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4. Gene Expression–Based Molecular Test as Diagnostic Aid for the Differential Diagnosis of Psoriasis and Eczema in Formalin-Fixed and Paraffin-Embedded Tissue, Microbiopsies, and Tape Strips

Author

Fischer, Felix, Doll, Anais, Uereyener, Deniz, Roenneberg, Sophie, Hillig, Christina, Weber, Lucca, Hackert, Verena, Meinel, Martin, Farnoud, Ali, Seiringer, Peter, Thomas, Jenny, Anand, Philipp, Graner, Larissa, Schlenker, Franziska, Zengerle, Roland, Jonsson, Pontus, Jargosch, Manja, Theis, Fabian J., Schmidt-Weber, Carsten B., Biedermann, Tilo, Howell, Michael, Reich, Kristian, Eyerich, Kilian, Menden, Michael, Garzorz-Stark, Natalie, Lauffer, Felix, and Eyerich, Stefanie

Published
2023
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7. Noninferiority of 16-Week vs 8-Week Guselkumab Dosing in Super Responders for Maintaining Control of Psoriasis: The GUIDE Randomized Clinical Trial.

Author

Eyerich, Kilian, Asadullah, Khusru, Pinter, Andreas, Weisenseel, Peter, Reich, Kristian, Paul, Carle, Sabat, Robert, Wolk, Kerstin, Eyerich, Stefanie, Lauffer, Felix, Angsana, Julianty, Taut, Friedemann J. H., Kohler, Kristen, Chen, Yanqing, Sendecki, Jocelyn, Leung, Monica W. L., Wegner, Sven, Personke, Yvonne, Gomez, Mario, and Krüger, Nenja

Published
2024
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8. Der Einfluss von Metastasierungsmustern und Tumorlast auf die therapeutische Effektivität und das Therapieansprechen der Immuntherapie bei Patienten mit metastasiertem malignen Melanom, untersucht mithilfe quantitativer PET-Parameter

Author

Nekolla, Stephan (Prof. Dr.), Nekolla, Stephan (Prof. Dr.);Lauffer, Felix (Priv.-Doz. Dr., Ph.D.);Ziegler, Sibylle (Prof. Dr.), Berberich, Cornelius Benedikt Johannes, Nekolla, Stephan (Prof. Dr.), Nekolla, Stephan (Prof. Dr.);Lauffer, Felix (Priv.-Doz. Dr., Ph.D.);Ziegler, Sibylle (Prof. Dr.), and Berberich, Cornelius Benedikt Johannes

Abstract

Der Einsatz der Immuntherapie mit Checkpoint-Inhibitoren hat die Therapie des metastasierten malignen Melanoms revolutioniert. Dennoch gibt es aktuell wenige klinische Parameter, die eine Vorhersage des Therapieansprechens ermöglichen. Ziel war daher, Metastasierungsmuster als mögliche Einflussfaktoren auf Ansprechen und Überleben zu untersuchen. Das Therapieansprechen wurden mithilfe metabolischer Parameter aus der 18F-FDG PET/CT-Bildgebung quantifiziert und in multivariaten Analysen evaluiert., The introduction of immunotherapy with immune checkpoint inhibitors revolutionized the treatment of metastatic melanoma. Nevertheless, currently, there are only few clinical parameters to predict response to immunotherapy. This thesis aimed to identify metastatic patterns that can predict response and survival. Metastatic patterns and responses were quantified using metabolic parameters from 18F-FDG PET/CT imaging and evaluated in multivariate analyses.

Published
2024

9. Vergleich unterschiedlicher Biopsietechniken zur molekularen Diagnostik bei chronisch entzündlichen Hauterkrankungen

Author

Eyerich, Kilian (Prof. Dr., Ph.D.), Eyerich, Kilian (Prof. Dr., Ph.D.);Lauffer, Felix (Priv.-Doz. Dr., Ph.D.), Doll, Anaïs Marie Theresa, Eyerich, Kilian (Prof. Dr., Ph.D.), Eyerich, Kilian (Prof. Dr., Ph.D.);Lauffer, Felix (Priv.-Doz. Dr., Ph.D.), and Doll, Anaïs Marie Theresa

