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2. European and multi-ancestry genome-wide association meta-analysis of atopic dermatitis highlights importance of systemic immune regulation

Author

Budu-Aggrey, Ashley, Kilanowski, Anna, Sobczyk, Maria K., Shringarpure, Suyash S., Mitchell, Ruth, Reis, Kadri, Reigo, Anu, Mägi, Reedik, Nelis, Mari, Tanaka, Nao, Brumpton, Ben M., Thomas, Laurent F., Sole-Navais, Pol, Flatley, Christopher, Espuela-Ortiz, Antonio, Herrera-Luis, Esther, Lominchar, Jesus V. T., Bork-Jensen, Jette, Marenholz, Ingo, Arnau-Soler, Aleix, Jeong, Ayoung, Fawcett, Katherine A., Baurecht, Hansjorg, Rodriguez, Elke, Alves, Alexessander Couto, Kumar, Ashish, Sleiman, Patrick M., Chang, Xiao, Medina-Gomez, Carolina, Hu, Chen, Xu, Cheng-jian, Qi, Cancan, El-Heis, Sarah, Titcombe, Philip, Antoun, Elie, Fadista, João, Wang, Carol A., Thiering, Elisabeth, Wu, Baojun, Kress, Sara, Kothalawala, Dilini M., Kadalayil, Latha, Duan, Jiasong, Zhang, Hongmei, Hadebe, Sabelo, Hoffmann, Thomas, Jorgenson, Eric, Choquet, Hélène, Risch, Neil, Njølstad, Pål, Andreassen, Ole A., Johansson, Stefan, Almqvist, Catarina, Gong, Tong, Ullemar, Vilhelmina, Karlsson, Robert, Magnusson, Patrik K. E., Szwajda, Agnieszka, Burchard, Esteban G., Thyssen, Jacob P., Hansen, Torben, Kårhus, Line L., Dantoft, Thomas M., Jeanrenaud, Alexander C.S.N., Ghauri, Ahla, Arnold, Andreas, Homuth, Georg, Lau, Susanne, Nöthen, Markus M., Hübner, Norbert, Imboden, Medea, Visconti, Alessia, Falchi, Mario, Bataille, Veronique, Hysi, Pirro, Ballardini, Natalia, Boomsma, Dorret I., Hottenga, Jouke J., Müller-Nurasyid, Martina, Ahluwalia, Tarunveer S., Stokholm, Jakob, Chawes, Bo, Schoos, Ann-Marie M., Esplugues, Ana, Bustamante, Mariona, Raby, Benjamin, Arshad, Syed, German, Chris, Esko, Tõnu, Milani, Lili A., Metspalu, Andres, Terao, Chikashi, Abuabara, Katrina, Løset, Mari, Hveem, Kristian, Jacobsson, Bo, Pino-Yanes, Maria, Strachan, David P., Grarup, Niels, Linneberg, Allan, Lee, Young-Ae, Probst-Hensch, Nicole, Weidinger, Stephan, Jarvelin, Marjo-Riitta, Melén, Erik, Hakonarson, Hakon, Irvine, Alan D., Jarvis, Deborah, Nijsten, Tamar, Duijts, Liesbeth, Vonk, Judith M., Koppelmann, Gerard H., Godfrey, Keith M., Barton, Sheila J., Feenstra, Bjarke, Pennell, Craig E., Sly, Peter D., Holt, Patrick G., Williams, L. Keoki, Bisgaard, Hans, Bønnelykke, Klaus, Curtin, John, Simpson, Angela, Murray, Clare, Schikowski, Tamara, Bunyavanich, Supinda, Weiss, Scott T., Holloway, John W., Min, Josine L., Brown, Sara J., Standl, Marie, and Paternoster, Lavinia

Published
2023
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3. Progression of acute-to-chronic atopic dermatitis is associated with quantitative rather than qualitative changes in cytokine responses

Author

Tsoi, Lam C, Rodriguez, Elke, Stölzl, Dora, Wehkamp, Ulrike, Sun, Jingru, Gerdes, Sascha, Sarkar, Mrinal K, Hübenthal, Matthias, Zeng, Chang, Uppala, Ranjitha, Xing, Xianying, Thielking, Frederieke, Billi, Allison C, Swindell, William R, Shefler, Alanna, Chen, Jiahan, Patrick, Matthew T, Harms, Paul W, Kahlenberg, J Michelle, Perez White, Bethany E, Maverakis, Emanual, Gudjonsson, Johann E, and Weidinger, Stephan

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Eczema / Atopic Dermatitis, Clinical Research, Genetics, Aetiology, 2.1 Biological and endogenous factors, Inflammatory and immune system, Skin, Acute Disease, Chronic Disease, Cytokines, Dermatitis, Atopic, Female, Humans, Male, Sequence Analysis, RNA, Th1 Cells, Th17 Cells, Th2 Cells, Transcriptome, Atopic dermatitis, RNA-sequencing, nonlesional, chronic AD, acute AD, Immunology, Allergy
Abstract

BackgroundAlthough multiple studies have assessed molecular changes in chronic atopic dermatitis (AD) lesions, little is known about the transition from acute to chronic disease stages, and the factors and mechanisms that shape chronic inflammatory activity.ObjectivesWe sought to assess the global transcriptome changes that characterize the progression from acute to chronic stages of AD.MethodsWe analyzed transcriptome changes in paired nonlesional skin, acute and chronic AD lesions from 11 patients and 38 healthy controls by RNA-sequencing, and conducted in vivo and histological assays to evaluate findings.ResultsOur data demonstrate that approximately 74% of the genes dysregulated in acute lesions remain or are further dysregulated in chronic lesions, whereas only 34% of the genes dysregulated in chronic lesions are altered already in the acute stage. Nonlesional AD skin exhibited enrichment of TNF, TH1, TH2, and TH17 response genes. Acute lesions showed marked dendritic-cell signatures and a prominent enrichment of TH1, TH2, and TH17 responses, along with increased IL-36 and thymic stromal lymphopoietin expression, which were further heightened in chronic lesions. In addition, genes involved in skin barrier repair, keratinocyte proliferation, wound healing, and negative regulation of T-cell activation showed a significant dysregulation in the chronic versus acute comparison. Furthermore, our data show progressive changes in vasculature and maturation of dendritic-cell subsets with chronicity, with FOXK1 acting as immune regulator.ConclusionsOur results show that the changes accompanying the transition from nonlesional to acute to chronic inflammation in AD are quantitative rather than qualitative, with chronic AD having heightened TH2, TH1, TH17, and IL36 responses and skin barrier repair mechanisms. These findings provide novel insights and highlight underappreciated pathways in AD pathogenesis that may be amenable to therapeutic targeting.

