Preliminary Evidence of the Differential Expression of HERVs in Kawasaki Disease and SARS-CoV-2-Associated MIS-C, 2023, Balestrieri et al.

Preliminary Evidence of the Differential Expression of Human Endogenous Retroviruses in Kawasaki Disease and SARS-CoV-2-Associated Multisystem Inflammatory Syndrome in Children
Balestrieri, Emanuela; Corinaldesi, Elena; Fabi, Marianna; Cipriani, Chiara; Giudice, Martina; Conti, Allegra; Minutolo, Antonella; Petrone, Vita; Fanelli, Marialaura; Miele, Martino Tony; Andreozzi, Laura; Guida, Fiorentina; Filice, Emanuele; Meli, Matteo; Grelli, Sandro; Rasi, Guido; Toschi, Nicola; Torcetta, Francesco; Matteucci, Claudia; Lanari, Marcello; Sinibaldi-Vallebona, Paola

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.

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