Aarsland, Dag, additional
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- 2017
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108. Anti-AT1R and anti-ETAR autoantibodies from patients with SSc and their agonistic effects
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Kill, Angela, Tabeling, Christoph, Kühl, Anja A., Günther, Jeannine, Becker, Mike, Heidecke, Harald, Dragun, Duska, Burmester, Gerd-Rüdiger, and Riemekasten, Gabriela
- Subjects
integumentary system ,ddc: 610 ,autoantibodies ,sclerosis ,pathogenesis ,610 Medical sciences ,Medicine ,systemic ,angiotensin ,skin and connective tissue diseases ,endothelin - Abstract
Background: Agonistic autoantibodies to angiotensin II type 1 receptor (AT1R) and endothelin 1 type A receptor (ETAR) are found in elevated levels in systemic sclerosis (SSc). Furthermore, these autoantibodies show distinct associations to increased risk of SSc-related manifestations and reduced cumulative[for full text, please go to the a.m. URL], 42. Kongress der Deutschen Gesellschaft für Rheumatologie (DGRh); 28. Jahrestagung der Deutschen Gesellschaft für Orthopädische Rheumatologie (DGORh); 24. wissenschaftliche Jahrestagung der Gesellschaft für Kinder- und Jugendrheumatologie (GKJR)
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- 2014
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109. Y-box protein-1/p18 as novel serum marker for ovarian cancer diagnosis: A study by the Tumor Bank Ovarian Cancer (TOC)
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Rohr, Irena, primary, Braicu, Elena I., additional, En-Nia, Abdelaziz, additional, Heinrich, Michaela, additional, Richter, Rolf, additional, Chekerov, Radoslav, additional, Dechend, Ralf, additional, Heidecke, Harald, additional, Dragun, Duska, additional, Schäfer, Reinhold, additional, Gorny, Xenia, additional, Lindquist, Jonathan A., additional, Brandt, Sabine, additional, Sehouli, Jalid, additional, and Mertens, Peter R., additional
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- 2016
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110. Predictive and Prognostic Value of sPRR in Patients with Primary Epithelial Ovarian Cancer
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Kreienbring, Katrin, primary, Franz, Annika, additional, Richter, Rolf, additional, Dragun, Duska, additional, Heidecke, Harald, additional, Dechend, Ralf, additional, Muller, Dominik N., additional, Sehouli, Jalid, additional, and Braicu, Elena I., additional
- Published
- 2016
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111. P46. Dysregulated level of novel circulating autoantibodies in preeclampsia
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Moe, Kjartan, primary, Heidecke, Harald, additional, Dechend, Ralf, additional, and Staff, Anne Cathrine, additional
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- 2015
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112. Increase of angiotensin II type 1 receptor auto-antibodies in Huntington’s disease
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Lee, De-Hyung, primary, Heidecke, Harald, additional, Schröder, Alexandra, additional, Paul, Friedemann, additional, Wachter, Rolf, additional, Hoffmann, Rainer, additional, Ellrichmann, Gisa, additional, Dragun, Duska, additional, Waschbisch, Anne, additional, Stegbauer, Johannes, additional, Klotz, Peter, additional, Gold, Ralf, additional, Dechend, Ralf, additional, Müller, Dominik N, additional, Saft, Carsten, additional, and Linker, Ralf A, additional
- Published
- 2014
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113. OR51
- Author
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Taniguchi, Michiko, primary, Hidenori, Ohe, additional, Uemoto, Shinji, additional, Schulze-Forster, Kai, additional, Heidecke, Harald, additional, Dragun, Duska, additional, Riemekasten, Gabriela, additional, Dechend, Ralf, additional, Maehara, Curtis, additional, Hopfield, Judy, additional, and Terasaki, Paul I., additional
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- 2014
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114. Autoantibodies (AA) against the EGF/EGFR and VEGFA/VEGFR1 as prognosticator in epithelial ovarian cancer (EOC) patients.
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Braicu, Elena Ioana, primary, Dechend, Ralf, additional, Dragun, Duska, additional, Busjahn, Andreas, additional, Wachter, Rolf, additional, Riemekasten, Gabriela, additional, Golic, Michaela, additional, Heidecke, Harald, additional, Kuhberg, Marc, additional, Mueller, Dominik N, additional, and Sehouli, Jalid, additional
- Published
- 2014
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115. In arterial occlusive disease autoantibodies against ETAR and AT1R correlate with each other but are not associated with classical cardiovascular risk factors
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Albert, Christian, primary, Schultzendorff, Marie, additional, Şalaru, Delia, additional, Halloul, Zuhir, additional, Dragun, Duska, additional, Heidecke, Harald, additional, and Mertens, Peter R., additional
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- 2014
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116. Angiotensin receptor type 1 and endothelin receptor type A on immune cells mediate migration and the expression of IL-8 and CCL18 when stimulated by autoantibodies from systemic sclerosis patients
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Günther, Jeannine, primary, Kill, Angela, additional, Becker, Mike, additional, Heidecke, Harald, additional, Rademacher, Judith, additional, Siegert, Elise, additional, Radić, Mislav, additional, Burmester, Gerd-Rüdiger, additional, Dragun, Duska, additional, and Riemekasten, Gabriela, additional
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- 2014
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117. Autoantibodies to angiotensin and endothelin receptors in systemic sclerosis induce cellular and systemic events associated with disease pathogenesis
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Kill, Angela, primary, Tabeling, Christoph, additional, Undeutsch, Reinmar, additional, Kühl, Anja A, additional, Günther, Jeannine, additional, Radic, Mislav, additional, Becker, Mike O, additional, Heidecke, Harald, additional, Worm, Margitta, additional, Witzenrath, Martin, additional, Burmester, Gerd-Rüdiger, additional, Dragun, Duska, additional, and Riemekasten, Gabriela, additional
- Published
- 2014
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118. A10.2 Anti-AT1R and Anti-Etar Autoantibodies in Pathogenesis of Systemis Sclerosis
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Kill, Angela, primary, O Becker, Mike, additional, Guenther, Jeannine, additional, Heidecke, Harald, additional, Dragun, Duska, additional, and Riemekasten, Gabriela, additional
- Published
- 2013
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119. Non-HLA-antibodies targeting Angiotensin type 1 receptor and antibody mediated rejection
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Dragun, Duska, primary, Catar, Rusan, additional, Kusch, Angelika, additional, Heidecke, Harald, additional, and Philippe, Aurélie, additional
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- 2012