Published
2020

5. Atopic Dermatitis Is an IL-13–Dominant Disease with Greater Molecular Heterogeneity Compared to Psoriasis

Author

Tsoi, Lam C, Rodriguez, Elke, Degenhardt, Frauke, Baurecht, Hansjörg, Wehkamp, Ulrike, Volks, Natalie, Szymczak, Silke, Swindell, William R, Sarkar, Mrinal K, Raja, Kalpana, Shao, Shuai, Patrick, Matthew, Gao, Yilin, Uppala, Ranjitha, Perez White, Bethany E, Getsios, Spiro, Harms, Paul W, Maverakis, Emanual, Elder, James T, Franke, Andre, Gudjonsson, Johann E, and Weidinger, Stephan

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Psoriasis, Autoimmune Disease, Eczema / Atopic Dermatitis, Human Genome, Genetics, Biotechnology, 2.1 Biological and endogenous factors, Aetiology, Skin, Good Health and Well Being, Cohort Studies, Dermatitis, Atopic, Gene Expression Profiling, Humans, Interleukin-13, Interleukin-4, Organ Specificity, RNA, RNA, Long Noncoding, Sequence Analysis, RNA, Signal Transduction, Th2 Cells, Transcriptome, Oncology and Carcinogenesis, Dermatology & Venereal Diseases, Clinical sciences
Abstract

Atopic dermatitis (AD) affects up to 20% of children and adults worldwide. To gain a deeper understanding of the pathophysiology of AD, we conducted a large-scale transcriptomic study of AD with deeply sequenced RNA-sequencing samples using long (126-bp) paired-end reads. In addition to the comparisons against previous transcriptomic studies, we conducted in-depth analysis to obtain a high-resolution view of the global architecture of the AD transcriptome and contrasted it with that of psoriasis from the same cohort. By using 147 RNA samples in total, we found striking correlation between dysregulated genes in lesional psoriasis and lesional AD skin with 81% of AD dysregulated genes being shared with psoriasis. However, we described disease-specific molecular and cellular features, with AD skin showing dominance of IL-13 pathways, but with near undetectable IL-4 expression. We also demonstrated greater disease heterogeneity and larger proportion of dysregulated long noncoding RNAs in AD, and illustrated the translational impact, including skin-type classification and drug-target prediction. This study is by far the largest study comparing the AD and psoriasis transcriptomes using RNA sequencing and demonstrating the shared inflammatory components, as well as specific discordant cytokine signatures of these two skin diseases.

Published
2019

6. Influence of FLG loss-of-function mutations in host–microbe interactions during atopic skin inflammation

Author

Oláh, Peter, Szlávicz, Eszter, Kuchner, Marcus, Nemmer, Jana, Zeeuwen, Patrick, Lefèvre-Utile, Alain, Fyhrquist, Nanna, Prast-Nielsen, Stefanie, Skoog, Tiina, Serra, Angela, Rodríguez, Elke, Raap, Ulrike, Meller, Stephan, Gyulai, Rolland, Hupé, Philippe, Kere, Juha, Levi-Schaffer, Francesca, Tsoka, Sophia, Alexander, Helen, Nestle, Frank O., Schröder, Jens M., Weidinger, Stephan, van den Bogaard, Ellen, Soumelis, Vassili, Greco, Dario, Barker, Jonathan, Lauerma, Antti, Ranki, Annamari, Andersson, Björn, Alenius, Harri, and Homey, Bernhard

Published
2022
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7. Host genetic factors related to innate immunity, environmental sensing and cellular functions are associated with human skin microbiota

Author

Moitinho-Silva, Lucas, Degenhardt, Frauke, Rodriguez, Elke, Emmert, Hila, Juzenas, Simonas, Möbus, Lena, Uellendahl-Werth, Florian, Sander, Nicole, Baurecht, Hansjörg, Tittmann, Lukas, Lieb, Wolfgang, Gieger, Christian, Peters, Annette, Ellinghaus, David, Bang, Corinna, Franke, Andre, Weidinger, Stephan, and Rühlemann, Malte Christoph

Published
2022
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9. Blockade of interleukin-13 signalling improves skin barrier function and biology in patients with moderate-to-severe atopic dermatitis.

Author

Sander, Nicole, Stölzl, Dora, Fonfara, Melina, Hartmann, Jan, Harder, Inken, Suhrkamp, Ina, Jakaša, Ivone, van den Bogaard, Ellen, Vlijmen-Willems, Ivonne van, Szymczak, Silke, Rodriguez, Elke, Gerdes, Sascha, and Weidinger, Stephan

Subjects
SKIN physiology, ATOPIC dermatitis, INTERLEUKIN-13, STAPHYLOCOCCUS aureus, BIOLOGY
Abstract

