Antihuman Endogenous Retrovirus Immune Response and Adaptive Dysfunction in Autism

Carta, Alessandra; Manca, Maria Antonietta; Scoppola, Chiara; Simula, Elena Rita; Noli, Marta; Ruberto, Stefano; Conti, Marta Helena Souza De; Zarbo, Ignazio Roberto; Antonucci, Roberto; Sechi, Leonardo Antonio; Sotgiu, Stefano

doi:10.3390/biomedicines10061365

Cited by 3 publications

(2 citation statements)

References 28 publications

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“…Results showed that the risk for ASD was increased in children inheriting from fathers the AA genotype of the rs4581 GC gene (vitamin D binding protein). Recently, an association between serum human endogenous retrovirus (HERV)-W-specific antibodies (Abs) and global adaptive functioning in ASD children was described [ 59 ]. These results, besides suggesting a possible use of such Abs to monitor clinical severity in ASD, reinforce the suggestion that immune activation and chronic neuro-inflammation are present in ASD [ 60 , 61 , 62 ].…”

Section: Discussionmentioning

confidence: 99%

GC1f Vitamin D Binding Protein Isoform as a Marker of Severity in Autism Spectrum Disorders

et al. 2022

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Autism spectrum disorders (ASD) are characterized by a wide spectrum of clinical, behavioral, and cognitive manifestations. It is, therefore, crucial to investigate possible biomarkers associated with specific ASD phenotypes. Ample literature suggests a possible role for vitamin D (VD) in influencing ASD clinical phenotypes. We analyzed three vitamin D binding protein gene (DBP) functional polymorphisms (rs2282679, rs7041, and rs4588), which are involved in the modulation of vitamin D serum concentration in 309 ASD children and 831 healthy controls. Frequency comparisons of single nucleotide polymorphisms (SNPs) alleles, genotypes, and GC isoforms (GC1f, G1s, and GC2)—generated by the combination of rs7041 and rs4588 alleles—were correlated with ASD diagnostic, behavioral, and functioning scales. The GC1f isoform was significantly more frequent in ASD compared with controls (18.6% vs. 14.5% pc = 0.02). Significantly higher scores for item 15 of the Childhood Autism Rating Scale (CARS) and lower ones for the Children’s Global Assessment Scale (CGAS) functioning scales were seen in ASD carrying the GC1f isoform. In GC phenotype analysis, a gradient of severity for overall CARS scores and CARS item 15 was observed, with scores decreasing according to the presence of GC1f-GC1f > GC1f-GC1s > GC1s-GC1s > GC1f-GC2 > GC2-GC2 isoforms. Similarly, lower CGAS scores were seen in carriers of the GC1f-GC1f isoform, whereas higher scores were present in those carrying GC2-GC2 (p = 0.028). This is the first study to evaluate possible relationships between GC variants and the different aspects of ASD in Italian ASD children. Results, although needing to be validated in ampler cohorts, suggest that the GC1f isoform could be a marker of severity in ASD that may be useful in establishing the intensity of therapeutic and rehabilitative protocols.

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Section: Discussionmentioning

confidence: 99%

GC1f Vitamin D Binding Protein Isoform as a Marker of Severity in Autism Spectrum Disorders

et al. 2022

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“…In ASD patients, the abnormality of ERVs activity is manifested as an elevation of HERV-H expression [194,195] and a reduction in HERV-W expression in PBMCs [195]. Moreover, a high expression of HERV-H has been linked to severe speech and motor deficits [195], whereas an anti-HERV-W immune response negatively correlates with social and adaptive competence in individuals with ASD [196]. These findings have been preliminarily validated in two commonly used ASD mouse models, BTBR T+tf/J inbred mice and CD-1 outbred mice with in-utero treatment of valproic acid (VPA).…”

Section: Neurodevelopmental Disordersmentioning

confidence: 99%

Decoding Neurological Mysteries: The Potential Impact of Endogenous Retroviruses on Brain Health

Li,

Liao,

Liu

et al. 2024

Stress and Brain

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Endogenous retroviruses (ERVs), remnants of ancient viral invasions, make up a significant part of the mammalian genomes. ERVs are typically held in check by complex epigenetic mechanisms, which serve to limit their expansion and potential adverse effects on the genome. However, ERVs can become aberrantly activated in response to stressful challenges, contributing to progression in pathological conditions, including cancer, inflammation, auto-immune disorders, and aging, through various mechanisms. Notably, ERV activation is also detected in the brain and is increasingly recognized as an important factor in neuropsychiatric disorders. In this review, we encapsulate the general understanding of ERVs in both physiological and pathological states and compiled evidence for ERV activation across a spectrum of neuropsychiatric disorders, along with current studies exploring the underlying mechanisms. Despite the accumulating body of evidence, research in this field remains in its infancy and faces substantial challenges. Further studies are warranted to enhance our understanding of ERV activation mechanisms and their roles in neuropsychological conditions, potentially contributing to the development of innovative therapeutic interventions.

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The Humoral Immune Response against Human Endogenous Retroviruses in Celiac Disease: A Case–Control Study

Bo,

Manetti,

Biggio

et al. 2024

Biomedicines

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Background: Celiac disease (CD) is an immune-mediated disease characterized by disruptions of the small intestine. Factors such as viral and bacterial infections can trigger CD. Recently, the reactivation of Human Endogenous Retroviruses (HERVs) has also been implicated, but little is known about their specific role in patients with celiac disease. Methods: The purpose of this study is to explore the humoral immune response mounted against epitopes derived from the envelope portion of three families of HERVs (HERV-K, HERV-H, and HERV-W) in CD patients. Reactivity against the HERV-K, HERV-H, and HERV-W env-su peptides was tested by indirect ELISAs in plasma of 40 patients with celiac disease and 41 age-matched healthy subjects (HCs). Results: HERV-K, HERV-H, and HERV-W env-su peptides triggered different antibody responses in CD patients compared to HCs, with a stronger reactivity (p = 0.0001). Conclusions: Present results show, for the first time, that epitopes of HERV-K, HERV-H, and HERV-W are more recognized in patients with CD. Taking into consideration their proinflammatory and autoimmune features, this might suggest that HERVs may contribute to the development of CD or its exacerbation in genetically predisposed subjects. Finally, to elucidate the interplay between gut inflammation and HERVs during the inflammatory process, further studies are required. Those investigations should focus on the expression levels of HERVs and their relationship with the immune response, specifically examining anti-transglutaminase 2 (TG2) antibody levels under both gluten-free and gluten-containing dietary conditions.

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Antihuman Endogenous Retrovirus Immune Response and Adaptive Dysfunction in Autism

Cited by 3 publications

References 28 publications

GC1f Vitamin D Binding Protein Isoform as a Marker of Severity in Autism Spectrum Disorders

GC1f Vitamin D Binding Protein Isoform as a Marker of Severity in Autism Spectrum Disorders

Decoding Neurological Mysteries: The Potential Impact of Endogenous Retroviruses on Brain Health

The Humoral Immune Response against Human Endogenous Retroviruses in Celiac Disease: A Case–Control Study

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