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120. Non-HLA Antibodies Targeting Vascular Receptors Enhance Alloimmune Response and Microvasculopathy After Heart Transplantation
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Hiemann, Nicola E., primary, Meyer, Rudolf, additional, Wellnhofer, Ernst, additional, Schoenemann, Constanze, additional, Heidecke, Harald, additional, Lachmann, Nils, additional, Hetzer, Roland, additional, and Dragun, Duska, additional
- Published
- 2012
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121. Angiotensin II Type 1 Receptor Antibodies and Increased Angiotensin II Sensitivity in Pregnant Rats
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Wenzel, Katrin, primary, Rajakumar, Augustine, additional, Haase, Hannelore, additional, Geusens, Nele, additional, Hubner, Norbert, additional, Schulz, Herbert, additional, Brewer, Justin, additional, Roberts, Lyndsay, additional, Hubel, Carl A., additional, Herse, Florian, additional, Hering, Lydia, additional, Qadri, Fatimunnisa, additional, Lindschau, Carsten, additional, Wallukat, Gerd, additional, Pijnenborg, Robert, additional, Heidecke, Harald, additional, Riemekasten, Gabriela, additional, Luft, Friedrich C., additional, Muller, Dominik N., additional, Lamarca, Babette, additional, and Dechend, Ralf, additional
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- 2011
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122. Anti-Angiotensin Type 1 Receptor Antibodies Associated With Antibody Mediated Rejection in Donor HLA Antibody Negative Patients
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Reinsmoen, Nancy L., primary, Lai, Chih-Hung, additional, Heidecke, Harald, additional, Haas, Mark, additional, Cao, Kai, additional, Ong, Geraldine, additional, Naim, Mehrnoush, additional, Wang, Qi, additional, Mirocha, James, additional, Kahwaji, Joseph, additional, Vo, Ashley A., additional, Jordan, Stanley C., additional, and Dragun, Duska, additional
- Published
- 2010
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123. Involvement of functional autoantibodies against vascular receptors in systemic sclerosis
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Riemekasten, Gabriela, primary, Philippe, Aurélie, additional, Näther, Melanie, additional, Slowinski, Torsten, additional, Müller, Dominik N, additional, Heidecke, Harald, additional, Matucci-Cerinic, Marco, additional, Czirják, László, additional, Lukitsch, Ivo, additional, Becker, Mike, additional, Kill, Angela, additional, van Laar, Jacob M, additional, Catar, Rusan, additional, Luft, Friedrich C, additional, Burmester, Gerd R, additional, Hegner, Björn, additional, and Dragun, Duska, additional
- Published
- 2010
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124. 170-P: Angiotensin II Type 1 Receptor Antibodies in a Case of Hyperacute Renal Allograft Rejection
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Lunz, John G., primary, Shapiro, Ron, additional, Randawa, Parmjeet, additional, Heidecke, Harald, additional, Dragun, Duska, additional, and Zeevi, Adriana, additional
- Published
- 2010
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125. α1A-Adrenergic Receptor-Directed Autoimmunity Induces Left Ventricular Damage and Diastolic Dysfunction in Rats
- Author
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Wenzel, Katrin, primary, Wallukat, Gerd, additional, Qadri, Fatimunnisa, additional, Hubner, Norbert, additional, Schulz, Herbert, additional, Hummel, Oliver, additional, Herse, Florian, additional, Heuser, Arnd, additional, Fischer, Robert, additional, Heidecke, Harald, additional, Luft, Friedrich C., additional, Muller, Dominik N., additional, Dietz, Rainer, additional, and Dechend, Ralf, additional
- Published
- 2010
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126. Vitronectin Concentrations Predict Risk in Patients Undergoing Coronary Stenting
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Derer, Wolfgang, primary, Barnathan, Elliot S., additional, Safak, Erdal, additional, Agarwal, Prasheen, additional, Heidecke, Harald, additional, Möckel, Martin, additional, Gross, Michael, additional, Oezcelik, Cemil, additional, Dietz, Rainer, additional, and Dechend, Ralf, additional
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- 2009
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127. Increase of angiotensin II type 1 receptor auto-antibodies in Huntington's disease.
- Author
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Waschbisch, Anne, De-Hyung Lee, Linker, Ralf A., Schröder, Alexandra, Hoffmann, Rainer, Ellrichmann, Gisa, Klotz, Peter, Gold, Ralf, Saft, Carsten, Heidecke, Harald, Paul, Friedemann, Wachter, Rolf, Dragun, Duska, Stegbauer, Johannes, Müller, Dominik N., and Dechend, Ralf
- Subjects
ANGIOTENSIN receptors ,HUNTINGTON disease ,MULTIPLE sclerosis ,NEURODEGENERATION ,IMMUNE system ,PHYSIOLOGY - Abstract
Background In the recent years, a role of the immune system in Huntington's disease (HD) is increasingly recognized. Here we investigate the presence of T cell activating auto-antibodies against angiotensin II type 1 receptors (AT1R) in all stages of the disease as compared to healthy controls and patients suffering from multiple sclerosis (MS) as a prototype neurologic autoimmune disease. Results As compared to controls, MS patients show higher titers of anti-AT1R antibodies, especially in individuals with active disease. In HD, anti-AT1R antibodies are more frequent than in healthy controls or even MS and occur in 37.9% of patients with relevant titers ≥ 20 U/ml. In a correlation analysis with clinical parameters, the presence of AT1R antibodies in the sera of HD individuals inversely correlated with the age of onset and positively with the disease burden score as well as with smoking and infection. Conclusions These data suggest a dysfunction of the adaptive immune system in HD which may be triggered by different stimuli including autoimmune responses, infection and possibly also smoking. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
128. Immunosuppressive Treatment Protects Against Angiotensin II-Induced Renal Damage
- Author
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Muller, Dominik N., primary, Shagdarsuren, Erdenechimeg, additional, Park, Joon-Keun, additional, Dechend, Ralf, additional, Mervaala, Eero, additional, Hampich, Franziska, additional, Fiebeler, Anette, additional, Ju, Xinsheng, additional, Finckenberg, Piet, additional, Theuer, Jürgen, additional, Viedt, Christiane, additional, Kreuzer, Joerg, additional, Heidecke, Harald, additional, Haller, Hermann, additional, Zenke, Martin, additional, and Luft, Friedrich C., additional
- Published
- 2002
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129. Prothymosin αl effects in vitro on chemotaxis, cytotoxicity and oxidative response of neutrophils from melanoma, colorectal and breast tumor patients
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Heidecke, Harald, primary, Eckert, Klaus, additional, Schulze-Forster, Kai, additional, and Maurer, H.Rainer, additional
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- 1997
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130. α1A-Adrenergic Receptor-Directed Autoimmunity Induces Left Ventricular Damage and Diastolic Dysfunction in Rats.
