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8. COVID-19 patients exhibit less pronounced immune suppression compared with bacterial septic shock patients

Author

Kox, Matthijs, Frenzel, Tim, Schouten, Jeroen, van de Veerdonk, Frank L., Koenen, Hans J. P. M., Pickkers, Peter, Hemelaar, Pleun, Beunders, Remi, van der Hoeven, Johannes, van der Velde, Sjef, van der Eng, Hetty, Rovers, Noortje, Klop-Riehl, Margreet, Gerretsen, Jelle, Kooistra, Emma, Waalders, Nicole, Claassen, Wout, Heesakkers, Hidde, van Schaik, Tirsa, Netea, Mihai, Joosten, Leo, Janssen, Nico, Grondman, Inge, de Nooijer, Aline, de Mast, Quirijn, Jaeger, Martin, Kouijzer, Ilse, Dijkstra, Helga, Lemmers, Heidi, van Crevel, Reinout, van de Maat, Josephine, Nijman, Gerine, Moorlag, Simone, Taks, Esther, Debisarun, Priya, Wertheim, Heiman, Hopman, Joost, Rahamat-Langendoen, Janette, Bleeker-Rovers, Chantal, Fasse, Esther, van Rijssen, Esther, Kolkman, Manon, van Cranenbroek, Bram, Smeets, Ruben, Joosten, Irma, and VU University medical center

Subjects
Secondary infection, lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], Inflammation, Other Research Radboud Institute for Molecular Life Sciences [Radboudumc 0], Critical Care and Intensive Care Medicine, Monocytes, 03 medical and health sciences, 0302 clinical medicine, Immune system, Immune suppression, Research Letter, Medicine, Prospective cohort study, COVID, mHLA-DR, Innate immune system, business.industry, Septic shock, SARS-CoV-2, HLA-DR, Other Research Radboud Institute for Health Sciences [Radboudumc 0], lcsh:Medical emergencies. Critical care. Intensive care. First aid, COVID-19, 030208 emergency & critical care medicine, Metabolic Disorders Radboud Institute for Molecular Life Sciences [Radboudumc 6], lcsh:RC86-88.9, medicine.disease, Pneumonia, lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], Shock (circulatory), Immunology, medicine.symptom, business, Inflammatory diseases Radboud Institute for Molecular Life Sciences [Radboudumc 5]
Abstract

At the end of March 2020, there were in excess of 800.000 confirmed cases of coronavirus disease 2019 (COVID-19) worldwide. Several reports suggest that, in severe cases, COVID-19 may cause a hyperinflammatory 9cytokine storm9. However, unlike SARS-CoV infection, high levels of anti-inflammatory mediators have also been reported in COVID-19 patients. One study reported that 16% of COVID-19 patients who died developed secondary infection, which might indicate an immune-suppressed state. We explored kinetics of mHLA-DR expression, the most widely used marker of innate immune suppression in critically ill patients, in COVID- 19 patients admitted to the ICU. Twenty-four confirmed COVID-19 patients were included, of which 75% was male and 79% had comorbidities. All patients were mechanically ventilated and exhibited large high levels of inflammatory parameters such as CRP and PCT. Although mHLA-DR expression levels in COVID-19 patients were lower than those observed in healthy subjects, the extent of suppression was less pronounced than observed in bacterial septic shock patients. mHLA-DR expression kinetics revealed no change over time. None of the COVID-19 patients developed a secondary infection. In conclusion, despite a pronounced inflammatory response, mHLA-DR expression kinetics indicate more moderate innate immune suppression in COVID-19 patients compared with bacterial septic shock patients. These data signify that innate immune suppression as a negative feedback mechanism following PAMP-induced inflammation appears less pronounced in COVID-19.

Published
2020
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9. Increased HLA-G Expression in Term Placenta of Women with a History of Recurrent Miscarriage Despite Their Genetic Predisposition to Decreased HLA-G Levels

Author

Craenmehr, Moniek, primary, Nederlof, Iris, additional, Cao, Milo, additional, Drabbels, Jos, additional, Spruyt-Gerritse, Marijke, additional, Anholts, Jacqueline, additional, Kapsenberg, Hanneke, additional, Stegehuis, Janine, additional, van der Keur, Carin, additional, Fasse, Esther, additional, Haasnoot, Geert, additional, van der Hoorn, Marie-Louise, additional, Claas, Frans, additional, Heidt, Sebastiaan, additional, and Eikmans, Michael, additional

Published
2019
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11. Increased dermal expression of chromatin-associated protein HMGB1 and concomitant T-cell expression of the DNA RAGE in patients with psoriasis vulgaris

Author

Strohbuecker,Lisa, Koenen,Hans, van Rijssen,Esther, van Cranenbroek,Bram, Fasse,Esther, Joosten,Irma, Körber,Andreas, Bergmann,Christoph, Strohbuecker,Lisa, Koenen,Hans, van Rijssen,Esther, van Cranenbroek,Bram, Fasse,Esther, Joosten,Irma, Körber,Andreas, and Bergmann,Christoph

