Researchers identify an epigenetic signature linked to the development of MIS-C after COVID-19

Researchers from the Cancer Epigenetics group led by Dr. Manel Esteller of the Josep Carreras Leukemia Research Institute and Dr. Aurora Pujol, of the Bellvitge Biomedical Research Institute (IDIBELL), have identified an epigenetic signature associated with the development of Multisystem Inflammatory Syndrome in Children (MIS-C) following SARS-CoV-2 virus infection. The signature has been named EPIMISC, in line with previous studies on the epigenetics of COVID-19 by the same team.

The SARS-CoV-2 virus infection and the development of the disease COVID-19 have been a serious health, social and economic problem for the past two years. The mass implementation of vaccines has allowed for some return to normalcy, but many unanswered questions remain. One of the puzzles of infection with the virus has been the remarkable resilience of children to show severe COVID-19. However, a small percentage of the pediatric population affected by the virus had a serious health condition called Multisystem Inflammatory Syndrome in Children (MIS-C), also known as pediatric multisystem inflammatory syndrome (PIMS), requiring admission to the intensive care unit (ICU). is required. ) in about 60% of the cases.

In MIS-C, various parts of the body can become inflamed, including the heart, lungs, kidneys, brain, skin, eyes, or gastrointestinal tract. The factors associated with the appearance of MIS-C outside the presence of the virus are unknown.

In a recently published article in the magazine ECKlinicalMedicinethe sister magazine of the lancet for rapid communication of clinical findings, Dr. Manel Esteller, Director of the Josep Carreras Leukemia Research Institute (IJC), ICREA Research Professor and Professor of Genetics at the University of Barcelona and Dr. Aurora Pujol, also an ICREA Professor and Head of the Neurometabolic Diseases Group at the Bellvitge Biomedical Research Institute (IDIBELL), and a member of the Spanish Rare Disease Network CIBERER, shows that there are epigenetic changes associated with triggering MIS -C, at least in the cohort population studied.

The disease COVID-19 in adults is characterized by breathing difficulties, while the studied rare syndrome associated with the same virus in children affects many more organs and can have serious consequences. Because the basis for the condition is unknown, we decided to compare the epigenome of healthy children, children with COVID-19 without MIS-C, and children with COVID-19 who experienced MIS-C,” explains Dr. Esteller in regards to the article, adding: “We found that MIS-C is characterized by a specific deregulation of epigenetic cellular programming leading to a landscape of hyperinflammation that can damage tissues”

The results of the study, signed by Dr. Verónica Dávalos and Carlos A. García-Prieto were the first authors to show that specific genes were affected in patients, such as those associated with T lymphocyte activation, natural killer cells, antigen recognition and coagulation. This pattern of epigenetic deregulation was also observed in Kawasaki syndrome, another inflammatory disease that peaked in 2009 and may have been linked to infection with the influenza virus A H1N1.

Interestingly, two of the 33 DNA methylation events that define the EPIMISC signature are also characteristic of adults with no comorbidities who develop severe COVID-19 disease, as previously defined in the EPICOVID signature found by the same team last year. This fact confirms that both processes, MIS-C in children and severe acute respiratory distress syndrome in adults, are inflammatory post-infectious complications and can be treated differently from the initial stage of the viral infection. In this regard, researchers hypothesize that pharmacological inhibition of the CUL2 gene, a mediator of inflammation, could be useful for MIS-C patients, as it is known to protect against hyperinflammatory responses.

This is an unusual feature and Dr. Pujol notes, “It is interesting to see that two conditions that exhibit similar clinical manifestations, MIS-C and Kawasaki, also share a common epigenetic signature, which is different from the epigenetic signature caused by other viruses including HIV.” Along the same lines, Dr. Esteller concludes that “it seems that in both syndromes, MIS-C and Kawasaki, there is an exaggerated response of the immune system of children to a viral attack. If we know the mechanisms that cause both diseases, we will better have tools to diagnose and treat them”.

Source:

Reference magazine:

Davalos, V., et al. (2022) Epigenetic profiling linked to childhood multisystem inflammatory syndrome (MIS-C): a multicenter, retrospective study. ECKlinical Medicine. doi.org/10.1016/j.eclinm.2022.101515

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