- Author
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Wenzel, Katrin, Wallukat, Gerd, Qadri, Fatimunnisa, Hubner, Norbert, Schulz, Herbert, Hummel, Oliver, Herse, Florian, Heuser, Arnd, Fischer, Robert, Heidecke, Harald, Luft, Friedrich C., Muller, Dominik N., Dietz, Rainer, and Dechend, Ralf
- Subjects
AUTOANTIBODIES ,HYPERTENSION ,RATS ,ADRENERGIC receptors ,BLOOD pressure measurement ,PHOSPHORYLATION ,IMMUNIZATION ,ANGIOTENSINS ,HEART fibrosis - Abstract
Background: Agonistic autoantibodies to the α
1 -adrenergic receptor occur in nearly half of patients with refractory hypertension; however, their relevance is uncertain. Methods/Principal Findings: We immunized Lewis rats with the second extracellular-loop peptides of the human α1A -adrenergic receptor and maintained them for one year. α1A -adrenergic antibodies (α1A -AR-AB) were monitored with a neonatal cardiomyocyte contraction assay by ELISA, and by ERK1/2 phosphorylation in human α1A -adrenergic receptor transfected Chinese hamster ovary cells. The rats were followed with radiotelemetric blood pressure measurements and echocardiography. At 12 months, the left ventricles of immunized rats had greater wall thickness than control rats. The fractional shortening and dp/dtmax demonstrated preserved systolic function. A decreased E/A ratio in immunized rats indicated a diastolic dysfunction. Invasive hemodynamics revealed increased left ventricular end-diastolic pressures and decreased dp/dtmin . Mean diameter of cardiomyocytes showed hypertrophy in immunized rats. Long-term blood pressure values and heart rates were not different. Genes encoding sarcomeric proteins, collagens, extracellular matrix proteins, calcium regulating proteins, and proteins of energy metabolism in immunized rat hearts were upregulated, compared to controls. Furthermore, fibrosis was present in immunized hearts, but not in control hearts. A subset of immunized and control rats was infused with angiotensin (Ang) II. The stressor raised blood pressure to a greater degree and led to more cardiac fibrosis in immunized, than in control rats. Conclusions/Significance: We show that α1A -AR-AB cause diastolic dysfunction independent of hypertension, and can increase the sensitivity to Ang II. We suggest that α1A -AR-AB could contribute to cardiovascular endorgan damage. [ABSTRACT FROM AUTHOR]- Published
- 2010
- Full Text
- View/download PDF
131. Autoantibodies Targeting AT 1 - and ET A -Receptors Link Endothelial Proliferation and Coagulation via Ets-1 Transcription Factor.
- Author
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Catar, Rusan, Herse-Naether, Melanie, Zhu, Nan, Wagner, Philine, Wischnewski, Oskar, Kusch, Angelika, Kamhieh-Milz, Julian, Eisenreich, Andreas, Rauch, Ursula, Hegner, Björn, Heidecke, Harald, Kill, Angela, Riemekasten, Gabriela, Kleinau, Gunnar, Scheerer, Patrick, Dragun, Duska, and Philippe, Aurelie
- Subjects
TRANSCRIPTION factors ,MITOGEN-activated protein kinases ,G protein coupled receptors ,BLOOD coagulation ,PREPROENDOTHELIN ,FC receptors ,AUTOANTIBODIES ,BOTULINUM A toxins - Abstract
Scleroderma renal crisis (SRC) is an acute life-threatening manifestation of systemic sclerosis (SSc) caused by obliterative vasculopathy and thrombotic microangiopathy. Evidence suggests a pathogenic role of immunoglobulin G (IgG) targeting G-protein coupled receptors (GPCR). We therefore dissected SRC-associated vascular obliteration and investigated the specific effects of patient-derived IgG directed against angiotensin II type 1 (AT
1 R) and endothelin-1 type A receptors (ETA R) on downstream signaling events and endothelial cell proliferation. SRC-IgG triggered endothelial cell proliferation via activation of the mitogen-activated protein kinase (MAPK) pathway and subsequent activation of the E26 transformation-specific-1 transcription factor (Ets-1). Either AT1 R or ETA R receptor inhibitors/shRNA abrogated endothelial proliferation, confirming receptor activation and Ets-1 signaling involvement. Binding of Ets-1 to the tissue factor (TF) promoter exclusively induced TF. In addition, TF inhibition prevented endothelial cell proliferation. Thus, our data revealed a thus far unknown link between SRC-IgG-induced intracellular signaling, endothelial cell proliferation and active coagulation in the context of obliterative vasculopathy and SRC. Patients' autoantibodies and their molecular effectors represent new therapeutic targets to address severe vascular complications in SSc. [ABSTRACT FROM AUTHOR]- Published
- 2022
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- View/download PDF
132. Increase of angiotensin II type 1 receptor auto-antibodies in Huntington’s disease
- Author
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Lee, De-Hyung, Heidecke, Harald, Schröder, Alexandra, Paul, Friedemann, Wachter, Rolf, Hoffmann, Rainer, Ellrichmann, Gisa, Dragun, Duska, Waschbisch, Anne, Stegbauer, Johannes, Klotz, Peter, Gold, Ralf, Dechend, Ralf, Müller, Dominik N., Saft, Carsten, and Linker, Ralf A.
- Subjects
600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit ,3. Good health - Abstract
Background In the recent years, a role of the immune system in Huntington’s disease (HD) is increasingly recognized. Here we investigate the presence of T cell activating auto-antibodies against angiotensin II type 1 receptors (AT1R) in all stages of the disease as compared to healthy controls and patients suffering from multiple sclerosis (MS) as a prototype neurologic autoimmune disease. Results As compared to controls, MS patients show higher titers of anti-AT1R antibodies, especially in individuals with active disease. In HD, anti-AT1R antibodies are more frequent than in healthy controls or even MS and occur in 37.9% of patients with relevant titers ≥ 20 U/ml. In a correlation analysis with clinical parameters, the presence of AT1R antibodies in the sera of HD individuals inversely correlated with the age of onset and positively with the disease burden score as well as with smoking and infection. Conclusions These data suggest a dysfunction of the adaptive immune system in HD which may be triggered by different stimuli including autoimmune responses, infection and possibly also smoking.
133. Non-HLA Autoantibodies at 1 Year Negatively Affect 5-Year Native Renal Function in Liver Transplant Recipients.
- Author
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O'Leary, Jacqueline G., Philippe, Aurélie, Freeman, Robert, Heidecke, Harald, Jennings, Linda W., Catar, Rusan, Klintmalm, Goran B., and Dragun, Duska
- Subjects
- *
KIDNEY physiology , *LIVER transplantation , *AUTOANTIBODIES , *VASCULAR endothelial cells , *ANGIOTENSIN II - Abstract
Angiotensin II type-1 receptor (AT 1 R) and endothelin-1 type A receptor (ET A R) autoantibodies, in addition to allograft injury, can bind native endothelial cells and cause vascular vasoconstriction and fibrosis progression in nontransplanted organs. Therefore, we investigated long-term native renal function in liver transplant (LT) recipients with and without anti-AT 1 R-Abs and/or anti-ET A R-Abs present in serum. Primary LT recipients at our single center from January 2000 to April 2009 had their prospectively collected pre-LT (1269 patients) and year 1 post-LT (795 patients) serum tested retrospectively for anti-AT 1 R-Abs and/or anti-ET A R-Abs. Anti-AT 1 R-Abs and anti-ET A R-Abs testing was accomplished with a standardized solid phase assay in which >10 U was considered positive. Pretransplant anti-AT 1 R-Abs and/or anti-ET A R-Abs did not change the median delta creatinine from pretransplant to 1 year post-transplant. In multivariable analysis controlling for diabetes (DM) and calcineurin inhibitor (CNI) use, anti-AT 1 R-Abs and/or anti-ET A R-Abs at 1-year remained statistically significantly associated with a decline in GFR (measured by Modification of Diet in Renal Disease-6) from years 1-5 post-LT (P =.04). In diabetic patients the association with a decline in renal function was more pronounced with (-9.29 mL/min) vs without (-2.28 mL/min) anti-AT 1 R-Abs and/or anti-ET A R-Abs at year 1, respectively (P =.004). At 1-year post-LT, the autoantibodies anti-AT 1 R-Abs and/or anti-ET A R-Abs are associated in multivariable analysis with an increased risk of native renal function decline especially in diabetic patients. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
134. OR51: ANTIBODIES AGAINST PROTEASE-ACTIVATED RECEPTORS (PAR) AFTER IMMUNOSUPPRESSION WITHDRAWAL IN PEDIATRIC LIVING-DONOR LIVER TRANSPLANT.