Background Interleukin (IL)-13 is a key driver of inflammation and barrier dysfunction in atopic dermatitis (AD). While there is robust evidence that tralokinumab – a monoclonal antibody that neutralizes IL-13 – reduces inflammation and clinical disease activity, less is known about its effects on barrier function. Objectives To characterize the effects of tralokinumab treatment on skin barrier function. Methods Transepidermal water loss (TEWL), stratum corneum hydration (SCH), natural moisturizing factor content, histopathological characteristics, biomarker expression and microbiome composition were evaluated in lesional, nonlesional and sodium lauryl sulfate-irritated skin of 16 patients with AD over the course of 16 weeks of tralokinumab treatment. Results All clinical severity scores decreased significantly over time. At week 16, mean TEWL in target lesions decreased by 33% (P = 0.01) and SCH increased by 58% (P = 0.004), along with a histological reduction in spongiosis (P = 0.003), keratin 16 expression and epidermal thickness (P = 0.001). In parallel, there was a significant decrease in several barrier dysfunction-associated and proinflammatory proteins such as fibronectin (P = 0.006), CCL17/TARC (P = 0.03) and IL-8 (P = 0.01), with significant changes seen as early as week 8. Total bacterial load and Staphylococcus aureus abundance were significantly reduced from week 2. Conclusions Tralokinumab treatment improved skin physiology, epidermal pathology and dysbiosis, further highlighting the pleiotropic role of IL-13 in AD pathogenesis. [ABSTRACT FROM AUTHOR]

Published
2024
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10. Stratum corneum and microbial biomarkers precede and characterize childhood atopic dermatitis.

Author

Fonfara, Melina, Hartmann, Jan, Stölzl, Dora, Sander, Nicole, Harder, Inken, Rodriguez, Elke, Hübenthal, Matthias, Mazur, Carsten, Kerzel, Sebastian, Kabesch, Michael, Schmitt, Jochen, Emmert, Hila, Suhrkamp, Ina, and Weidinger, Stephan

Subjects
STAPHYLOCOCCUS epidermidis, ATOPIC dermatitis, RANDOMIZED controlled trials, NATURAL immunity, SKIN diseases
Abstract

Background: Atopic dermatitis (AD) is the most common paediatric inflammatory skin disease. There are currently no robust biomarkers that could reliably predict its manifestation, and on the molecular level, it is less well characterized than adult AD. Objectives: This study aimed to extend previous findings and provide evidence for distinct changes of the epidermal proteome and microbiome preceding the onset of AD as well as characterizing early AD. Methods: We longitudinally analysed epidermal biomarker levels and microbial profiles in a cohort of 50 neonates at high risk for AD, who had participated in a randomized controlled trial on early emollient use for AD prevention. Results: About 26% of the infants developed AD until month 24 with an average age of 10 month at disease onset. In children with later AD, IL‐1Ra, TNFβ, IL‐8, IL‐18, IL‐22, CCL2, TARC, TSLP and VEGFa showed increased levels prior to disease manifestation with levels of IL‐1Ra, TNFβ and VEGFa already increased shortly after birth. Further, children with later AD displayed a delayed maturation and differentially composed skin microbiome prior to AD onset. At manifestation, levels of multiple Th2, Th17/22 and Th1‐associated biomarkers as well as innate immunity markers were elevated, and abundances of commensal Streptococcus species were reduced in favour of Staphylococcus epidermidis. Conclusions: Our results indicate that elevations of proinflammatory stratum corneum biomarkers and alterations of the skin microbiome precede paediatric AD and characterize the disease at onset. [ABSTRACT FROM AUTHOR]

Published
2024
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11. Protein-coding variants contribute to the risk of atopic dermatitis and skin-specific gene expression

Author

Mucha, Sören, Baurecht, Hansjörg, Novak, Natalija, Rodríguez, Elke, Bej, Saptarshi, Mayr, Gabriele, Emmert, Hila, Stölzl, Dora, Gerdes, Sascha, Jung, Eun Suk, Degenhardt, Frauke, Hübenthal, Matthias, Ellinghaus, Eva, Kässens, Jan Christian, Wienbrandt, Lars, Lieb, Wolfgang, Müller-Nurasyid, Martina, Hotze, Melanie, Dand, Nick, Grosche, Sarah, Marenholz, Ingo, Arnold, Andreas, Homuth, Georg, Schmidt, Carsten O., Wehkamp, Ulrike, Nöthen, Markus M., Hoffmann, Per, Paternoster, Lavinia, Standl, Marie, Bønnelykke, Klaus, Ahluwalia, Tarunveer S., Bisgaard, Hans, Peters, Annette, Gieger, Christian, Waldenberger, Melanie, Schulz, Holger, Strauch, Konstantin, Werfel, Thomas, Lee, Young-Ae, Wolfien, Markus, Rosenstiel, Philip, Wolkenhauer, Olaf, Schreiber, Stefan, Franke, Andre, Weidinger, Stephan, and Ellinghaus, David

Published
2020
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12. Rare variant analysis in eczema identifies exonic variants in DUSP1, NOTCH4 and SLC9A4

Author

Grosche, Sarah, Marenholz, Ingo, Esparza-Gordillo, Jorge, Arnau-Soler, Aleix, Pairo-Castineira, Erola, Rüschendorf, Franz, Ahluwalia, Tarunveer S., Almqvist, Catarina, Arnold, Andreas, Baurecht, Hansjörg, Bisgaard, Hans, Bønnelykke, Klaus, Brown, Sara J., Bustamante, Mariona, Curtin, John A., Custovic, Adnan, Dharmage, Shyamali C., Esplugues, Ana, Falchi, Mario, Fernandez-Orth, Dietmar, Ferreira, Manuel A. R., Franke, Andre, Gerdes, Sascha, Gieger, Christian, Hakonarson, Hakon, Holt, Patrick G., Homuth, Georg, Hubner, Norbert, Hysi, Pirro G., Jarvelin, Marjo-Riitta, Karlsson, Robert, Koppelman, Gerard H., Lau, Susanne, Lutz, Manuel, Magnusson, Patrik K. E., Marks, Guy B., Müller-Nurasyid, Martina, Nöthen, Markus M., Paternoster, Lavinia, Pennell, Craig E., Peters, Annette, Rawlik, Konrad, Robertson, Colin F., Rodriguez, Elke, Sebert, Sylvain, Simpson, Angela, Sleiman, Patrick M. A., Standl, Marie, Stölzl, Dora, Strauch, Konstantin, Szwajda, Agnieszka, Tenesa, Albert, Thompson, Philip J., Ullemar, Vilhelmina, Visconti, Alessia, Vonk, Judith M., Wang, Carol A., Weidinger, Stephan, Wielscher, Matthias, Worth, Catherine L., Xu, Chen-Jian, and Lee, Young-Ae

Published
2021
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14. Inhibition of RNase 7 by RNase inhibitor promotes inflammation and Staphylococcus aureus growth: Implications for atopic dermatitis.

