Researchers identify epigenetic signature associated with 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 Institute for Biomedical Research (IDIBELL) have identified an associated epigenetic signature to the development of multisystem inflammatory syndrome in children (MIS-C) after infection with the SARS-CoV-2 virus. The signature was named EPIMISC, in line with previous studies on the epigenetics of COVID-19 by the same team.
SARS-CoV-2 virus infection and development of COVID-19 disease has been a serious health, social and economic problem over the past two years. The massive introduction of vaccines has allowed some return to normality, but there are still many unanswered questions. One of the enigmas of the virus infection has been the remarkable resilience of children to present with severe COVID-19. However, a small percentage of the pediatric population affected by the virus has suffered from a serious health condition called Multisystem Inflammatory Syndrome in Children (MIS-C), also known as Pediatric Multisystem Inflammatory Syndrome (PIMS), which requires admission to an intensive care unit (ICU). ) in about 60% of cases.
In MIS-C, different parts of the body can become inflamed, including the heart, lungs, kidneys, brain, skin, eyes, or gastrointestinal organs. Factors associated with the occurrence of MIS-C beyond the presence of the virus are unknown.
In a recent article published in the journal ECMedicineClinicalthe sister magazine of The Lancet for rapid communication of clinical results, 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 Professor ICREA and Head of the Neurometabolic Diseases Group of the Bellvitge Institute for Biomedical Research (IDIBELL), and member of the Spanish network for rare diseases CIBERER, demonstrates that there are epigenetic changes linked to the triggering of MIS-C, less in the cohort population studied.
“COVID-19 disease in adults is characterized by difficulty breathing, while the studied rare syndrome associated with the same virus in children affects many more organs and can have serious consequences. As the bases of the disease are unknown, we decided to compare the epigenome of healthy children, children with COVID-19 without MIS-C and children with COVID-19 who had MIS-C. VS”, explains Dr. Esteller in relation to the article and adds: “We discovered that MIS-C is characterized by a specific dysregulation of epigenetic cellular programming that leads to a landscape of hyperinflammation that can damage tissues.”.
The results of the study, signed by Dr. Verónica Dávalos and Carlos A. García-Prieto as first authors, showed that specific genes were affected in patients, such as those associated with T-cell activation, natural killer cells, antigen recognition and coagulation. This pattern of epigenetic dysregulation has also been observed in Kawasaki syndrome, another inflammatory disease that peaked in 2009 and possibly linked to infection with the influenza A H1N1 virus.
Interestingly, two of the 33 DNA methylation events that define the EPIMISC signature are also characteristic of adults without 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 post-infectious inflammatory complications and could be treated differently from the initial phase of viral infection. . In this regard, the researchers hypothesize that pharmacological inhibition of the CUL2 gene, an inflammation mediator, could be useful for MIS-C patients because it is known to protect against hyperinflammatory responses.
This is an unusual feature and Dr. Pujol notes that “it is interesting to see that two disorders that exhibit similar clinical manifestations, MIS-C and Kawasaki, also share a common epigenetic signature, which is different from epigenetic signature caused by other viruses”. including HIV”. Along the same lines, Dr. Esteller concludes that “it appears that in both syndromes, MIS-C and Kawasaki, there is an overreaction of the children’s immune system to a viral attack. Knowing the mechanisms triggering the two diseases will give us better tools.” to diagnose and treat them.
Josep Carreras Leukemia Research Institute
Davalos, V. et al. (2022) Epigenetic profiling linked to multisystem inflammatory syndrome in children (MIS-C): a multicenter retrospective study. ECClinical Medicine. doi.org/10.1016/j.eclinm.2022.101515.