- Author
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Taniguchi, Michiko, Hidenori, Ohe, Uemoto, Shinji, Schulze-Forster, Kai, Heidecke, Harald, Dragun, Duska, Riemekasten, Gabriela, Dechend, Ralf, Maehara, Curtis, Hopfield, Judy, and Terasaki, Paul I.
- Subjects
- *
IMMUNOGLOBULIN G , *HLA histocompatibility antigens , *SINGLE molecules , *LIVER transplantation , *ORGAN donors , *PEDIATRICS - Abstract
Aim While the importance of non-HLA antibodies’ (Abs) pathological role has been emerging in kidney transplantation, the involvement of non-HLA Abs after liver transplantation remains poorly understood. Our study explored the effect of Abs against PAR in pediatric living-donor liver transplant (LDLT) patients after immunosuppression withdrawal (ISW). PAR are G protein-coupled receptors (GPCR) activated by proteolysis; their involvement in inflammatory pathologies has been indicated. Methods The study enrolled 69 pediatric LDLT patients; 16 achieved operational tolerance, 53 experienced rejection and/or fibrosis (intolerance) after ISW. Post-ISW sera (10.7 ± 4 years post) were screened for antibodies against two different PAR isoforms (PAR1 and PAR2) and against other GPCR using ELISA (CellTrend, Germany). Results Levels of Abs against PAR2 – but not PAR1 or other GPCR – were significantly higher in the intolerance group than in those tolerating ISW ( P = 0.04). Further classification of the intolerance group showed that those who had rejection after ISW (median 2.2 years) had significantly higher levels of anti-PAR2 than those who developed fibrosis alone (median post-ISW 10.7 years) ( P = 0.03). Comparison of anti-GPCR and liver function test results showed that, in the whole population, only anti-PAR2 had significant correlation with aspartate aminotransferase ( R = 0.43, P < 0.001) and alanine aminotransferase ( R = 0.31, P = 0.01). And only anti-PAR2 showed significant association with C4d deposition. Conclusions This is the first report to show that the Abs against PAR2 were detectable distinctively in patients who had rejection after ISW. The significant correlation of clinical parameters with higher levels of anti-PAR2 (but not the other anti-GPCR) may indicate a pathological role of anti-PAR2 in liver damage. Thus, the current findings may suggest a new aspect of non-HLA Abs against GPCR in liver transplantation. This hypothesis awaits the next step of studying how and when anti-PAR2 are developed after ISW. K. Schulze-Forster: Other (Identify); Company/Organization; CellTrend GmbH (owner) . H. Heidecke: Other (Identify); Company/Organization; CellTrend GmbH (owner). [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
135. Angiotensin II Type 2 Receptor Antibodies in Glomerular Diseases.
- Author
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Szymczak M, Heidecke H, Żabińska M, Rukasz D, Wiśnicki K, Kujawa K, Kościelska-Kasprzak K, Krajewska M, and Banasik M
- Subjects
- Humans, Female, Male, Middle Aged, Adult, Aged, Kidney Glomerulus immunology, Kidney Glomerulus pathology, Glomerulonephritis, Membranous immunology, Glomerulonephritis, Membranous blood, Glomerulonephritis immunology, Glomerulonephritis blood, Antibodies, Antineutrophil Cytoplasmic immunology, Antibodies, Antineutrophil Cytoplasmic blood, Lupus Erythematosus, Systemic immunology, Lupus Erythematosus, Systemic blood, Glomerulonephritis, IGA immunology, Glomerulonephritis, IGA blood, Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis immunology, Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis blood, Lupus Nephritis immunology, Receptor, Angiotensin, Type 1 immunology, Young Adult, Kidney Diseases immunology, Receptor, Angiotensin, Type 2 immunology, Receptor, Angiotensin, Type 2 metabolism, Autoantibodies blood, Autoantibodies immunology
- Abstract
We evaluated the concentration of AT2R antibodies in 136 patients with primary and secondary glomerular diseases: membranous nephropathy (n = 18), focal and segmental glomerulosclerosis (n = 25), systemic lupus erythematosus (n = 17), immunoglobulin A (IgA) nephropathy (n = 14), mesangial (non-IgA) proliferative nephropathy (n = 6), c-ANCA vasculitis (n = 40), perinuclear anti-neutrophil cytoplasmic antibodies (p-ANCA) vasculitis (n = 16), and compared it with a healthy control group (22 patients). Serum creatinine levels, proteinuria, serum albumin, and total protein concentrations were prospectively recorded for 2 years. The mean levels of AT2R antibodies in the lupus nephropathy group were significantly higher compared to the control group, 64.12 ± 26.95 units/mL and 9.72 ± 11.88 units/mL, respectively. There was no association between this level and the clinical course of the disease. The AT2R levels in other kinds of glomerular disease were no different from the control group. We found significant correlations between AT1R and AT2R in patients with membranous nephropathy (r = 0.66), IgA nephropathy (r = 0.61), and c-ANCA vasculitis (r = 0.63). Levels of AT2R antibodies in systemic lupus erythematosus are higher compared to other types of glomerulonephritis, vasculitis, and a healthy control group. Levels of AT2R antibodies correlate with AT1R antibodies in the groups of patients with membranous nephropathy, IgA nephropathy, and c-ANCA vasculitis. These kinds of AT2R antibodies have a stimulative effect on AT2R, but we have not found the influence of these antibodies on the clinical course of glomerular diseases., (© 2024 Maciej Szymczak et al., published by Sciendo.)
- Published
- 2024
- Full Text
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136. Low avidity circulating SARS-CoV-2 reactive CD8+ T cells with proinflammatory TEMRA phenotype are associated with post-acute sequelae of COVID-19.
- Author
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Paniskaki K, Konik MJ, Anft M, Heidecke H, Meister TL, Pfaender S, Krawczyk A, Zettler M, Jäger J, Gaeckler A, Dolff S, Westhoff TH, Rohn H, Stervbo U, Scheibenbogen C, Witzke O, and Babel N
- Abstract
The role of adaptive SARS-CoV-2 specific immunity in post-acute sequelae of COVID-19 (PASC) is not well explored, although a growing population of convalescent COVID-19 patients with manifestation of PASC is observed. We analyzed the SARS-CoV-2-specific immune response, via pseudovirus neutralizing assay and multiparametric flow cytometry in 40 post-acute sequelae of COVID-19 patients with non-specific PASC manifestation and 15 COVID-19 convalescent healthy donors. Although frequencies of SARS-CoV-2-reactive CD4+ T cells were similar between the studied cohorts, a stronger SARS-CoV-2 reactive CD8+ T cell response, characterized by IFN γ production and predominant T
EMRA phenotype but low functional TCR avidity was detected in PASC patients compared to controls. Of interest, high avidity SARS-CoV-2-reactive CD4+ and CD8+ T cells were comparable between the groups demonstrating sufficient cellular antiviral response in PASC. In line with the cellular immunity, neutralizing capacity in PASC patients was not inferior compared to controls. In conclusion, our data suggest that PASC may be driven by an inflammatory response triggered by an expanded population of low avidity SARS-CoV-2 reactive pro-inflammatory CD8+ T cells. These pro-inflammatory T cells with TEMRA phenotype are known to be activated by a low or even without TCR stimulation and lead to a tissue damage. Further studies including animal models are required for a better understanding of underlying immunopathogensis. Summary: A CD8+ driven persistent inflammatory response triggered by SARS-CoV-2 may be responsible for the observed sequelae in PASC patients., Competing Interests: Author HH was employed by company CellTrend GmbH. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Paniskaki, Konik, Anft, Heidecke, Meister, Pfaender, Krawczyk, Zettler, Jäger, Gaeckler, Dolff, Westhoff, Rohn, Stervbo, Scheibenbogen, Witzke and Babel.)- Published
- 2023
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137. Possible Association Between Anti-Trisulfated-Heparin-Disaccharide (TS-HDS) Immunoglobulin M Autoantibody and Fibromyalgia Syndrome.