Author

Rademacher, Franziska, Scheel, Annika, Gläser, Regine, Schröder, Lena, Heinemann, Nina, Bartels, Joachim, Gerdes, Sascha, Stölzl, Dora, Rodriguez, Elke, Döhner, Katinka, Weidinger, Stephan, Werfel, Thomas, and Harder, Jürgen

Subjects
ATOPIC dermatitis, STAPHYLOCOCCUS aureus, AD blockers, INFLAMMATION, RIBONUCLEASES
Abstract

Background: The antimicrobial ribonuclease RNase 7 is abundantly expressed in the epidermis of lesional skin of atopic dermatitis (AD). Host RNase inhibitor (RI) binds to RNase 7 and blocks its ribonuclease activity. This study aimed to evaluate the impact of RNase 7–RI interactions on AD. Methods: Cultured human primary keratinocytes, with siRNA‐mediated downregulation of RNase 7 and RI, were stimulated with the synthetic RNA polyinosinic‐polycytidylic acid (poly I:C). Induction of proinflammatory mediators was analyzed by real‐time PCR and ELISA. RI expression in AD non‐lesional and lesional skin biopsies and healthy controls was analyzed by real‐time PCR and immunostaining. RI protein release in vivo on the AD skin surface was determined by western blot. Antimicrobial and ribonuclease assays were used to investigate the functional role of RI. Results: RNase 7 inhibited the RNA‐induced expression of proinflammatory mediators in keratinocytes. Accordingly, downregulation of RNase 7 in keratinocytes enhanced RNA‐mediated induction of proinflammatory mediators, whereas downregulation of RI had the opposite effect. RI was released by damaged keratinocytes and epidermis. In vivo expression and release of RI on the skin surface were enhanced in lesional AD skin. Rinsing solution from the surface of lesional AD skin blocked the ribonuclease activity of RNase 7. The anti‐Staphylococcus aureus activity of RNase 7 was abrogated by RI. Conclusions: Our data suggest a novel role of RI as a trigger factor of inflammation in AD by blocking the ribonuclease and antimicrobial activity of RNase 7, thereby enhancing RNA‐mediated inflammation and S. aureus growth. [ABSTRACT FROM AUTHOR]

Published
2024
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16. miR-146b Probably Assists miRNA-146a in the Suppression of Keratinocyte Proliferation and Inflammatory Responses in Psoriasis

Author

Hermann, Helen, Runnel, Toomas, Aab, Alar, Baurecht, Hansjörg, Rodriguez, Elke, Magilnick, Nathaniel, Urgard, Egon, Šahmatova, Liisi, Prans, Ele, Maslovskaja, Julia, Abram, Kristi, Karelson, Maire, Kaldvee, Bret, Reemann, Paula, Haljasorg, Uku, Rückert, Beate, Wawrzyniak, Paulina, Weichenthal, Michael, Mrowietz, Ulrich, Franke, Andre, Gieger, Christian, Barker, Jonathan, Trembath, Richard, Tsoi, Lam C., Elder, James T., Tkaczyk, Eric R., Kisand, Kai, Peterson, Pärt, Kingo, Külli, Boldin, Mark, Weidinger, Stephan, Akdis, Cezmi A., and Rebane, Ana

Published
2017
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17. Association of Atopic Dermatitis with Cardiovascular Risk Factors and Diseases

Author

Standl, Marie, Tesch, Falko, Baurecht, Hansjörg, Rodríguez, Elke, Müller-Nurasyid, Martina, Gieger, Christian, Peters, Annette, Wang-Sattler, Rui, Prehn, Cornelia, Adamski, Jerzy, Kronenberg, Florian, Schulz, Holger, Koletzko, Sibylle, Schikowski, Tamara, von Berg, Andrea, Lehmann, Irina, Berdel, Dietrich, Heinrich, Joachim, Schmitt, Jochen, and Weidinger, Stephan

Published
2017
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19. Effects of Early Emollient Use in Children at High Risk of Atopic Dermatitis: A German Pilot Study

Author

Harder, Inken, primary, Stölzl, Dora, additional, Sander, Nicole, additional, Hartmann, Jan, additional, Rodriguez, Elke, additional, Mazur, Carsten, additional, Kerzel, Sebastian, additional, Kabesch, Michael, additional, Küster, Denise, additional, Schmitt, Jochen, additional, Fölster-Holst, Regina, additional, Gerdes, Sascha, additional, Emmert, Hila, additional, and Weidinger, Stephan, additional

Published
2023
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20. Atopic dermatitis is associated with an increased risk for rheumatoid arthritis and inflammatory bowel disease, and a decreased risk for type 1 diabetes

Author

Schmitt, Jochen, Schwarz, Kristin, Baurecht, Hansjörg, Hotze, Melanie, Fölster-Holst, Regina, Rodríguez, Elke, Lee, Young A.E., Franke, Andre, Degenhardt, Frauke, Lieb, Wolfgang, Gieger, Christian, Kabesch, Michael, Nöthen, Markus M., Irvine, Alan D., McLean, W.H. Irwin, Deckert, Stefanie, Stephan, Victoria, Schwarz, Peter, Aringer, Martin, Novak, Natalija, and Weidinger, Stephan

Published
2016
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21. Effects of cultured keratinocyte‐ and fibroblast‐derived mediators on three‐dimensional skin models.

