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Front. Immunol. | doi: 10.3389/fimmu.2019.02013

Children with Autism Spectrum Disorder and their mothers share abnormal expression of selected endogenous retroviruses families and cytokines

 Emanuela Balestrieri1*, Chiara Cipriani1,  Claudia Matteucci1, Arianna Benvenuto2, Antonella Coniglio2, Ayele Argaw-Denboba3, Ilaria Bucci1,  Martino Tony Miele1, Sandro Grelli1,  Paolo Curatolo2 and Paola Sinibaldi-Vallebona1
  • 1Department of Experimental Medicine and Surgery, University of Rome Tor Vergata, Italy
  • 2Department of Systems Medicine, Faculty of Medicine and Surgery, University of Rome Tor Vergata, Italy
  • 3European Molecular Biology Laboratory, Italy

The Autism Spectrum Disorder (ASD) is a heterogeneous group of neurodevelopmental disorders, clinically diagnosed since the lack of reliable biomarkers. Autism aetiology is probably attributable to the combination of genetic vulnerability and environmental factors, and recently, maternal immune activation has been linked to derailed neurodevelopment, resulting in ASD in the offspring.
Human endogenous retroviruses (HERVs) are relics of ancestral infections, integrated in the human DNA. Given the HERV persistence in the genome, some of HERVs have been coopted for physiological functions during evolution, while their reactivation has been associated with several diseases, including cancer, autoimmune and neurological/psychiatric disorders. Particularly, due to their intrinsic responsiveness to external stimuli, HERVs can modulate the host immune response and in turn HERVs can be activated by the immune effectors. In previous works we demonstrated high expression of HERV-H in blood of autistic patients, closely related with the severity of the disease. Moreover, in a preclinical ASD model we proved changes of expression of several ERV families and cytokines from the intrauterine life to the adulthood and across generations via maternal lineage.
Here we analyzed the expression of HEMO and of selected HERVs and cytokines in blood from ASD patients and their parents and corresponding healthy controls, to look for a common molecular trait within family members. ASD patients and their mothers share altered expression of HERV-H and HEMO and of cytokines such as TNF-α, IFN-γ, IL-10. The multivariate regression models showed a mother-child association by HEMO activity and demonstrated in children and mothers an association between HERV-H and HEMO expression and, only in mothers, between HEMO and TNF-α expression. Furthermore, high diagnostic performance for HERV-H and HEMO was found, suggesting their potential application for the identification of ASD children and their mothers. The present data support the involvement of HERVs in ASD and suggest HERVs and cytokines as ASD-associated traits. Since ASD is a heterogeneous group of neurodevelopmental disorders, a single determinant alone could be not enough to account for the complexity, and HERV/cytokines expression could be considered in a set of biomarkers, easily detectable in blood and potentially useful for an early diagnosis.

Keywords: Autism Spectrum Disorder, HERVs, Cytokines, biomarker, mother-child association, Gene Expression, HEMO

Received: 30 Apr 2019; Accepted: 08 Aug 2019.

Copyright: © 2019 Balestrieri, Cipriani, Matteucci, Benvenuto, Coniglio, Argaw-Denboba, Bucci, Miele, Grelli, Curatolo and Sinibaldi-Vallebona. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Emanuela Balestrieri, Department of Experimental Medicine and Surgery, University of Rome Tor Vergata, Rome, Lazio, Italy, balestrieri@med.uniroma2.it