| Autor: |
Tilman R. Rohrer, Jordi Anton, Michael Boehm, Hashim Abdul-Khaliq, Igor Kos, Harald Sauer, Hendrik Juenger, Jochen Pfeifer, Michael Fedlmeier, Rosa Maria Pino-Ramirez, Sigrun Smola, Helmut Wittkowski, Bernhard Thurner, Christoph Kessel, Lorenz Thurner, Sascha Meyer, Moritz Bewarder, Marie-Christin Hoffmann, Soeren L Becker, Yvan Fischer, Stefan Lohse, Natalie Fadle, Evi Regitz, Klaus Roemer, Klaus-Dieter Preuss, Dirk Foell, Katja Masjosthusmann, Kristina Heyne, Marie-Claire Detemple |
| Rok vydání: |
2021 |
| Předmět: |
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| DOI: |
10.1101/2021.09.08.21263027 |
| Popis: |
Multisystem inflammatory syndrome in children (MIS-C or PIMS) is a rare but serious complication after an infection with SARS-CoV-2. A possible involvement of pathogenetically relevant autoantibodies has been discussed. Recently neutralizing autoantibodies against anti-inflammatory receptor antagonists progranulin (PGRN) and IL-1-receptor antagonist (IL-1-Ra) were discovered in adult patients with critical COVID-19.Plasma of an index case with severe PIMS/MIS-C was analyzed for autoantibodies against IL-1-Ra and PGRN. The study was extended by a case series of 12 additional patients. In addition to ELISA for of antibodies, IL-1-Ra plasma levels were determined and IL-1-Ra was analyzed by Western-blot and isoelectric focusing. Functional activity of the autoantibodies was examined in vitro with IL-1ß reporter assays.Antibodies against IL-1-Ra could be detected in 10 of 13 (76.9%) patients with PIMS/MIS-C, but not in controls. In contrast to critical COVID-19 in adults, no IL-1-Ra antibodies of the IgM class were detected in PIMS/MIS-C. IL-1-Ra-antibodies exclusively belonged to IgG1. No antibodies directed against PGRN were detected. Western blots and ELISA showed a concomitant reduction of free IL-1-Ra plasma levels in the presence of IL-1-Ra-antibodies. The antibodies inhibited IL-1-Ra function in IL-1ß reporter cell assays. Notably, an additional, hyperphosphorylated, transiently occurring atypical isoform of IL-1-Ra was observed in all IL-1-Ra autoantibody-positive patients.To conclude, IL-1-Ra autoantibodies were observed in high frequency in children with PIMS/MIS-C. They may represent a diagnostic and pathophysiologically relevant marker for PIMS/MIS-C. Their generation is likely to be triggered by an atypical, hyperphosphorylated isoform of IL-1-Ra. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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