Author

Fonfara, Melina, Brodersen, Carina, Suhrkamp, Ina, Rodriguez, Elke, Weidinger, Stephan, and Emmert, Hila

Subjects
THREE-dimensional modeling, SKIN proteins, CYTOSKELETAL proteins, PATHOLOGICAL physiology, ARYL hydrocarbon receptors
Abstract

This article discusses the effects of keratinocyte- and fibroblast-derived factors on three-dimensional (3D) skin models, specifically focusing on epidermal organization and barrier marker expression. The study found that keratinocytes secrete pro-inflammatory mediators that can cause disease-associated patterns in the skin models. The researchers also observed that blocking IL-4Rα, a receptor involved in immune dysfunction, only partially improved the skin barrier, suggesting that other factors play a role in skin inflammation. Overall, the findings highlight the contribution of keratinocyte-derived cytokines to skin barrier dysfunction and the importance of understanding their role in conditions like atopic dermatitis. [Extracted from the article]

Published
2024
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22. Dupilumab but not cyclosporine treatment shifts the microbiome toward a healthy skin flora in patients with moderate‐to‐severe atopic dermatitis.

Author

Hartmann, Jan, Moitinho‐Silva, Lucas, Sander, Nicole, Harder, Inken, Häsler, Robert, Rodriguez, Elke, Haufe, Eva, Kleinheinz, Andreas, Abraham, Susanne, Heratizadeh, Annice, Weisshaar, Elke, Schäkel, Knut, Handrick, Christiane, Augustin, Matthias, Wollenberg, Andreas, Staubach‐Renz, Petra, Ertner, Konstantin, Sticherling, Michael, Schwarz, Beate, and Quist, Sven

Subjects
ATOPIC dermatitis, DUPILUMAB, CYCLOSPORINE, BOTANY, BACTERIAL diversity, ECZEMA
Abstract

Background: Atopic dermatitis (AD) patients display an altered skin microbiome which may not only be an indicator but also a driver of inflammation. We aimed to investigate associations among AD patients' skin microbiome, clinical data, and response to systemic therapy in patients of the TREATgermany registry. Methods: Skin swabs of 157 patients were profiled with 16S rRNA gene amplicon sequencing before and after 3 months of treatment with dupilumab or cyclosporine. For comparison, 16s microbiome data from 258 population‐based healthy controls were used. Disease severity was assessed using established instruments such as the Eczema Area and Severity Index (EASI). Results: We confirmed the previously shown correlation of Staphylococcus aureus abundance and bacterial alpha diversity with AD severity as measured by EASI. Therapy with Dupilumab shifted the bacterial community toward the pattern seen in healthy controls. The relative abundance of Staphylococci and in particular S. aureus significantly decreased on both lesional and non‐lesional skin, whereas the abundance of Staphylococcus hominis increased. These changes were largely independent from the degree of clinical improvement and were not observed for cyclosporine. Conclusions: Systemic treatment with dupilumab but not cyclosporine tends to restore a healthy skin microbiome largely independent of the clinical response indicating potential effects of IL‐4RA blockade on the microbiome. [ABSTRACT FROM AUTHOR]

Published
2023
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26. Blood transcriptome profiling identifies 2 candidate endotypes of atopic dermatitis

Author

Möbus, Lena, primary, Rodriguez, Elke, additional, Harder, Inken, additional, Boraczynski, Nicole, additional, Szymczak, Silke, additional, Hübenthal, Matthias, additional, Stölzl, Dora, additional, Gerdes, Sascha, additional, Kleinheinz, Andreas, additional, Abraham, Susanne, additional, Heratizadeh, Annice, additional, Handrick, Christiane, additional, Haufe, Eva, additional, Werfel, Thomas, additional, Schmitt, Jochen, additional, and Weidinger, Stephan, additional

Published
2022
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28. Exome-wide association study reveals novel psoriasis susceptibility locus at TNFSF15 and rare protective alleles in genes contributing to type I IFN signalling

Author

Dand, Nick, Mucha, Sören, Tsoi, Lam C, Mahil, Satveer K, Stuart, Philip E, Arnold, Andreas, Baurecht, Hansjörg, Burden, A David, Callis Duffin, Kristina, Chandran, Vinod, Curtis, Charles J, Das, Sayantan, Ellinghaus, David, Ellinghaus, Eva, Enerback, Charlotta, Esko, Tõnu, Gladman, Dafna D, Griffiths, Christopher E M, Gudjonsson, Johann E, Hoffman, Per, Homuth, Georg, Hüffmeier, Ulrike, Krueger, Gerald G, Laudes, Matthias, Lee, Sang Hyuck, Lieb, Wolfgang, Lim, Henry W, Löhr, Sabine, Mrowietz, Ulrich, Müller-Nurayid, Martina, Nöthen, Markus, Peters, Annette, Rahman, Proton, Reis, André, Reynolds, Nick J, Rodriguez, Elke, Schmidt, Carsten O, Spain, Sarah L, Strauch, Konstantin, Tejasvi, Trilokraj, Voorhees, John J, Warren, Richard B, Weichenthal, Michael, Weidinger, Stephan, Zawistowski, Matthew, Nair, Rajan P, Capon, Francesca, Smith, Catherine H, Trembath, Richard C, Abecasis, Goncalo R, Elder, James T, Franke, Andre, Simpson, Michael A, and Barker, Jonathan N

Published
2017
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29. A comprehensive analysis of the COL29A1 gene does not support a role in eczema

Author

Naumann, Aline, Söderhäll, Cilla, Fölster-Holst, Regina, Baurecht, Hansjörg, Harde, Viola, Müller-Wehling, Konstanze, Rodríguez, Elke, Ruether, Andreas, Franke, Andre, Wagenpfeil, Stefan, Novak, Natalija, Mempel, Martin, Kalali, Behnam Naderi, Allgaeuer, Michael, Koch, Jeanette, Gerhard, Markus, Melén, Erik, Wahlgren, Carl-Fredrik, Kull, Inger, Stahl, Caroline, Pershagen, Göran, Lauener, Roger, Riedler, Josef, Doekes, Gert, Scheynius, Annika, Illig, Thomas, von Mutius, Erika, Schreiber, Stefan, Kere, Juha, Kabesch, Michael, and Weidinger, Stephan

Published
2011
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30. The power and potential of BIOMAP to elucidate host-microbiome interplay in skin inflammatory diseases