Abstract

Ziel dieser Arbeit war es im Bereich der Diagnostik von Psoriasis und Atopisches Ekzem Microbiopsien (1mm Durchmesser) mit Macrobiopsien (4-6mm Durchmesser) unter verschiedenen Blickpunkten zu vergleichen. Microbiopsien zeigten sich als vielversprechendes Toll: histologisch wurden pathognomonische Merkmale erkannt. In den Sequenzierungsdaten konnte kein signifikanter Unterschied gezeigt werden und durch den Molecular Classifier wurden die Proben mehrheitlich richtig diagnostiziert. Auch Patienten bevorzugten die Microbiopsie Entnahme., The aim of the study was to compare microbiopsies (1mm diameter) with macrobiopsies (4-6mm diameter) from different points of view in the field of psoriasis and atopic eczema diagnotic. Microbiopsies turned out as a promising tool: pathognomonic features were detected histologically. No significant difference could be shown in the sequencing data and the Molecular Classifier diagnosed the majority of samples correctly. Patients also preferred microbiopsy sampling.

Published
2024

10. Characterization of High and Low IFNG-Expressing Subgroups in Atopic Dermatitis.

Author

Wasserer, Sophia, Jargosch, Manja, Mayer, Kristine E., Eigemann, Jessica, Raunegger, Theresa, Aydin, Görkem, Eyerich, Stefanie, Biedermann, Tilo, Eyerich, Kilian, and Lauffer, Felix

Subjects
ATOPIC dermatitis, KILLER cells, T cells, GENE expression, LIPID synthesis, RNA sequencing
Abstract

Atopic dermatitis (AD) is one of the most common chronic inflammatory skin diseases, with an increasing number of targeted therapies available. While biologics to treat AD exclusively target the key cytokines of type 2 immunity, Janus kinase inhibitors target a broad variety of cytokines, including IFN-γ. To better stratify patients for optimal treatment outcomes, the identification and characterization of subgroups, especially with regard to their IFNG expression, is of great relevance, as the role of IFNG in AD has not yet been fully clarified. This study aims to define AD subgroups based on their lesional IFNG expression and to characterize them based on their gene expression, T cell secretome and clinical attributes. RNA from the lesional and non-lesional biopsies of 48 AD patients was analyzed by RNA sequencing. Based on IFNG gene expression and the release of IFN-γ by lesional T cells, this cohort was categorized into three IFNG groups (high, medium, and low) using unsupervised clustering. The low IFNG group showed features of extrinsic AD with a higher prevalence of atopic comorbidities and impaired epidermal lipid synthesis. In contrast, patients in the high IFNG group had a higher average age and an activation of additional pro-inflammatory pathways. On the cellular level, higher amounts of M1 macrophages and natural killer cell signaling were detected in the high IFNG group compared to the low IFNG group by a deconvolution algorithm. However, both groups shared a common dupilumab response gene signature, indicating that type 2 immunity is the dominant immune shift in both subgroups. In summary, high and low IFNG subgroups correspond to intrinsic and extrinsic AD classifications and might be considered in the future for evaluating therapeutic efficacy or non-responders. [ABSTRACT FROM AUTHOR]

Published
2024
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13. Toll-like receptor 7/8 agonists stimulate plasmacytoid dendritic cells to initiate TH17-deviated acute contact dermatitis in human subjects

Author

Garzorz-Stark, Natalie, Lauffer, Felix, Krause, Linda, Thomas, Jenny, Atenhan, Anne, Franz, Regina, Roenneberg, Sophie, Boehner, Alexander, Jargosch, Manja, Batra, Richa, Mueller, Nikola S., Haak, Stefan, Groß, Christina, Groß, Olaf, Traidl-Hoffmann, Claudia, Theis, Fabian J., Schmidt-Weber, Carsten B., Biedermann, Tilo, Eyerich, Stefanie, and Eyerich, Kilian

Published
2018
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15. Überlebensanalysen von Patienten mit metastasiertem malignem Melanom unter Immuntherapie und Targeted Therapies im Rahmen einer FDG-PET/CT Ganzkörper-Untersuchung und Beurteilung des Ansprechens auf Immuntherapie mittels PET- und CT-Parameter in einzelnen Läsionen