- Author
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Nissan J, Blokh A, Ben-Shabat N, Heidecke H, Halpert G, Shoenfeld Y, and Amital H
- Subjects
- Humans, Female, Autoantibodies, Cross-Sectional Studies, Immunoglobulin M metabolism, Disaccharides metabolism, Heparin, Fibromyalgia diagnosis, Fibromyalgia epidemiology
- Abstract
Background: Fibromyalgia syndrome (FMS) is estimated to affect 2-4% of the general population. While FMS has some known environmental and genetic risk factors, the disorder has no clear etiology. A common coexisting disorder with FMS is small fiber neuropathy (SFN). High levels of serum immunoglobulin M (IgM) binding to trisulfated-heparin-disaccharide (TS-HDS) were recently found to be associated with SFN., Objectives: To evaluate potential differences in anti-TS-HDS antibody titers in women with FMS compared to healthy controls., Methods: In this cross-sectional study, we evaluated 51 female participants: 30 with a diagnosis of FMS and 21 healthy controls who had been recruited at the Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Israel. All of the participants were older than 18 years of age. Anti-TS-HDS IgM levels were measured in their sera using the enzyme immunoassay technique., Results: The mean anti-TS-HDS IgM levels were significantly lower in the FMS group, compared with the control group (7.7 ± 5 vs. 13.2 ± 8.6 U/ml, respectively; P = 0.013)., Conclusions: There is a possible association between FMS and anti-TS-HDS IgM. This association might be the missing link for the coexistence of SFN and FMS, but further study should be performed to assess this association and this auto-antibody characteristic.
- Published
- 2023
138. Autoantibodies Targeting AT 1 - and ET A -Receptors Link Endothelial Proliferation and Coagulation via Ets-1 Transcription Factor.
- Author
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Catar R, Herse-Naether M, Zhu N, Wagner P, Wischnewski O, Kusch A, Kamhieh-Milz J, Eisenreich A, Rauch U, Hegner B, Heidecke H, Kill A, Riemekasten G, Kleinau G, Scheerer P, Dragun D, and Philippe A
- Subjects
- Blood Coagulation drug effects, Cell Proliferation drug effects, Endothelial Cells drug effects, Humans, Immunoglobulin G metabolism, MAP Kinase Signaling System drug effects, Models, Biological, Promoter Regions, Genetic genetics, Protein Binding drug effects, Thromboplastin metabolism, Autoantibodies pharmacology, Endothelial Cells cytology, Endothelial Cells metabolism, Proto-Oncogene Protein c-ets-1 metabolism, Receptor, Angiotensin, Type 1 metabolism, Receptor, Endothelin A metabolism
- Abstract
Scleroderma renal crisis (SRC) is an acute life-threatening manifestation of systemic sclerosis (SSc) caused by obliterative vasculopathy and thrombotic microangiopathy. Evidence suggests a pathogenic role of immunoglobulin G (IgG) targeting G-protein coupled receptors (GPCR). We therefore dissected SRC-associated vascular obliteration and investigated the specific effects of patient-derived IgG directed against angiotensin II type 1 (AT
1 R) and endothelin-1 type A receptors (ETA R) on downstream signaling events and endothelial cell proliferation. SRC-IgG triggered endothelial cell proliferation via activation of the mitogen-activated protein kinase (MAPK) pathway and subsequent activation of the E26 transformation-specific-1 transcription factor (Ets-1). Either AT1 R or ETA R receptor inhibitors/shRNA abrogated endothelial proliferation, confirming receptor activation and Ets-1 signaling involvement. Binding of Ets-1 to the tissue factor (TF) promoter exclusively induced TF. In addition, TF inhibition prevented endothelial cell proliferation. Thus, our data revealed a thus far unknown link between SRC-IgG-induced intracellular signaling, endothelial cell proliferation and active coagulation in the context of obliterative vasculopathy and SRC. Patients' autoantibodies and their molecular effectors represent new therapeutic targets to address severe vascular complications in SSc.- Published
- 2021
- Full Text
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139. Autoantibodies against M 5 -muscarinic and beta 1 -adrenergic receptors in periodontitis patients.
- Author
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Scherbaum I, Heidecke H, Bunte K, Peters U, Beikler T, and Boege F
- Subjects
- Adolescent, Adult, C-Reactive Protein analysis, Case-Control Studies, Female, Humans, Inflammation Mediators blood, Interleukin-6 blood, Male, Middle Aged, Natriuretic Peptide, Brain blood, Periodontitis blood, Periodontitis diagnosis, Periodontitis therapy, Prospective Studies, Treatment Outcome, Troponin I blood, Young Adult, Autoantibodies blood, Periodontitis immunology, Receptor, Muscarinic M5 immunology, Receptors, Adrenergic, beta-1 immunology
- Abstract
Autoantibodies against muscarinic and beta
1 -adrenergic receptors are considered a potential cause and/or risk factor for chronic heart failure. Association of periodontitis with such autoantibodies and with impaired heart function has been observed in patients exposed to endemic Chagas' disease, which triggers by itself cardiomyopathy and receptor immunization.Here we studied the association between periodontitis, markers of cardiac injury and receptor autoimmunization in periodontitis patients (n = 147) not exposed to Chagas' disease. The autoantibodies were determined by IgG binding to native intact muscarinic and beta1 -adrenergic receptors or to a cyclic peptide mimicking the disease-relevant conformational autoepitope presented by the active beta1 -adrenergic receptor. Possible cardiac injury and inflammatory status were judged by serum levels of proBNP/Troponin I and CRP/IL-6, respectively. These parameters were analysed in healthy and periodontally diseased individuals as well as before and after periodontal therapy.Patients with periodontitis had significantly (p < 0.001) higher levels of autoantibodies against M5 -muscarinic and beta1 -adrenergic receptors, which further increased following periodontal therapy. Receptor autoantibodies were associated with increased inflammatory status but not with increased markers of cardiac injury. Thus, our data indicate that periodontitis triggers systemic inflammation, which is associated with receptor autoimmunization, and, independently thereof, with cardiac injury.- Published
- 2020
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140. Soluble (pro)renin receptor in elderly chronic heart failure patients.
