It is my great pleasure to invite you on behalf of dr Tomasz Wypych for the next Nencki Institute Seminar which will take place on Thursday June 22^nd at 3pm in the CN lecture Hall. We will host Dr. Jeroen den Dunnen, head of the Center for Experimental and Molecular Medicine (CEMM) at the Amsterdam UMC. Jeroen’s work has been focused on both chronic inflammatory disorders such as Crohn’s Disease (Nature Communications 2018) and Multiple Sclerosis (Journal of Immunology 2020) and viral infections such as HIV. His most discovery that that antibody-dependent inflammation plays a key role in the pathogenesis of severe COVID-19 (Science Translational Medicine 2021, and Science 2021), shifted his research interests towards the goal of a better understanding of the “dark side of antibodies”. Dr. den Dunnen will give a lecture entitled: Antibodies acting as bad guys.

Abstract

Antibodies are essential to protect us from infection, since they induce various immune effector functions such as phagocytosis, ADCC, and cytokine production. However, when these effector functions are activated excessively or undesirably, they can lead to severe pathology. In this presentation, I will highlight three examples of “antibodies going bad”. First, I will discuss the role of (auto)antibodies in Multiple Sclerosis, which we show break the tolerogenic phenotype of microglia, and thereby promote inflammation in the central nervous system. Second, I will explain how IgG antibodies against the spike protein of SARS-CoV-2 drive hyper-inflammation, vascular leakage (edema), and coagulation problems (micro-thrombi) in patients suffering from severe COVID-19. These findings do not only provide an explanation for why patients only get severely ill in the second week after infection (when the viral load is already dropping), but have also yielded candidate drugs that are now tested in Phase 3 clinical trials. Finally, I will focus on how (auto)antibodies could be involved in Long-COVID/PASC, the disease characterized by long-lasting symptoms after a (mild) SARS-CoV-2 infection. These findings suggest that Long-COVID symptoms can be transferred from human to mouse.

The seminar will be followed by a get together.

With best wishes
Aleksandra Pękowska