International team discovers potential mechanism in the development of myocarditis after SARS-CoV-2 vaccination


Neuer potenzieller Mechanismus bei der Entstehung einer Myokarditis nach SARS-CoV-2-Impfung entdeckt

Autoantibodies against IL-1RA in myocarditis after SARS-CoV-2 vaccination. Blood plasma samples were collected from 69 patients with suspected myocarditis after receiving the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine. Endomyocardial biopsy (EMB) was performed in 61 patients and myocarditis was confirmed by EMB in 40 patients (panel A). Plasma samples obtained from 8 patients without confirmatory testing for EMB, from 21 patients in whom a diagnosis of myocarditis was ruled out, and from 40 patients in whom myocarditis was confirmed by EMB were tested for antibodies to endogenous interleukin-1 -Receptor antagonists examined (IL-1RA) and progranulin by Enzyme-Linked Immunosorbent Assay (ELISA). The data are presented sorted by the age of the study participants (panel B). OD490 denotes the optical density measured at a wavelength of 490 nm. The frequency of anti-IL-1RA antibodies in plasma samples from patients with vaccine-associated myocarditis was confirmed or excluded on EMB and sorted by age. Control participants were 214 healthy adults sampled 1 week after receiving the second dose of SARS-CoV-2 vaccine and 127 patients with myocarditis sampled before 2020 (Image C). Recognition: New England Journal of Medicine (2022). DOI: 10.1056/NEJMc2205667

A multidisciplinary, international team formed around Drs. Lorenz Thurner and Jochen Pfeifer (both University Hospital Homburg/Saar, Germany) and Dr. Christoph Kessel (University Children’s Hospital Münster, Germany) and Prof. Karin Klingel (University Hospital Tübingen, Germany). ) provides new observations related to myocarditis after SARS-CoV-2 vaccination and indicates a potential role of autoantibodies against IL-1Ra in pathophysiology.

Myocarditis as a very rare side effect of the mRNA vaccination against SARS-CoV-2, especially in male adolescents and young men, was recently described in an Israeli study. It usually occurs in a close temporal relationship after mRNA vaccination and often shows a milder course compared to classic viral and non-infectious myocarditis.

In the current study, blood samples were analyzed from male and female patients (aged 14 to 79 years), most of whom also had a myocardial biopsy. Autoantibodies to an important endogenous anti-inflammatory agent called the interleukin-1 receptor antagonist have been identified, particularly in adolescent males and young men with histologically confirmed myocarditis.

Interleukin-1 (IL-1) is an important signaling molecule involved in alerting and mobilizing the immune system during infection. However, with prolonged or high levels of IL-1 release, inflammatory responses can spiral out of control.

“We already know about the central importance of IL-1, particularly in the case of inflammation of the pericardium, heart muscle and blood vessels. However, our immune system can normally cool down inflammatory reactions itself; highly potent signaling molecules such as IL-1 in particular have natural counterparts that can slow down excessive inflammatory reactions, if necessary,” explains immunologist Christoph Kessel, Ph.D., who heads the Translational Inflammation Research Center at the Clinic for Pediatric Rheumatology and Immunology at the University Hospital Münster (UKM) ).

The interleukin-1 receptor antagonist (IL-1-Ra) is such a natural antagonist that can block the docking site for IL-1 on the cell surface and thus shut down the signaling pathway.

“However, in patients with myocarditis, we found an atypical form of IL-1-Ra that carries a specific chemical modification in the form of additional phosphorylation. The immune system then interprets this as an unknown, potentially harmful structure and starts producing antibodies against it, which can then break down and neutralize IL-1Ra as an important anti-inflammatory, paving the way for unrestricted IL-1 signaling,” says Dr. Lorenz Thurner , head of a research group at the José Carreras Center of the Clinic for Internal Medicine I of the Saarland University Hospital (UKS) in Homburg, which deals with misguided immune reactions in cancer or autoimmune diseases.

“Initial observations in the very rare cases of myocarditis following SARS-CoV-2 vaccination were incidental and linked to our previous studies identifying such autoantibodies in both MIS-C and severe and critical COVID-19 cases ‘ Thurner continues.

“In any case, it must be emphasized in this context that vaccination against SARS-CoV-2 is safe and has prevented countless serious illnesses and saved millions of lives against serious SARS-CoV-2 infections and serious complications far outweighs the risk of a mild myocarditis, which can be caused by the very rare IL-1Ra autoantibodies we have described,” says Karin Klingel, MD, Head of Cardiopathology and Pathology of Infectious Diseases at the University Hospital of Tübingen.

“Overall, this research project could only be realized through a very interdisciplinary team effort, which made participation in the project so exciting and successful,” says Jochen Pfeifer, MD, from the Department of Pediatric Cardiology at the University Hospital of Saarland (UKS).

Many other cardiologists and pediatric cardiologists, internists and paediatricians from Germany, Israel and Austria, as well as other scientists (including from the UKS Virology Department) were involved in the work.

Overall, the present study is of particular importance as it contributes to a better understanding of the mechanisms possibly underlying a very rare side effect of a SARS-CoV-2 mRNA vaccination. Despite this significant gain in knowledge, there are still many unanswered questions that the team is currently working on answering.

The research was published in New England Journal of Medicine.


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More information:
Lorenz Thurner et al, IL-1RA antibodies in myocarditis after SARS-CoV-2 vaccination, New England Journal of Medicine (2022). DOI: 10.1056/NEJMc2205667

Provided by Saarland University

Citation: International team discovers potential mechanism in the development of myocarditis after SARS-CoV-2 vaccination (2022 September 23) retrieved September 23, 2022 from https://medicalxpress.com/news/2022-09-international- team-potential-mechanism-myocarditis.html

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