Author

Alenius, Harri, Sinkko, Hanna, Moitinho-Silva, Lucas, Rodriguez, Elke, Broderick, Conor, Alexander, Helen, Reiger, Matthias, Hjelmsø, Mathis Hjort, Fyhrquist, Nanna, Olah, Peter, Bryce, Paul, Smith, Catherine, Koning, Frits, Eyerich, Kilian, Greco, Dario, van den Bogaard, Ellen H., Neumann, Avidan U., Traidl-Hoffmann, Claudia, Homey, Bernhard, Flohr, Carsten, Bønnelykke, Klaus, Stokholm, Jakob, Weidinger, Stephan, HUMI - Human Microbiome Research, Faculty of Medicine, Institute of Biotechnology, Helsinki Institute of Life Science HiLIFE, Tampere University, and BioMediTech

Subjects
atopic dermatitis, STAPHYLOCOCCUS-AUREUS COLONIZATION, GUT MICROBIOTA, biomarkers, microbiome, ECZEMA, psoriasis, YOUNG INFANT, ASSOCIATION, GLOBAL BURDEN, PREVALENCE, EARLY-LIFE, 3121 General medicine, internal medicine and other clinical medicine, CHRONIC PLAQUE PSORIASIS, ATOPIC-DERMATITIS, 3111 Biomedicine
Abstract

The two most common chronic inflammatory skin diseases are atopic dermatitis (AD) and psoriasis. The underpinnings of the remarkable degree of clinical heterogeneity of AD and psoriasis are poorly understood and, as a consequence, disease onset and progression are unpredictable and the optimal type and time point for intervention are as yet unknown. The BIOMAP project is the first IMI (Innovative Medicines Initiative) project dedicated to investigating the causes and mechanisms of AD and psoriasis and to identify potential biomarkers responsible for the variation in disease outcome. The consortium includes 7 large pharmaceutical companies and 25 non-industry partners including academia. Since there is mounting evidence supporting an important role for microbial exposures and our microbiota as factors mediating immune polarization and AD and psoriasis pathogenesis, an entire work package is dedicated to the investigation of skin and gut microbiome linked to AD or psoriasis. The large collaborative BIOMAP project will enable the integration of patient cohorts, data and knowledge in unprecedented proportions. The project has a unique opportunity with a potential to bridge and fill the gaps between current problems and solutions. This review highlights the power and potential of the BIOMAP project in the investigation of microbe-host interplay in AD and psoriasis. publishedVersion

Published
2021

31. Comparison of Epidermal Barrier Integrity in Adults with Classic Atopic Dermatitis, Atopic Prurigo and Non-Atopic Prurigo Nodularis

Author

Fölster-Holst, Regina, primary, Reimer, Rahel, additional, Neumann, Claudia, additional, Proksch, Erhardt, additional, Rodriguez, Elke, additional, Weidinger, Stephan, additional, Goldust, Mohamad, additional, Hanisch, Eckhard, additional, Dähnhardt-Pfeiffer, Stephan, additional, and Freitag-Wolf, Sandra, additional

Published
2021
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32. The power and potential of BIOMAP to elucidate host‐microbiome interplay in skin inflammatory diseases

Author

Alenius, Harri, primary, Sinkko, Hanna, additional, Moitinho‐Silva, Lucas, additional, Rodriguez, Elke, additional, Broderick, Conor, additional, Alexander, Helen, additional, Reiger, Matthias, additional, Hjelmsø, Mathis Hjort, additional, Fyhrquist, Nanna, additional, Olah, Peter, additional, Bryce, Paul, additional, Smith, Catherine, additional, Koning, Frits, additional, Eyerich, Kilian, additional, Greco, Dario, additional, Bogaard, Ellen H., additional, Neumann, Avidan U., additional, Traidl‐Hoffmann, Claudia, additional, Homey, Bernhard, additional, Flohr, Carsten, additional, Bønnelykke, Klaus, additional, Stokholm, Jakob, additional, and Weidinger, Stephan, additional

Published
2021
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33. Elevated NK-cell transcriptional signature and dysbalance of resting and activated NK cells in atopic dermatitis

Author

Möbus, Lena, primary, Rodriguez, Elke, additional, Harder, Inken, additional, Schwarz, Agatha, additional, Wehkamp, Ulrike, additional, Stölzl, Dora, additional, Boraczynski, Nicole, additional, Gerdes, Sascha, additional, Litman, Thomas, additional, Kleinheinz, Andreas, additional, Abraham, Susanne, additional, Heratizadeh, Annice, additional, Handrick, Christiane, additional, Haufe, Eva, additional, Schmitt, Jochen, additional, Werfel, Thomas, additional, and Weidinger, Stephan, additional

Published
2021
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34. Atopic dermatitis displays stable and dynamic skin transcriptome signatures

Author

Möbus, Lena, primary, Rodriguez, Elke, additional, Harder, Inken, additional, Stölzl, Dora, additional, Boraczynski, Nicole, additional, Gerdes, Sascha, additional, Kleinheinz, Andreas, additional, Abraham, Susanne, additional, Heratizadeh, Annice, additional, Handrick, Christiane, additional, Haufe, Eva, additional, Werfel, Thomas, additional, Schmitt, Jochen, additional, and Weidinger, Stephan, additional

Published
2021
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35. A genome-wide association study of atopic dermatitis identifies loci with overlapping effects on asthma and psoriasis

Author

Weidinger, Stephan, Willis-Owen, Saffron A.G., Kamatani, Yoichiro, Baurecht, Hansjörg, Morar, Nilesh, Liang, Liming, Edser, Pauline, Street, Teresa, Rodriguez, Elke, OʼRegan, Grainne M., Beattie, Paula, Fölster-Holst, Regina, Franke, Andre, Novak, Natalija, Fahy, Caoimhe M., Winge, Mårten C.G., Kabesch, Michael, Illig, Thomas, Heath, Simon, Söderhäll, Cilla, Melén, Erik, Pershagen, Göran, Kere, Juha, Bradley, Maria, Lieden, Agne, Nordenskjold, Magnus, Harper, John I., Mclean, W.H. Irwin, Brown, Sara J., Cookson, William O.C., Lathrop, G. Mark, Irvine, Alan D., and Moffatt, Miriam F.

