International Journal of Molecular Sciences (Oct 2023)

Preliminary Evidence of the Differential Expression of Human Endogenous Retroviruses in Kawasaki Disease and SARS-CoV-2-Associated Multisystem Inflammatory Syndrome in Children

  • Emanuela Balestrieri,
  • Elena Corinaldesi,
  • Marianna Fabi,
  • Chiara Cipriani,
  • Martina Giudice,
  • Allegra Conti,
  • Antonella Minutolo,
  • Vita Petrone,
  • Marialaura Fanelli,
  • Martino Tony Miele,
  • Laura Andreozzi,
  • Fiorentina Guida,
  • Emanuele Filice,
  • Matteo Meli,
  • Sandro Grelli,
  • Guido Rasi,
  • Nicola Toschi,
  • Francesco Torcetta,
  • Claudia Matteucci,
  • Marcello Lanari,
  • Paola Sinibaldi-Vallebona

DOI
https://doi.org/10.3390/ijms242015086
Journal volume & issue
Vol. 24, no. 20
p. 15086

Abstract

Read online

Multisystem inflammatory syndrome in children (MIS-C) is a postinfectious sequela of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with some clinical features overlapping with Kawasaki disease (KD). Our research group and others have highlighted that the spike protein of SARS-CoV-2 can trigger the activation of human endogenous retroviruses (HERVs), which in turn induces inflammatory and immune reactions, suggesting HERVs as contributing factors in COVID-19 immunopathology. With the aim to identify new factors involved in the processes underlying KD and MIS-C, we analysed the transcriptional levels of HERVs, HERV-related genes, and immune mediators in children during the acute and subacute phases compared with COVID-19 paediatric patients and healthy controls. The results showed higher levels of HERV-W, HERV-K, Syn-1, and ASCT-1/2 in KD, MIS-C, and COV patients, while higher levels of Syn-2 and MFSD2A were found only in MIS-C patients. Moreover, KD and MIS-C shared the dysregulation of several inflammatory and regulatory cytokines. Interestingly, in MIS-C patients, negative correlations have been found between HERV-W and IL-10 and between Syn-2 and IL-10, while positive correlations have been found between HERV-K and IL-10. In addition, HERV-W expression positively correlated with the C-reactive protein. This pilot study supports the role of HERVs in inflammatory diseases, suggesting their interplay with the immune system in this setting. The elevated expression of Syn-2 and MFSD2A seems to be a distinctive trait of MIS-C patients, allowing to distinguish them from KD ones. The understanding of pathological mechanisms can lead to the best available treatment for these two diseases, limiting complications and serious outcomes.

Keywords