Medical doctor, PhD Pediatric Emergency Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Italy Bologna, Emilia-Romagna, Italy
Background: KD and MIS-C are both characterized by an aberrant systemic inflammation whose origin is only partially understood but involving a combination of genetic, environmental, and immunologic factors. Recently, our group and others have demonstrated an aberrant expression of human endogenous retroviruses (HERVs) in blood of children with KD and MIS-C. HERVs are genetic elements originating from ancestral infection within the germ line cells by exogenous retroviruses. Although HERVs are generally silenced, peculiar HERV copies can be activated by different environmental stimuli (cytokines, exogenous viruses, hormones etc), leading to the expression of products of HERVs that have immunopathogenic properties. In vitro the spike protein of SARS-CoV-2 can trigger the activation of HERVs, which in turn can induce inflammatory and immune reactions, suggesting HERVs as contributing factors in COVID-19 immunopathology. Moreover, mRNA levels of two different families of HERVs (i.e. HERV-W and HERV-K), inflammatory and regulatory cytokines, were found to be higher in KD, MIS-C and COVID-19 compared to healthy children, also showing a phase- and disease-dependent trend. Moreover, several correlations between HERVs, regulatory cytokine IL-10 and CRP, suggestthe involvement of HERVs in the inflammation processes in KD and MISC.
Aim: To investigate antibody response against HERV-W and HERV-K epitopes and interferon regulatory factor 5 (IRF5), in serum samples from KD, MIS-C and COVID-19 children.
Methods: Prospective study including 8 KD, 16 MIS-C and 7 COVID-19 (COV) patients and 41 age- and sex-matched healthy controls (HC). Thereactivity against epitopes of HERV-H, HERV-K, HERV-W and IRF5 was tested by indirect ELISA in serum samples from patients and controls. The study was approved by Institutional Review Board.
Results: Antibodies against HERV-K are higher in both KD and MIS-C patients compared with HC, while antibodies against IRF5 were higher only in MIS-C patients compared with COV and HC.
Conclusions: Our preliminary results suggest potential immune system involvement related to humoral responses targeting specific epitopes of HERVs protein in KD. Larger cohorts of patients will be needed to confirm our preliminary data and to investigate the interplay of HERVs with interferon response in the immunopathogenesis of KD.
