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If antibodies cause diseases – new approach to treat chronic inflammation

Andreas Radbruch and his team have discovered why inflammations caused by antibodies become chronic in many patients and do not respond to conventional therapies.
Antibodies protect us against infections, but they can also cause severe, chronic diseases that are difficult to treat. These antibodies are continuously secreted into the blood by so-called “plasma cells”. The DRFZ-researchers have found out that these plasma cells are located in the bone marrow. They are kept alive for a lifetime by special connective tissue cells – which explains why the diseases are chronic. Contact with the connective tissue cells triggers a specific signaling pathway in the plasma cells: The PI3K/Foxo signaling pathway makes them resistant to stress and lack of nutrients, as well as refractory to conventional treatment of chronic inflammation. However, if one interrupts this signaling pathway, the plasma cells die. These results offer new approaches to treat chronic inflammation caused by antibodies, including many rheumatic diseases, by specifically killing the antibody producing plasma cells.
These results were published in the renowned scientific journal “Cell Reports”.

Cornelis R, Hahne S, Taddeo A, Petkau G, Malko D, Durek P, Thiem M, Heiberger L, Peter L, Mohr E, Klaeden C, Tokoyoda K, Siracusa F, Hoyer BF, Hiepe F, Mashreghi MF, Melchers F, Chang HD, Radbruch A. Stromal Cell-Contact Dependent PI3K and APRIL Induced NF-κB Signaling Prevent Mitochondrial- and ER Stress Induced Death of Memory Plasma Cells. Cell Rep. 2020 Aug 4;32(5):107982. doi: 10.1016/j.celrep.2020.107982.
The project was funded by the German Research Foundation DFG and the European Research Council ERC.
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