- Author
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Obradovic D, Loncar G, Radenovic S, Tahirovic E, Heidecke H, Schulze-Forster K, Muller D, Busjahn A, Buttner P, Veskovic J, Zdravkovic M, Li H, Li S, Savkovic V, Pieske B, Dungen HD, and Dechend R
- Subjects
- Aged, Chronic Disease, Echocardiography methods, Female, Heart Failure diagnosis, Hospitalization statistics & numerical data, Humans, Male, Middle Aged, Renin-Angiotensin System physiology, Risk Factors, Stroke blood, Stroke Volume physiology, Ventricular Function, Left physiology, Heart Failure blood, Heart Failure physiopathology, Protein Precursors blood, Receptors, Cell Surface blood, Vacuolar Proton-Translocating ATPases blood
- Abstract
Overactivation of renin-angiotensin system (RAS) is one of the main pathophysiological features in the evolution of chronic heart failure (CHF). The (pro)renin receptor ((P)RR) represents an important player in a tissue renin-angiotensin system (tissue RAS), which mediates tissue injury through fibrosis and hypertrophy of the affected organs in CHF patients. In our study we used plasma samples from 556 elderly subjects with CHF and 198 healthy participants in order to evaluate prognostic and diagnostic potential of s(P)RR in setting of CHF. The patients with CHF showed significantly higher plasma levels of s(P)RR than the healthy volunteers (p=0.0005). We observed association between higher s(P)RR plasma concentrations and lower left ventricular ejection fraction and higher degree of left ventricular dilatation on baseline echocardiography examination of the CHF patients. Elderly CHF patients with higher baseline s(P)RR plasma concentration were at same risk for death, stroke and hospitalization due to heart failure worsening at mean follow-up from forty-eight months in comparison to low s(P)RR counterparts.
- Published
- 2020
- Full Text
- View/download PDF
141. Regulatory antibodies against GPCR in women ten years after early-onset preeclampsia.
- Author
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Birukov A, Muijsers HEC, Heidecke H, Drost JT, Cunnigham MW, Kraker K, Haase N, Frolova A, Müller DN, Herse F, Maas AHEM, and Dechend R
- Subjects
- Adult, Autoantibodies blood, Blood Pressure immunology, Cardiovascular Diseases physiopathology, Case-Control Studies, Enzyme-Linked Immunosorbent Assay, Female, Humans, Hypertension immunology, Hypertension physiopathology, Middle Aged, Pre-Eclampsia physiopathology, Pregnancy, Retrospective Studies, Risk Factors, Time Factors, Autoantibodies immunology, Cardiovascular Diseases immunology, Pre-Eclampsia immunology, Receptors, G-Protein-Coupled immunology
- Abstract
Preeclampsia is associated with an increased cardiovascular risk later in life. Anti-GPCR autoantibodies have been shown to contribute to the development of cardiovascular disease. We investigated whether anti-GPCR autoantibodies are elevated in women with a history of early-onset preeclampsia 8-11 years postpartum, and whether they correlate with clinical outcomes. We investigated data from the Preeclampsia Risk EValuation in FEMales cohort, a retrospective matched case-control study. Anti AT1R-, beta1AR-, ETAR-, PAR1- and CXCR3- autoantibodies were determined in 485 samples by using commercially available ELISA. Women with the lowest combined levels of autoantibodies and a history of early preeclampsia had significantly higher SBP, DBP and MAP (all p<0.001) compared to the controls. The individual titer levels of autoantibodies were not different between controls and former early PE groups 8-11 years postpartum. In conclusion, regulatory autoantibodies alone are not sufficient to explain hypertension or other cardiovascular pathologic conditions, but together with other risk factors such as a previous hypertensive pregnancy, lower levels of autoantibodies are associated with increased blood pressure.
- Published
- 2019
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142. Anti-ß1-Adrenoreceptor auto-Antibodies in elderly heart failure patients.
- Author
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Trippel TD, Mueller DN, Obradovic D, Edelmann F, Tahirovic E, Wilck N, Riemekasten G, Dragun D, Busjahn A, Heidecke H, Junker J, Pieske B, Dungen HD, and Dechend R
- Subjects
- Adrenergic beta-Antagonists therapeutic use, Aged, Aged, 80 and over, Biomarkers blood, Bisoprolol therapeutic use, Carvedilol therapeutic use, Enzyme-Linked Immunosorbent Assay, Female, Follow-Up Studies, Glomerular Filtration Rate, Heart Failure drug therapy, Heart Rate, Humans, Male, Treatment Outcome, Ventricular Function, Left, Autoantibodies blood, Heart Failure immunology, Receptors, Adrenergic, beta-1 immunology
- Abstract
An autoimmune reaction directed against the cardiac b1-adrenergic receptor (beta1-ADR) leading to the generation of autoantibodies (AA) against this G-coupled receptor has been described in patients with heart failure (HF). Agonist-like beta1-ADR-AA are associated with morbidity in HF patients and even predict mortality. Standardised and valid diagnostic tools to detect beta 1-ADR-AA in clinical routine are lacking. We used a novel ELISA approach to investigate beta 1-ADR-AA in a cohort of 574 HF patients of the CIBIS-ELD trial with follow up. The CIBIS-ELD trial compared the titration of bisoprolol and carvedilol to recommended target doses in regard to BB tolerability in patients aged 65 years and older. Patient with left ventricular (LV) ejection fraction (EF) less than 50% or LV diameter end diastolic (DED) more than 55 cm showed significantly higher levels of beta1-ADR-AA. Although not yet fully validated, this ELISA allowed for a negative correlation of beta1-ADR-AA with the EF at baseline and at the follow up, beta1-ADR-AA further correlated positively with basal heart rate at follow up 12 weeks later. beta1-ADR-AA levels thus determined significantly increased under titration with beta-blockers (pless than 0.01). Changes in beta1-ADR-AA between F-Up and baseline were significantly higher in patients who used beta blockers (p=0.016) before study inclusion. The type of beta-blocker titrated in this study did not affect log beta1-ADR-AA levels at baseline (p=0.132), follow-up (p=0.058), nor the change (p=0.426). beta1-ADR-AA levels were estimated using a novel, commercially available ELISA. Although not yet fully validated, this ELISA allowed for pathophysiological insights: beta1-ADR-AA levels thus determined significantly increased under titration with beta-blockers (pless than 0.01), irrespective of type of BB. Higher levels of beta1-ADR-AA at baseline are associated with higher heart rates, lower ejection fraction and enlarged left ventricles. The relevance of the beta1-ADR-AA biomarker should be further evaluated.
