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Medicine and Research

Covid-19 Vaccines: Cause of Heart Muscle Inflammation Detected

Auto-antibodies responsible for rare side effect

Scientific name of the study

IL-1RA Antibodies in Myocarditis after SARS-CoV-2 Vaccination

In up to ten out of a total of one hundred thousand patients, myocarditis develops after mRNA vaccination against Corona. Younger male patients in particular are affected by this rare side effect. Unlike the much more common myocarditis following covid 19 infection, the disease is usually very mild after vaccination. But what exactly is the trigger? An international team of researchers led by hematologist and cancer specialist Lorenz Thurner from Saarland University Hospital has discovered a mechanism behind this in their research.

First Indications

Various meta-studies had shown that mainly male patients between 14 and 30 years of age developed myocarditis after mRNA vaccination, typically after the second vaccine dose. Researchers also found an auto-antibody in the blood when studying children and adolescents who were severely ill with PIMS, also called multisystemic inflammatory syndrome (MIS-C), or had a severe Covid19 course after a Covid19 challenge.

Eliminating a Key Antagonist

 "We know that the messenger interleukin-1 (IL-1) can trigger inflammation of the pericardium, the heart muscle, but also inflammation throughout the body. Its endogenous counterpart is the so-called interleukin-1 receptor antagonist (IL-1Ra). This prevents interleukin-1 signaling and thereby inhibits inflammation. However, the auto-antibodies disable this antagonist," explains Lorenz Thurner. The research team wondered whether the same mechanism could also be responsible for the development of the rare vaccination side effect. 

Confusion in the Cell Provides Free Play

The researchers examined blood and plasma from 40 patients who underwent biopsy-determined myocarditis following SARS-CoV-2 vaccination. They compared the data with those of 214 vaccinated healthy comparison subjects and 125 patients with myocarditis who had contracted it before the pandemic. And indeed, the 40 patients had the same auto-antibody. "We were able to find out that the interleukin-1 receptor antagonist in these patients carries an additional phosphate residue at one point in its protein chain. This change is recognized by the specific immune system as foreign, so that the body's own defense player IL-1Ra is instead "read" as a potential external troublemaker and then neutralized by the antibodies. This gives the inflammatory messenger interleukin-1 free rein, resulting in a dangerous imbalance," says Lorenz Thurner.  

Research Success Through Interdisciplinary Collaboration

Decisive for this proof was the cooperation in an interdisciplinary team. In addition to hematologist Lorenz Thurner, the team included pediatric cardiologist Jochen Pfeifer and cardiologist Michael Böhm from Saarland University Hospital in Homburg, pathologist Karin Klingel from Tübingen University Hospital, who specializes in myocarditis, pediatric pneumologist Bernhard Thurner from the Allgäu Hospital Association, immunologist Christoph Kessel from Münster University Hospital, who specializes in hyperinflammation, and researchers at the Competence Network for Congenital Heart Defects and cardiologists from Germany and Israel.

Finally a Clearer Picture

Why this change in the interleukin-1 receptor antagonist is found primarily in male patients between the ages of 14 and 30, how exactly the hyperphosphorylation of IL-1Ra occurs, and whether it actually also triggers the autoimmune response can now be further explored. "Now we have a clearer picture of the mechanisms and know what to look for, for example, also in connection with the severe sequelae in Covid-19," says Jochen Pfeifer.

mRNA Vaccination Remains Urgent Recommendation

Nevertheless, Hashim Abdul-Khaliq and Michael Böhm, together with their colleagues, continue to explicitly recommend mRNA vaccination, especially for congenital heart defects: "The rare side effect of mRNA vaccination is disproportionate to its great benefit. Vaccine-induced myocarditis is readily treatable. The same cannot be said of the much more common covid-19 myocarditis. It is far more threatening," says Hashim Abdul-Khaliq, Director of Pediatric Cardiology at Saarland University Hospital and Vice Chairman of the Board of the Competence Network for Congenital Heart Defects.

  • Wissenschaftliche Details zur Studie

    Auto-antibodies give heart muscle inflammation free rein. © iStockphoto.com | wildpixel
    Auto-antibodies give heart muscle inflammation free rein.

    Erfahren Sie mehr zum Studiendesign, den Materialien und Methoden, sowie zu den Hintergründen der Studie.

    Learn more about the study design, material and methods, as well as the background of the study:

    Publications

    • 21.9.2022

      IL-1RA Antibodies in Myocarditis after SARS-CoV-2 Vaccination.

      Thurner L, Kessel C, Fadle N, Regitz E, Seidel F, Kindermann I, Lohse S, Kos I, Tschöpe C, Kheiroddin P, Kiblboeck D, Hoffmann MC, Bette B, Carbon G, Cetin O, Preuss KD, Christofyllakis K, Bittenbring JT, Pickardt T, Fischer Y, Thiele H, Baldus S, Stangl K, Steiner S, Gietzen F, Kerber S, Deneke T, Jellinghaus S, Linke A, Ibrahim K, Grabmaier U, Massberg S, Thilo C, Greulich S, Gawaz M, Mayatepek E, Meyer-Dobkowitz L, Kindermann M, Birk E, Birk M, Lainscak M, Foell D, Lepper PM, Bals R, Krawczyk M, Mevorach D, Hasin T, Keren A, Kabesch M, Abdul-Khaliq H, Smola S, Bewarder M, Thurner B, Böhm M, Pfeifer J, Klingel K

      The New England journal of medicine, (2022). Show this publication on PubMed.


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