Cited by 51Autism Spectrum Disorder ResearchReproductive System and PregnancyGenetics and Neurodevelopmental Disorders

An HLA-G∗14bp insertion/deletion polymorphism associates with the development of autistic spectrum disorders

Guerini, Franca R., Bolognesi, Elisabetta, Chiappedi, Matteo, Ghezzo, Alessandro, Canevini, Maria Paola, Mensi, Martina M., Vignoli, Aglaia, Agliardi, Cristina +2 more·2015·Brain, Behavior, and Immunity

Abstract

HLA-G expressed by the trophoblast ligates KIR molecules expressed by maternal NK cells at the uterine fetal/maternal interface: this interaction is involved in generating immune tolerance during pregnancy. A 14-bp insertion in the HLA-G 3'-UTR associates with significantly reduced levels of both HLA-G mRNA and soluble HLA-G, thus hampering the efficacy of HLA-G-mediated immune tolerance during pregnancy. Because prenatal immune activation is suggested to play an important role in the onset of autistic spectrum disorders (ASD) we performed an in-depth evaluation of HLA-G polymorphisms in a well-characterized cohort of Italian families of ASD children. Results showed that frequency of both homozygous 14bp+/14bp+ genotype and 14bp+ allele was significantly higher in ASD children and their mothers compared to controls (p<0.05 in all cases); analysis of the frequency of transmission of the 14bp+ allele from parents to ASD children and their non-ASD siblings showed that the 14bp+ allele was more frequently transmitted (T) to ASD children, whereas it was preferentially not transmitted (NT) to the non-ASD siblings (overall discrepancy: p=0.02; OR: 2.6, 95% CI: 1.1-6.4). Results herein suggest that HLA-G polymorphisms are associated with ASD development, possibly as a consequence of prenatal immune activation. These data infer that the immune alterations seen in ASD are associated with the maternal-fetal interaction alone, and reinforce the observation that different genetic backgrounds characterize ASD children and their non-ASD siblings.

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Crossref · 10.1016/j.bbi.2014.10.002

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  • A 14-basepair insertion in HLA-G was found more often in individuals with ASD and in their mothers.

    “Interestingly, Guerini et al (2015) discovered a 14-basepair insertion in HLA-G that was found more often in individuals with ASD and their mothers.”

    From The Role of the Immune System in Autism Spectrum Disorder (2017) · cites this paper as Guerini et al (2015)

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Authors
Guerini, F. R., Bolognesi, E., Chiappedi, M., Ghezzo, A., Canevini, M. P., Mensi, M. M., Vignoli, A., Agliardi, C., Zanette, M., & Clerici, M.
Affiliations
  • Don Carlo Gnocchi Foundation (IT)
  • Fondazione Istituto Neurologico Nazionale Casimiro Mondino (IT)
  • University of Bologna (IT)
  • University of Milan (IT)
Corresponding author
Guerini, Franca R.
Venue
Brain, Behavior, and Immunity
Publisher
Elsevier BV
Published
2015-02
Volume
44
Pages
207-212
ISSN
0889-1591 (ISSN-L)
OpenAlex
W2043345370
Cited by
39
References
52
Citations by year
2025: 2 · 2024: 5 · 2023: 6 · 2022: 1 · 2021: 5 · 2020: 3 · 2019: 3 · 2018: 3 · 2017: 5 · 2016: 3 · 2015: 3
FWCI
2.04
Type
journal article
Language
en
Open access
closed
Locations
  • Brain Behavior and Immunity (publishedVersion)
  • PubMed (publishedVersion)
Funders
Italian Ministry of Health
Topics
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
  • Life Sciences › Immunology and Microbiology › Immunology › Reproductive System and Pregnancy
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
Keywords
HLA-G, 14 bp insertion/deletion polymorphism, autism spectrum disorder, prenatal immune activation, maternal-fetal immune tolerance, KIR ligands, natural killer cells, soluble HLA-G, 3' untranslated region, maternal-fetal interface
MeSH terms
Adolescent, Adult, Child, Child Development Disorders, Pervasive, Female, Genotype, Humans, Italy, Male, Middle Aged, Polymorphism, Genetic, Cohort Studies, 3' Untranslated Regions, INDEL Mutation, HLA-G Antigens

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