- Published
- 2019
- Full Text
- View/download PDF
143. Loss of balance in normal GPCR-mediated cell trafficking.
- Author
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Cabral-Marques O, Carvalho-Marques AH, Schimke LF, Heidecke H, and Riemekasten G
- Subjects
- Animals, Autoantibodies metabolism, Autoimmune Diseases metabolism, Cytokines immunology, Cytokines metabolism, Humans, Inflammation Mediators immunology, Inflammation Mediators metabolism, Models, Immunological, Receptors, Chemokine immunology, Receptors, Chemokine metabolism, Receptors, G-Protein-Coupled metabolism, Autoantibodies immunology, Autoimmune Diseases immunology, Cell Movement immunology, Receptors, G-Protein-Coupled immunology
- Abstract
G protein-coupled receptors (GPCRs) form a most diverse family of integral membrane proteins that mediate homeostatic and pathological processes, most notably by orchestrating cell distribution throughout the body, their infiltration, and time of presence in inflamed tissues. Here we discuss loss-of-orientation-effects in GPCR-mediated cell trafficking and migration and their impact on the phenotype of autoimmune diseases. In this context, we provide a systemic and integrative view of the contribution of abnormal GPCR expression as well as the levels of natural ligands and functional autoantibodies to the phenotype of autoimmune diseases. Currently, several studies propose that functional autoantibodies (including those targeting GPCRs) constitute an exclusively pathogenic or pathognomonic phenomenon. Here we reinforce the need of revising this point of view, and suggest that functional autoantibodies primary play a role in normal human physiology, while dysregulation of their functions causes autoimmune disease. Because patients with autoimmune diseases still suffer from severe morbidity and mortality rates, we consider expanding our knowledge on (patho)physiological roles of GPCR as a prerequisite for the development of novel specific therapeutic modalities.
- Published
- 2019
- Full Text
- View/download PDF
144. Antibodies Against GPCR.
- Author
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Meyer C and Heidecke H
- Subjects
- Animals, Autoantibodies metabolism, Autoimmune Diseases diagnosis, Autoimmune Diseases immunology, Autoimmune Diseases metabolism, Biomarkers metabolism, Cardiovascular Diseases diagnosis, Cardiovascular Diseases immunology, Cardiovascular Diseases metabolism, Humans, Ligands, Nervous System Diseases diagnosis, Nervous System Diseases immunology, Nervous System Diseases metabolism, Receptors, G-Protein-Coupled metabolism, Autoantibodies immunology, Biomarkers analysis, Receptors, G-Protein-Coupled immunology, Signal Transduction immunology
- Abstract
G-protein-coupled receptors (GPCRs) are the largest family of receptors in humans. GPCRs are seven-transmembrane receptors that are activated by the binding of a ligand to the extracellular domain. In addition to the endogenous ligands, auto-antibodies (aab) can also bind to the GPCRs. They can activate different and specific cellular pathways which contribute to various diseases. In this review, the authors summarize the knowledge about antibodies targeting GPCRs and their effects and relevance in the pathogenesis of various diseases and their use in clinical diagnostics. We highlight the role of different activating anti-GPCR aab in solid organ transplantations, stem cell transplantations, systemic sclerosis, preeclampsia, chronic fatigue syndrome, cardiovascular diseases, Alzheimer's disease, and cancer.
- Published
- 2018
- Full Text
- View/download PDF
145. Antibodies to β adrenergic and muscarinic cholinergic receptors in patients with Chronic Fatigue Syndrome.
- Author
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Loebel M, Grabowski P, Heidecke H, Bauer S, Hanitsch LG, Wittke K, Meisel C, Reinke P, Volk HD, Fluge Ø, Mella O, and Scheibenbogen C
- Subjects
- Adrenergic Agents, Adult, B-Lymphocytes immunology, Case-Control Studies, Cholinergic Agents, Cohort Studies, Fatigue Syndrome, Chronic blood, Fatigue Syndrome, Chronic drug therapy, Female, Humans, Immunoglobulin G blood, Immunoglobulin G immunology, Male, Norepinephrine metabolism, Rituximab therapeutic use, Autoantibodies blood, Fatigue Syndrome, Chronic immunology, Receptors, Adrenergic, beta immunology, Receptors, Muscarinic immunology
- Abstract
Infection-triggered disease onset, chronic immune activation and autonomic dysregulation in CFS point to an autoimmune disease directed against neurotransmitter receptors. Autoantibodies against G-protein coupled receptors were shown to play a pathogenic role in several autoimmune diseases. Here, serum samples from a patient cohort from Berlin (n=268) and from Bergen with pre- and post-treatment samples from 25 patients treated within the KTS-2 rituximab trial were analysed for IgG against human α and β adrenergic, muscarinic (M) 1-5 acetylcholine, dopamine, serotonin, angiotensin, and endothelin receptors by ELISA and compared to a healthy control cohort (n=108). Antibodies against β2, M3 and M4 receptors were significantly elevated in CFS patients compared to controls. In contrast, levels of antibodies against α adrenergic, dopamine, serotonin, angiotensin, and endothelin receptors were not different between patients and controls. A high correlation was found between levels of autoantibodies and elevated IgG1-3 subclasses, but not with IgG4. Further patients with high β2 antibodies had significantly more frequently activated HLA-DR+ T cells and more frequently thyreoperoxidase and anti-nuclear antibodies. In patients receiving rituximab maintenance treatment achieving prolonged B-cell depletion, elevated β2 and M4 receptor autoantibodies significantly declined in clinical responder, but not in non-responder. We provide evidence that 29.5% of patients with CFS had elevated antibodies against one or more M acetylcholine and β adrenergic receptors which are potential biomarkers for response to B-cell depleting therapy. The association of autoantibodies with immune markers suggests that they activate B and T cells expressing β adrenergic and M acetylcholine receptors. Dysregulation of acetylcholine and adrenergic signalling could also explain various clinical symptoms of CFS., (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2016
- Full Text
- View/download PDF
146. The utility of an in vitro angiogenesis score for prognosis assessment in patients with cervical cancer.
- Author
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Landt S, Heidecke H, Reuter C, Korlach S, Blohmer JU, Lichtenegger W, Heusner T, Stöblen F, Thill M, Barinoff J, Sehouli J, and Kümmel S
- Subjects
- Cells, Cultured, Endostatins blood, Enzyme-Linked Immunosorbent Assay, Female, Fibroblast Growth Factor 2 blood, Humans, Prognosis, Receptors, Vascular Endothelial Growth Factor blood, Uterine Cervical Neoplasms blood, Uterine Cervical Neoplasms pathology, Vascular Endothelial Growth Factor A blood, Neovascularization, Pathologic, Uterine Cervical Neoplasms blood supply
- Abstract
Background/aim: Angiogenesis plays a key role in tumour growth and metastasis. Expression of angiogenic factors has been suggested as a marker for tumour malignity, and may help to assess a patient's individual prognosis. The present study examines the relationship between angiogenic factor expression, an angiogenesis-based histoscore and clinical tumour criteria., Patients and Methods: A total of 81 patients with cervical cancer who underwent follow-up examinations between October 2002, and June 2005, were enrolled, and serum samples were examined for vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), endostatin and VEGF-Receptor1 by means of an ELISA. Based on an endothelial-cell proliferation assay, an angiogenesis score was calculated., Results: Higher endostatin and VEGF expressions indicated advanced disease, and VEGF allowed for a reliable distinction between patients with non-invasive and these with recurrent disease. There were some plausible correlations between the angiogenesis score and clinical criteria and individual angiogenic factors, but the score's discriminating power appears to be limited., Conclusion: The utility of angiogenesis factor testing notwithstanding, the value of an angiogenesis score for the identification of patients with a worse prognosis, and thus a resulting benefit from more aggressive treatment, is arguable.