Author

Nekolla, Stephan (Prof. Dr.), Nekolla, Stephan (Prof. Dr.);Lauffer, Felix (Priv.-Doz. Dr., Ph.D.), Zhuwu, Yize, Nekolla, Stephan (Prof. Dr.), Nekolla, Stephan (Prof. Dr.);Lauffer, Felix (Priv.-Doz. Dr., Ph.D.), and Zhuwu, Yize

Abstract

In dieser Arbeit bestätigten wir, dass das Auftreten von immune-related Adverse Events (irAEs), insbesondere von FDG aviden irAEs, im Rahmen der Immuntherapie bei Patienten mit metastasiertem malignem Melanom mit einem besseren progressionsfreien Überleben und tendenziell auch einem besseren Gesamtüberleben assoziiert ist. Um ferner herauszufinden, ob PET- und CT-Parameter ein prädiktives Mittel zur Beurteilung von Therapieansprechen sind, verglichen wir in einzelnen Läsionen die Differenzen dieser Parameter, gebildet aus dem Messwert nach und vor der eingeleiteten Immuntherapie. Einige Parameterdifferenzen wiesen signifikante Unterschiede zwischen Responder- und Nonresponderläsionen auf., In this dissertation, we confirmed that the occurrence of immune-related adverse events (irAEs), in particular FDG avid irAEs, in the setting of immunotherapy in patients with metastatic malignant melanoma is associated with a better progression free survival and tends to be associated with better overall survival. In order to determine whether PET and CT parameters are predictive of treatment response, we compared the differences in those parameters, formed from the measured value after and before the initiated immunotherapy, in individual lesions. Some parameter differences were significantly different between responder and nonresponder lesions.

Published
2023

16. The neglected twin: nummular eczema is a variant of atopic dermatitis with co-dominant Th2/Th17 immune response

Author

Böhner, Alexander, primary, Jargosch, Manja, additional, Müller, Nikola S., additional, Garzorz-Stark, Natalie, additional, Pilz, Caroline, additional, Lauffer, Felix, additional, Wang, Rosi, additional, Roenneberg, Sophie, additional, Zink, Alexander, additional, Thomas, Jenny, additional, Theis, Fabian J., additional, Biedermann, Tilo, additional, Eyerich, Stefanie, additional, and Eyerich, Kilian, additional

Published
2023
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18. IRAK4 inhibition dampens pathogenic processes driving inflammatory skin diseases

Author

Lavazais, Stéphanie, primary, Jargosch, Manja, additional, Dupont, Sonia, additional, Labéguère, Frédéric, additional, Menet, Christel, additional, Jagerschmidt, Catherine, additional, Ohm, Frenz, additional, Kupcsik, Laszlo, additional, Parent, Isabelle, additional, Cottereaux, Céline, additional, Marsais, Florence, additional, Oste, Line, additional, Van de Water, An, additional, Christophe, Thierry, additional, De Vos, Steve, additional, Fallon, Padraic, additional, Lauffer, Felix, additional, Clément-Lacroix, Philippe, additional, Eyerich, Kilian, additional, and Brys, Reginald, additional

Published
2023
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20. A comparison between nailfold capillaroscopy patterns in adulthood in juvenile and adult-onset systemic sclerosis: A EUSTAR exploratory study