Published
2013
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37. Loss-of-function variations within the filaggrin gene predispose for atopic dermatitis with allergic sensitizations

Author

Weidinger, Stephan, Illig, Thomas, Baurecht, Hansjörg, Irvine, Alan D., Rodriguez, Elke, Diaz-Lacava, Amalia, Klopp, Norman, Wagenpfeil, Stefan, Zhao, Yiwei, Liao, Haihui, Lee, Simon P., Palmer, Colin N.A., Jenneck, Claudia, Maintz, Laura, Hagemann, Tobias, Behrendt, Heidrun, Ring, Johannes, Nothen, Markus M., McLean, W. H. Irwin, and Novak, Natalija

Published
2006
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41. 46th annual congress of the Arbeitsgemeinschaft Dermatologische Forschung in Munich, Germany

Author

Gaffal, Evelyn, Eming, Ruediger, Fabri, Mario, Gebhardt, Christoffer, Stary, Georg, Eyerich, Stefanie, Hoelzel, Michael, Kosnopfel, Corinna, Neubert, Elsa, Rauer, Denise, Rodriguez, Elke, Thiem, Alexander, von Meyenn, Leonhard, Buhl, Timo, Gaffal, Evelyn, Eming, Ruediger, Fabri, Mario, Gebhardt, Christoffer, Stary, Georg, Eyerich, Stefanie, Hoelzel, Michael, Kosnopfel, Corinna, Neubert, Elsa, Rauer, Denise, Rodriguez, Elke, Thiem, Alexander, von Meyenn, Leonhard, and Buhl, Timo

Published
2019

42. Stratum corneum lipidomics analysis reveals altered ceramide profile in atopic dermatitis patients across body sites with correlated changes in skin microbiome.

Author

Emmert, Hila, Baurecht, Hansjörg, Thielking, Frederieke, Stölzl, Dora, Rodriguez, Elke, Harder, Inken, Proksch, Ehrhardt, and Weidinger, Stephan

Subjects
CERAMIDES, ATOPIC dermatitis, BACTERIAL colonies, SKIN physiology, ADULTS
Abstract

Background: Atopic dermatitis (AD) is driven by the interplay between a dysfunctional epidermal barrier and a skewed cutaneous immune dysregulation. As part of the complex skin barrier dysfunction, abnormalities in lipid organization and microbiome composition have been described. We set out to systematically investigate the composition of the stratum corneum lipidome, skin microbiome and skin physiology parameters at three different body sites in patients with AD and healthy volunteers. Methods: We analysed tape strips from different body areas obtained from 10 adults with AD and 10 healthy volunteers matched for FLG mutation status for 361 skin lipid species using the Metabolon mass spectrometry platform. 16S rRNA data were available from all probands. Results: Our study showed that the lipid composition differs significantly between body sites and between AD patients and healthy individuals. Ceramide species NS was significantly higher in AD patients compared to healthy volunteers and was also higher in AD patients with a FLG mutation compared to AD patients without a FLG mutation. The correlation analysis of skin lipid alterations with the microbiome showed that Staphylococcus colonization in AD is positively correlated with ceramide subspecies AS, ADS, NS and NDS. Conclusion: This is the first study to reveal site‐specific lipid alterations and correlations with the skin microbiome in AD. [ABSTRACT FROM AUTHOR]

Published
2021
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44. Predictive value of food sensitization and filaggrin mutations in children with eczema

Author

Filipiak-Pittroff, Birgit, Schnopp, Christina, Berdel, Dietrich, Naumann, Aline, Sedlmeier, Simon, Onken, Anna, Rodriguez, Elke, Fölster-Holst, Regina, Baurecht, Hansjörg, Ollert, Markus, Ring, Johannes, Cramer, Claudia, von Berg, Andrea, Bauer, Carl Peter, Herbarth, Olf, Lehmann, Irina, Schaaf, Beate, Koletzko, Sibylle, Wichmann, Heinz-Erich, Heinrich, Joachim, and Weidinger, Stephan

Published
2011
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45. Analysis of the individual and aggregate genetic contributions of previously identified serine peptidase inhibitor Kazal type 5 (SPINK5), kallikrein-related peptidase 7 (KLK7), and filaggrin (FLG) polymorphisms to eczema risk

Author

Weidinger, Stephan, Baurecht, Hansjörg, Wagenpfeil, Stefan, Henderson, John, Novak, Natalija, Sandilands, Aileen, Chen, Huijia, Rodriguez, Elke, OʼRegan, Grainne M., Watson, Rosemarie, Liao, Haihui, Zhao, Yiwei, Barker, Jonathan N.W.N., Allen, Michael, Reynolds, Nick, Meggitt, Simon, Northstone, Kate, Smith, George D., Strobl, Carolin, Stahl, Caroline, Kneib, Thomas, Klopp, Norman, Bieber, Thomas, Behrendt, Heidrun, Palmer, Colin N.A., Wichmann, H.-Erich, Ring, Johannes, Illig, Thomas, McLean, Irwin W.H., and Irvine, Alan D.