Abstract

Lisa Strohbuecker,1 Hans Koenen,2 Esther van Rijssen,2 Bram van Cranenbroek,2 Esther Fasse,2 Irma Joosten,2 Andreas Körber,1 Christoph Bergmann3 1Department of Dermatology, University Hospital Essen, 45147 Essen, Germany; 2Department of Laboratory Medicine, Laboratory of Medical Immunology, Radboud University Medical Center, Nijmegen, the Netherlands; 3Department of Otorhinolaryngology, University Hospital Essen, 45147 Essen, Germany Purpose: Psoriasis vulgaris (PV) is an autoimmune-related chronic inflammatory disease of the skin, with both vascular and metabolic effects. Aggravating factors have been identified that initiate and maintain inflammation, including expression of Th1-, Th17-, and Th22-cell derived cytokines. Recently, we showed that the evolutionarily ancient and highly conserved damage-associated molecular pattern molecule “high mobility group box 1 (HMGB1)” is significantly increased in the serum of PV patients with disease progression and is decreased under standard therapies. Materials and methods: To better understand the role of HMGB1 in the pathogenesis of PV, we recruited 22 untreated psoriatic patients with either mild or severe disease, defined by the Psoriasis Area Severity Index. We assessed HMGB1 and receptor for advanced glycation end products (RAGE) expression in the skin by immunohistochemistry and analyzed the immune-phenotype of Treg and Th17 cells by flow cytometry. Results: We found increased staining for HMGB1 in the dermis of psoriatic plaques in comparison to uninvolved skin of patients with PV. In addition, the major histocompatibility complex class III-encoded DNA and HMGB1 RAGE, induced by HMGB1, were highly expressed on psoriatic CD8+ T cells and CD4+ Treg. High expression of HMGB1 in the lesional skin was associated with even higher expression of its receptor, RAGE, on the cell surface of keratinocytes in patients with severe PV. Conclusion: The presence of HMGB1 and RAGE signaling may impact orc

Published
2019

12. Lymphoid Aggregates of Tolerogenic B Cells Feature in the Dynamic Immunological Landscape of the Uterus from Pre-Pregnancy to Delivery

Author

Benner, Marilen, primary, Feyaerts, Dorien, additional, García, Celia Cartagena, additional, İnci, Nurcan, additional, López, Sergi Cedó, additional, Fasse, Esther, additional, Shadmanfar, Wijs, additional, van der Heijden, Olivier W.H., additional, Ferwerda, Gerben, additional, Joosten, Irma, additional, and van der Molen, Renate G., additional

Published
2019
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13. Humanized Mouse Model of Skin Inflammation Is Characterized by Disturbed Keratinocyte Differentiation and Influx of IL-17A Producing T Cells

Author

de Oliveira, Vivian L., primary, Keijsers, Romy R. M. C., additional, van de Kerkhof, Peter C. M., additional, Seyger, Marieke M. B., additional, Fasse, Esther, additional, Svensson, Lars, additional, Latta, Markus, additional, Norsgaard, Hanne, additional, Labuda, Tord, additional, Hupkens, Pieter, additional, van Erp, Piet E. J., additional, Joosten, Irma, additional, and Koenen, Hans J. P. M., additional

Published
2012
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19. Increased dermal expression of chromatin-associated protein HMGB1 and concomitant T-cell expression of the DNA RAGE in patients with psoriasis vulgaris.

Author

Strohbuecker L, Koenen H, van Rijssen E, van Cranenbroek B, Fasse E, Joosten I, Körber A, and Bergmann C

Abstract

Purpose: Psoriasis vulgaris (PV) is an autoimmune-related chronic inflammatory disease of the skin, with both vascular and metabolic effects. Aggravating factors have been identified that initiate and maintain inflammation, including expression of Th1-, Th17-, and Th22-cell derived cytokines. Recently, we showed that the evolutionarily ancient and highly conserved damage-associated molecular pattern molecule "high mobility group box 1 (HMGB1)" is significantly increased in the serum of PV patients with disease progression and is decreased under standard therapies., Materials and Methods: To better understand the role of HMGB1 in the pathogenesis of PV, we recruited 22 untreated psoriatic patients with either mild or severe disease, defined by the Psoriasis Area Severity Index. We assessed HMGB1 and receptor for advanced glycation end products (RAGE) expression in the skin by immunohistochemistry and analyzed the immune-phenotype of Treg and Th17 cells by flow cytometry., Results: We found increased staining for HMGB1 in the dermis of psoriatic plaques in comparison to uninvolved skin of patients with PV. In addition, the major histocompatibility complex class III-encoded DNA and HMGB1 RAGE, induced by HMGB1, were highly expressed on psoriatic CD8+ T cells and CD4+ Treg. High expression of HMGB1 in the lesional skin was associated with even higher expression of its receptor, RAGE, on the cell surface of keratino-cytes in patients with severe PV., Conclusion: The presence of HMGB1 and RAGE signaling may impact orchestration of chronic inflammation in PV which might have implications for Treg and Th17 cells., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Published
2019
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