Author

Airò, Paolo, Alegre-Sancho, Juan Jose, Allanore, Yannick, Ananieva, Lidia P., Ancuta, Codrina, Andrade, Luis Eduardo, Aringer, Martin, Becvar, Radim, Bojinca, Mihai, Butrimiene, Irena, Cantatore, Francesco Paolo, Caporali, Roberto, Caramaschi, Paola, Carreira, Patricia E., Chirieac, Rodica, Corrado, Ada, Cosentino, Vanesa, Cuomo, Giovanna, Czirjak, Laszlo, Da Silva, José Antonio Pereira, la Peña Lefebvre, Paloma García de, De Keyser, Filip, de Souza Müller, Carolina, Damgaard, Kirsten, Damjanov, Nemanja, Denisov, Lev N., Distler, Oliver, Doube, Alan, Dumitrascu, Alina, Engelhart, Merete, Exposito, Marta Valero, Eyerich, Kilian, Farge-Bancel, Dominique, Azevedo, Valderílio Feijó, Foti, Rosario, Frerix, Marc, Gabrielli, Armando, Garen, Torhild, Gottschalk, Paola, Groseanu, Laura, Guiducci, Serena, Günther, Claudia, Hachulla, Eric, Hein, Rüdiger, Heitmann, Stefan, Henes, Jörg, Hesselstrand, Roger, Highton, John, Iannone, Florenzo, Ionescu, Ruxandra Maria, Kayser, Cristiane, Karpec, Diana, Kerzberg, Eduardo, Kotulska, Anna, Kopec-Medrek, Magdalena, Kucharz, Eugene, Krummel-Lorenz, Brigitte, Lauffer, Felix, Launay, David, Li, Mengtao, Litinsky, Ira, Loyo, Esthela, Cerinic, Marco Matucci, Meroni, Pierluigi, Midtvedt, Øyvind, Mihai, Carmen Marina, Montecucco, Carlomaurizio, Montoya, Fabiana, Morgiel, Ewa, Mouthon, Luc, Müller-Ladner, Ulf, Nielsen, Henrik, Opris, Daniela, Ortiz-Santamaria, Vera, Otsa, Kati, Pileckyte, Margarita, Pisarri, Simonetta, Popescu, Monica, Pozzi, Maria Rosa, Puppo, Francesco, Radominski, Sebastião Cezar, Riccieri, Valeria, Rosato, Edoardo, Rozman, Blaz, Rubio, Silvia Rodriguez, Rugiene, Rita, Saar, Petra, Salvador, Maria João, Seidel, Matthias, Sokolik, Renata, Solanki, Kamal, Stamenkovic, Bojana, Stankovic, Aleksandra, Stebbings, Simon, Strauss, Gitte, Sulli, Alberto, Szamosi, Szilvia, Szechinski, Jacek, Szmyrka-Kaczmarek, Magdalena, Szücs, Gabriella, Tanaseanu, Cristina-Mihaela, Tiglea, Isabela, Tyndall, Alan, Ughi, Nicola, Uprus, Maria, Vacca, Alessandra, Varju, Cecilia, Venalis, Algirdas, Venalis, Paulius, Walker, Ulrich A., Widuchowska, Malgorzata, Wiland, Piotr, Wuttge, Dirk M., Zeni, Silvana, Zenone, Thierry, Ingegnoli, Francesca, Boracchi, Patrizia, Gualtierotti, Roberta, Smith, Vanessa, Cutolo, Maurizio, and Foeldvari, Ivan

Published
2015
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22. Einschätzungen zur Therapie der moderaten bis schweren atopischen Dermatitis mit Januskinaseinhibitoren

Author

Lauffer, Felix and Biedermann, Tilo

Abstract

Hintergrund: Die atopische Dermatitis ist eine häufige chronisch entzündliche Hauterkrankung, die mit erheblichem Leidensdruck einhergeht. Januskinaseinhibitoren sind seit Kurzem für die Therapie der atopischen Dermatitis verfügbar. Fragestellung: Es erfolgen eine Zusammenfassung der bisherigen Daten zur Wirksamkeit und Sicherheit von Januskinaseinhibitoren zur Therapie der atopischen Dermatitis sowie Darstellung praktischer Hinweise zum klinischen Einsatz. Material und Methoden: Es werden eine Zusammenfassung und Bewertung der aktuell verfügbaren Datenlage gegeben. Ergebnisse: Drei Januskinaseinhibitoren sind zur Therapie der mittelschweren bis schweren atopischen Dermatitis zugelassen: Baricitinib, Upadacitinib und Abrocitinib. In den Zulassungsstudien und ersten Real-Life-Erfahrungen wurden eine starke und schnelle Reduktion des Juckreizes und der klinischen Zeichen der atopischen Dermatitis sowie positive Effekte auf die Lebensqualität betroffener Personen demonstriert. Das aktuelle Sicherheitsprofil zeigt sich günstig, wobei jedoch Langzeitsicherheitsdaten speziell für den Einsatz bei der atopischen Dermatitis aktuell noch nicht verfügbar sind. Schlussfolgerungen: Januskinaseinhibitoren bereichern das therapeutische Spektrum bei der Behandlung der atopischen Dermatitis. Unter Beachtung der Kontraindikationen, Nebenwirkungen und notwendigen Laboruntersuchungen stellen sie eine hocheffektive und sichere Therapieoption für betroffene Patienten dar.