Published
2008

46. Filaggrin mutations, atopic eczema, hay fever, and asthma in children

Author

Weidinger, Stephan, OʼSullivan, Maureen, Illig, Thomas, Baurecht, Hansjörg, Depner, Martin, Rodriguez, Elke, Ruether, Andreas, Klopp, Norman, Vogelberg, Christian, Weiland, Stephan K., McLean, Irwin W.H., von Mutius, Erika, Irvine, Alan D., and Kabesch, Michael

Published
2008

48. RNA based individualized drug selection in breast cancer patients without patient-matched normal tissue

Author

Forster, Michael, primary, Mark, Adam, additional, Egberts, Friederike, additional, Rosati, Elisa, additional, Rodriguez, Elke, additional, Stanulla, Martin, additional, Bauerschlag, Dirk, additional, Schem, Christian, additional, Maass, Nicolai, additional, Amallraja, Anu, additional, Murphy, Karla K., additional, Prouse, Bruce R., additional, Sulaiman, Raed A., additional, Young, Brandon M., additional, Mathiak, Micaela, additional, Hemmrich-Stanisak, Georg, additional, Ellinghaus, David, additional, Weidinger, Stephan, additional, Rosenstiel, Philip, additional, Arnold, Norbert, additional, Leyland-Jones, Brian, additional, Williams, Casey B., additional, Franke, Andre, additional, and Meißner, Tobias, additional

Published
2018
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49. A genome-wide association study reveals 2 new susceptibility loci for atopic dermatitis

Author

Schaarschmidt, Heidi, Ellinghaus, David, Rodríguez, Elke, Kretschmer, Anja, Baurecht, Hansjörg, Lipinski, Simone, Meyer-Hoffert, Ulf, Harder, Jürgen, Lieb, Wolfgang, Novak, Natalija, Fölster-Holst, Regina, Esparza-Gordillo, Jorge, Marenholz, Ingo, Ruschendorf, Franz, Hubner, Norbert, Reischl, Eva, Waldenberger, Melanie, Gieger, Christian, Illig, Thomas, Kabesch, Michael, Zhang, Xue-Jun, Xiao, Feng-Li, Lee, Young-Ae, Franke, Andre, and Weidinger, Stephan

Published
2015
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50. Meta-analysis identifies seven susceptibility loci involved in the atopic march

Author

Marenholz, Ingo, Esparza-Gordillo, Jorge, Rüschendorf, Franz, Bauerfeind, Anja, Strachan, David P., Spycher, Ben D., Baurecht, Hansjörg, Margaritte-Jeannin, Patricia, Sääf, Annika, Kerkhof, Marjan, Ege, Markus, Baltic, Svetlana, Matheson, Melanie C., Li, Jin, Michel, Sven, Ang, Wei Q., McArdle, Wendy, Arnold, Andreas, Homuth, Georg, Demenais, Florence, Bouzigon, Emmanuelle, Söderhäll, Cilla, Pershagen, Göran, de Jongste, Johan C., Postma, Dirkje S., Braun-Fahrländer, Charlotte, Horak, Elisabeth, Ogorodova, Ludmila M., Puzyrev, Valery P., Bragina, Elena Yu, Hudson, Thomas J., Morin, Charles, Duffy, David L., Marks, Guy B., Robertson, Colin F., Montgomery, Grant W., Musk, Bill, Thompson, Philip J., Martin, Nicholas G., James, Alan, Sleiman, Patrick, Toskala, Elina, Rodriguez, Elke, Fölster-Holst, Regina, Franke, Andre, Lieb, Wolfgang, Gieger, Christian, Heinzmann, Andrea, Rietschel, Ernst, Keil, Thomas, Cichon, Sven, Nöthen, Markus M., Pennell, Craig E., Sly, Peter D., Schmidt, Carsten O., Matanovic, Anja, Schneider, Valentin, Heinig, Matthias, Hübner, Norbert, Holt, Patrick G., Lau, Susanne, Kabesch, Michael, Weidinger, Stefan, Hakonarson, Hakon, Ferreira, Manuel A. R., Laprise, Catherine, Freidin, Maxim B., Genuneit, Jon, Koppelman, Gerard H., Melén, Erik, Dizier, Marie- Hélène, Henderson, A John, Lee, Young Ae, Gastroenterology & Hepatology, Pediatrics, Erasmus MC other, and Groningen Research Institute for Asthma and COPD (GRIAC)

Subjects
HAY-FEVER, Male, Kinesins, Filaggrin Proteins, FOOD ALLERGY, FILAGGRIN MUTATIONS, immune system diseases, Child, RISK, BIRTH COHORT, Nuclear Proteins, Middle Aged, Neoplasm Proteins, DNA-Binding Proteins, Phenotype, Child, Preschool, Disease Progression, Female, ddc:500, Adult, Adolescent, Genotype, Nerve Tissue Proteins, 610 Medicine & health, Polymorphism, Single Nucleotide, Article, Dermatitis, Atopic, Ikaros Transcription Factor, Young Adult, 360 Social problems & social services, Humans, Genetic Predisposition to Disease, JUVENILE MYOCLONIC EPILEPSY, ddc:610, Receptor, Fibroblast Growth Factor, Type 1, CHROMOSOME 11Q13, Calcium-Binding Proteins, CHILDHOOD ASTHMA, Membrane Proteins, Asthma, Repressor Proteins, DERMATITIS, Adaptor Proteins, Vesicular Transport, Amino Acid Transport Systems, Neutral, Logistic Models, Cardiovascular and Metabolic Diseases, GENOMEWIDE ASSOCIATION, Interleukin-4, Carrier Proteins, Genome-Wide Association Study, Transcription Factors
Abstract

Eczema often precedes the development of asthma in a disease course called the ‘atopic march'. To unravel the genes underlying this characteristic pattern of allergic disease, we conduct a multi-stage genome-wide association study on infantile eczema followed by childhood asthma in 12 populations including 2,428 cases and 17,034 controls. Here we report two novel loci specific for the combined eczema plus asthma phenotype, which are associated with allergic disease for the first time; rs9357733 located in EFHC1 on chromosome 6p12.3 (OR 1.27; P=2.1 × 10−8) and rs993226 between TMTC2 and SLC6A15 on chromosome 12q21.3 (OR 1.58; P=5.3 × 10−9). Additional susceptibility loci identified at genome-wide significance are FLG (1q21.3), IL4/KIF3A (5q31.1), AP5B1/OVOL1 (11q13.1), C11orf30/LRRC32 (11q13.5) and IKZF3 (17q21). We show that predominantly eczema loci increase the risk for the atopic march. Our findings suggest that eczema may play an important role in the development of asthma after eczema., The development of asthma following eczema is known as the atopic march. Here the authors conduct a GWAS on affected children and identify two novel loci associated with the disease phenotype.

Published
2015
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