- Published
- 2011
147. Prognostic significance of angiogenic factors in uterine cervical cancer.
- Author
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Landt S, Wehling M, Heidecke H, Jeschke S, Korlach S, Stöblen F, Schmid P, Blohmer JU, Lichtenegger W, Sehouli J, and Kümmel S
- Subjects
- Adult, Female, Humans, Middle Aged, Neoplasm Invasiveness, Prognosis, Uterine Cervical Neoplasms drug therapy, Uterine Cervical Neoplasms pathology, Angiogenesis Inhibitors therapeutic use, Angiogenic Proteins blood, Uterine Cervical Neoplasms blood
- Abstract
Background/aim: Angiogenesis is pivotal in tumour development and progress, and targeted tumour therapies, such as bevacizumab, have shown promising results. However, in unselected patient populations, the treatment with angiogenesis-targeted combination regimens is marred by a variable response, non-negligible toxicity and questionable economy. The present study summarizes research to identify individual circulating angiogenic factors as markers for disease severity and possibly treatment response., Patients and Methods: A total of 125 patients with cervical cancer from the ongoing cervical cancer monitoring database of the University Hospital Charité, Berlin, Germany, were included. Information obtained from the database included tumour stage, malignancy grade, presence of nodal metastases, lymph vessel invasion, patient age, HER2, HPV, smoking and menopausal status, and serum concentrations of vascular endothelial growth factor (VEGF), VEGF-D, VEGF-C, endoglin, endostatin, angiogenin, basic fibroblast growth factor (FGFb), vascular endothelial growth factor receptor (VEGF-R1), VEGF-R2, soluble inter-cellular adhesion molecule 1 (sICAM 1), soluble vascular adhesion molecule 1 (sVCAM 1), insulin-like growth factor 1 (IFG-1) and insulin like growth factor binding protein 3 (IGF-BP3)., Results: There was a clear association of angiogenic factor concentrations with stage of disease. Angiogenin showed an independent discrimination for cervical intraepithelial neoplasia (CIN) and invasive stages, and endoglin did so for invasive stages vs. recurrent disease. However, none of the potential markers under investigation was anywhere near selective enough to allow for a clinically meaningful prediction of prognosis or response., Conclusion: The association of circulating angiogenic factors with disease progression in cervical cancer is confirmed, but its utility for prognosis prediction and patient stratification for targeted therapies is doubtful.
- Published
- 2011
148. In vitro vascular tube formation testing as a tool for treatment individualisation in patients with cervical cancer.
- Author
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Landt S, Heidecke H, Korlach S, Reuter C, Schwidde I, Barinoff J, Thill M, Sehouli J, and Kümmel S
- Subjects
- Antibodies, Monoclonal, Humanized, Bevacizumab, Cells, Cultured, Endostatins blood, Female, Fibroblast Growth Factor 2 blood, Humans, Uterine Cervical Neoplasms blood supply, Vascular Endothelial Growth Factor A blood, Angiogenesis Inhibitors therapeutic use, Antibodies, Monoclonal therapeutic use, Endothelium, Vascular pathology, Uterine Cervical Neoplasms drug therapy
- Abstract
Background/aim: Targeted tumour therapies are promising, but their results in unselected patient populations are modest and tumour growth and metastasis may be promoted rather than suppressed in some cases. The present study investigates the suitability of vascular in vitro tube formation as a tool for the identification of cervical neoplasms that will respond to bevacizumab therapy., Patients and Methods: Fifteen patients with recurrent cervical cancer selected from the ongoing cervical cancer monitoring database of the Charité University Hospital Berlin, Germany, were included. Information obtained from the database included tumour stage, malignancy grade, presence of nodal metastases, lymph vessel invasion, patient age and menopausal status and serum concentrations of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), endostatin and vascular endothelial growth factor receptor 1 (VEGF-R1). Vascular tube formation was assessed with cultured human umbilical vein epithelial cells., Results: Five patients showed a positive, 5 an inverse and 5 no in vitro response to bevacizumab. Tube length showed a marked and significant dependency on bevacizumab response. Besides tube length, VEGF-R1 concentration was the only variable with some correlation to bevacizumab response, with high levels especially for inverse responders., Conclusion: The identification of patients with a likely benefit from targeted therapies is crucial. Tube formation shows substantial potential, but its utility needs to be confirmed in studies on the clinical rather than in vitro response to bevacizumab.
- Published
- 2011
149. Alpha1A-adrenergic receptor-directed autoimmunity induces left ventricular damage and diastolic dysfunction in rats.
- Author
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Wenzel K, Wallukat G, Qadri F, Hubner N, Schulz H, Hummel O, Herse F, Heuser A, Fischer R, Heidecke H, Luft FC, Muller DN, Dietz R, and Dechend R
- Subjects
- Amino Acid Sequence, Animals, Animals, Newborn, Autoantibodies immunology, Autoantibodies pharmacology, Blood Pressure, CHO Cells, Cricetinae, Cricetulus, Diastole, Electrocardiography, Enzyme-Linked Immunosorbent Assay, Gene Expression Profiling, Humans, Immunoglobulin G immunology, Male, Molecular Sequence Data, Myocardium immunology, Myocardium metabolism, Myocytes, Cardiac cytology, Myocytes, Cardiac drug effects, Myocytes, Cardiac physiology, Rats, Rats, Inbred Lew, Reverse Transcriptase Polymerase Chain Reaction, Autoimmunity immunology, Heart physiopathology, Myocardium pathology, Receptors, Adrenergic, alpha-1 immunology
- Abstract
Background: Agonistic autoantibodies to the alpha(1)-adrenergic receptor occur in nearly half of patients with refractory hypertension; however, their relevance is uncertain., Methods/principal Findings: We immunized Lewis rats with the second extracellular-loop peptides of the human alpha(1A)-adrenergic receptor and maintained them for one year. Alpha(1A)-adrenergic antibodies (alpha(1A)-AR-AB) were monitored with a neonatal cardiomyocyte contraction assay by ELISA, and by ERK1/2 phosphorylation in human alpha(1A)-adrenergic receptor transfected Chinese hamster ovary cells. The rats were followed with radiotelemetric blood pressure measurements and echocardiography. At 12 months, the left ventricles of immunized rats had greater wall thickness than control rats. The fractional shortening and dp/dt(max) demonstrated preserved systolic function. A decreased E/A ratio in immunized rats indicated a diastolic dysfunction. Invasive hemodynamics revealed increased left ventricular end-diastolic pressures and decreased dp/dt(min). Mean diameter of cardiomyocytes showed hypertrophy in immunized rats. Long-term blood pressure values and heart rates were not different. Genes encoding sarcomeric proteins, collagens, extracellular matrix proteins, calcium regulating proteins, and proteins of energy metabolism in immunized rat hearts were upregulated, compared to controls. Furthermore, fibrosis was present in immunized hearts, but not in control hearts. A subset of immunized and control rats was infused with angiotensin (Ang) II. The stressor raised blood pressure to a greater degree and led to more cardiac fibrosis in immunized, than in control rats., Conclusions/significance: We show that alpha(1A)-AR-AB cause diastolic dysfunction independent of hypertension, and can increase the sensitivity to Ang II. We suggest that alpha(1A)-AR-AB could contribute to cardiovascular endorgan damage.
- Published
- 2010
- Full Text
- View/download PDF
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