Published
2024
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30. Gene expression based molecular test proves clinical validity as diagnostic aid for the differential diagnosis of psoriasis and eczema in formalin fixed and paraffin embedded tissue

Author

Fischer, Felix, primary, Roenneberg, Sophie, additional, Graner, Larissa, additional, Schlenker, Franziska, additional, Zengerle, Roland, additional, Theis, Fabian J., additional, Schmidt-Weber, Carsten B., additional, Biedermann, Tilo, additional, Lauffer, Felix, additional, Garzorz-Stark, Natalie, additional, and Eyerich, Stefanie, additional

Published
2022
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37. Death associated protein kinase 1 dampens keratinocyte necroptosis and expression of inflammatory genes in lichen planus

Author

Kurzen, Nils, Mubarak, Menna, Eigemann, Jessica, Seiringer, Peter, Wasserer, Sophia, Hillig, Christina, Menden, Michael, Biedermann, Tilo, Schmidt-Weber, Carsten B., Eyerich, Kilian, Jargosch, Manja, Eyerich, Stefanie, and Lauffer, Felix

Abstract

Lichen planus (LP) is a chronic inflammatory disease (ISD) affecting skin, mucosa, nail, and hair. Previous studies demonstrated a pivotal role of type 1 immunity in LP, as infiltrating T cells trigger apoptosis and necroptosis in the epidermis. In this study, we investigated the role of DAPK1 in LP with special focus on its role in mediating cell death and inflammation.

Published
2025
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38. Predicting persistence of atopic dermatitis in children using clinical attributes and serum proteins

Author

Lauffer, Felix, primary, Baghin, Veronika, additional, Standl, Marie, additional, Stark, Sebastian P., additional, Jargosch, Manja, additional, Wehrle, Julius, additional, Thomas, Jenny, additional, Schmidt‐Weber, Carsten B., additional, Biedermann, Tilo, additional, Eyerich, Stefanie, additional, Eyerich, Kilian, additional, and Garzorz‐Stark, Natalie, additional

Published
2020
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39. Integration of phenomics and transcriptomics data to reveal drivers of inflammatory processes in the skin

Author

Batra, Richa, primary, Garzorz-Stark, Natalie, additional, Lauffer, Felix, additional, Jargosch, Manja, additional, Pilz, Caroline, additional, Roenneberg, Sophie, additional, Schäbitz, Alexander, additional, Böhner, Alexander, additional, Seiringer, Peter, additional, Thomas, Jenny, additional, Fereydouni, Bentolhoda, additional, Kutkaite, Ginte, additional, Menden, Michael, additional, Tsoi, Lam C, additional, Gudjonsson, Johann E, additional, Theis F, Fabian, additional, Biedermann, Tilo, additional, Schmidt-Weber, Carsten B, additional, Müller, Nikola, additional, Eyerich, Stefanie, additional, and Eyerich, Kilian, additional

Published
2020
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41. Cytokines of the IL‐17 family in psoriasis

Author

Lauffer, Felix, primary, Eyerich, Kilian, additional, Boehncke, Wolf‐Henning, additional, Asadullah, Khusru, additional, Beissert, Stefan, additional, Ghoreschi, Kamran, additional, and Schön, Michael P., additional

Published
2020
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42. Psoriasis as a Systemic Disease.

Author

Mrowietz, Ulrich, Gerdes, Sascha, Lauffer, Felix, Sondermann, Wiebke, and Sewerin, Philip

Abstract

Background: Psoriasis was long regarded as an inflammatory disease limited to the skin. Data from dermatologic, rheumatologic and cardiologic research now show it to be a systemic disease, for which the term psoriatic disease is used. Methods: This paper is based on a selective literature search with special attention to the findings of clinical trials and other current publications, as well as the recommendations of international guidelines. Results: Immunologically mediated inflammation of the skin, arteries, bones, and joints is a central feature of psoriatic disease. Other diseases that are known to be associated with psoriatic disease include hypertension, metabolic syndrome, and depression. The main risk factor for the development of psoriatic disease is obesity, which also increases the likelihood of psoriatic arthritis. The main known trigger factors are stress, infection, and, less commonly, medication. Psoriatic disease is characterized by complex genetics and by a characteristic pattern of inflammation that involves elements of both innate and acquired immunity and, in particular, the cytokines interleukin 17 and 23. The inflammatory processes underlying psoriatic disease can now be targeted with modern biologic and other therapies. Conclusion: In view of the complexity of psoriatic disease, structured management is now recommended so that physicians and patients can work together to determine the optimal treatment strategy. [ABSTRACT FROM AUTHOR]

Published
2024
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43. Exogene und endogene Einflussaktoren von spezifischen immunologischen Reaktionsmustern der Haut bei entzündlichen Hauterkrankungen

Author

Lauffer, Felix, Eyerich, Kilian G. (Prof. Dr.), Biedermann, Tilo (Prof. Dr.), and Schmidt-Weber, Carsten (Prof. Dr.)

Subjects
Medizin und Gesundheit, ddc:610
Abstract

Inflammatory skin diseases are frequent in western countries and severely impact patient's quality of life. This thesis describes how exogenous, endogenous and epithelial derived immune triggers shape general inflammation patterns of the skin. Characterizing skin diseases by their immune polarization and not by historical disease names is an important step to identify new drug targets, to transfer therapeutic concepts to rare diseases and to develop precision medicine in clinical practice. Entzündliche Hauterkrankungen sind häufig in westlichen Ländern und mindern stark die Lebensqualität betroffener Personen. Diese Dissertation beschreibt wie exogene, endogene und Epithel-spezifische Einflüsse generelle Entzündungsreaktionen der Haut vermitteln. Die Charakterisierung von Hauterkrankungen gemäß ihrer immunologischen Richtung und nicht an Hand historischer Krankheitsnamen ermöglicht die Identifizierung neuer therapeutischer Angriffspunkte, den Transfer von etablierten Therapien zu seltenen Erkrankungen und die Entwicklung von präzisions-gerichteter Medizin in der klinischen Praxis.

Published
2018

45. Predicting persistence of atopic dermatitis in children using clinical attributes and serum proteins.

Author

Lauffer, Felix, Baghin, Veronika, Standl, Marie, Stark, Sebastian P., Jargosch, Manja, Wehrle, Julius, Thomas, Jenny, Schmidt‐Weber, Carsten B., Biedermann, Tilo, Eyerich, Stefanie, Eyerich, Kilian, and Garzorz‐Stark, Natalie

Subjects
*BLOOD proteins, *ATOPIC dermatitis, *DISEASE exacerbation, *AGE distribution, *K-means clustering
Abstract

Background: Atopic dermatitis (AD) is the most common inflammatory skin disease in children, with 30% of all those diagnosed developing chronic or relapsing disease by adolescence. Such disease persistence cannot yet be predicted. The aim of the present study was to predict the natural course of AD using clinical parameters and serum proteins. Methods: Sera of 144 children with AD (age 0‐3 years) were analyzed for IgE and 33 cytokines, chemokines, and growth factors. Patient disease course until the age of 7 years was assessed retrospectively. Unsupervised k‐means clustering was performed to define disease endotypes. Identified factors associated with AD persistence at the age of 7 years were validated in children with AD in an independent cohort (LISA Munich; n = 168). Logistic regression and XGBoosting methods followed by cross‐validation were applied to predict individual disease outcomes. Results: Three distinct endotypes were found in infancy, characterized by a unique inflammatory signature. Factors associated with disease persistence were disease score (SCORAD), involvement of the limbs, flexural lesion distribution at the age of 3 years, allergic comorbidities, and disease exacerbation by the trigger factors stress, pollen exposure, and change in weather. Persistence was predicted with a sensitivity of 81.8% and a specificity of 82.4%. Factors with a high impact on the prediction of persistence were SCORAD at the age of 3 years, trigger factors, and low VEGF serum levels. Conclusion: Atopic dermatitis in infancy comprises three immunological endotypes. Disease persistence can be predicted using serum cytokines and clinical variables. [ABSTRACT FROM AUTHOR]

Published
2021
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46. Exogenous and endogenous triggers of distinct reactions of skin immunity in inflammatory skin diseases

Author

Eyerich, Kilian G. (Prof. Dr.), Schmidt-Weber, Carsten (Prof. Dr.), Biedermann, Tilo (Prof. Dr.), Lauffer, Felix, Eyerich, Kilian G. (Prof. Dr.), Schmidt-Weber, Carsten (Prof. Dr.), Biedermann, Tilo (Prof. Dr.), and Lauffer, Felix

Abstract

Inflammatory skin diseases are frequent in western countries and severely impact patient's quality of life. This thesis describes how exogenous, endogenous and epithelial derived immune triggers shape general inflammation patterns of the skin. Characterizing skin diseases by their immune polarization and not by historical disease names is an important step to identify new drug targets, to transfer therapeutic concepts to rare diseases and to develop precision medicine in clinical practice., Entzündliche Hauterkrankungen sind häufig in westlichen Ländern und mindern stark die Lebensqualität betroffener Personen. Diese Dissertation beschreibt wie exogene, endogene und Epithel-spezifische Einflüsse generelle Entzündungsreaktionen der Haut vermitteln. Die Charakterisierung von Hauterkrankungen gemäß ihrer immunologischen Richtung und nicht an Hand historischer Krankheitsnamen ermöglicht die Identifizierung neuer therapeutischer Angriffspunkte, den Transfer von etablierten Therapien zu seltenen Erkrankungen und die Entwicklung von präzisions-gerichteter Medizin in der klinischen Praxis.

Published
2018

47. Transcriptome analysis of pyoderma gangrenosum reveals an activation of innate immunity, cell cycle and regulated cell death pathways

Author

Böhmer, Danielle, Lauffer, Felix, Batra, Richa, Jargosch, Manja, Österlin, Christian, Seiringer, Peter, and Eyerich, Kilian

Abstract

Pyoderma gangrenosum (PG) is an autoinflammatory disease leading to extremely painful and highly inflamed ulcers of the skin. Immune mechanisms driving chronic inflammation as well as optimal treatment strategies are still elusive. Here we performed RNA-sequencing analysis of 7 PG skin biopsies and 2 autologous non-involved skin samples. Gene expression was compared between the group of lesional versus non-lesional skin samples. Pathway analysis was performed using KEGG, Reactome, Biocarta and PID databases. For enrichment, all genes with a false discovery rate less than 0.1 were considered. We observed a significant activation of toll-like-receptor signalling and gamma-delta T cells, angiogenesis, and the integrin pathway in PG compared to non-involved skin. Induced modules network analysis of the 500 most significantly differentially expression genes revealed that STAT3 as well as genes regulating cell cycle (CCND1, CDKN1A) and cell death (BCL2) are hub genes in the molecular signature of PG. Hence, transcriptome of PG is composed of an upregulation of innate immunity, cell cycle and regulated cell death. These data might be useful to define future treatment approaches of PG.

Published
2017

50. T-Zellantwort bei der Autoimmunpankreatitis: Vergleichende Analyse der T-Zellsubpopulationen unter besonderer Berücksichtigung der Th17-Zellantwort

Author

Lauffer, Felix Josef, Kleeff, Jörg H. (Prof. Dr.), and Algül, Hana (Priv.-Doz. Dr.)

Subjects
Medizin und Gesundheit, Autoimmunpankreatitis, Th17-Zellen, ddc:610, autoimmune pancreatitis, Th17 cells
Abstract

Autoimmunpankreatitis (AIP) ist eine seltene Form der chronischen Pankreatitis, von der mindestens zwei Subtypen existieren: AIP Typ I zeichnet sich durch eine starke Invasion IgG4-positiver Plasmazellen, AIP Typ II durch granulozytäre Läsionen der Gangepithelien aus. In einer Genexpressionsanalyse wurden erstmalig Th17-Zellen bei der AIP nachgewiesen. Immunhistochemische Färbungen zeigten bei der AIP Typ II periduktal signifikant mehr IL-17A/CD4-positive Zellen und neutrophile Granulozyten als bei der AIP Typ I. Diese Ergebnisse ermöglichen neue Forschungs-, und Therapiemöglichkeiten der AIP. Autoimmune pancreatitis (AIP) is a rare form of chronic pancreatitis. There are at least two subtypes: AIP type I with an invasion of IgG4-positive plasma cells and AIP type II characterized by granulocyte epithelial lesions. We investigated T cell populations in AIP using a gene expression analysis. For the first time, Th17 cells could be detected in AIP tissue. Immunohistochemistry showed a significantly higher amount of IL-17A/CD4-positive cells and neutrophil granulocytes in periductal areas of AIP type II compared to type I. These results allow new scientific and therapeutic approaches.

Published
2014

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