An HLA-G∗14bp insertion/deletion polymorphism associates with the development of autistic spectrum disorders
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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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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Fang, C., Sun, Y., Fan, C., & Lei, D. (2024) · Figshare · doi:10.6084/m9.figshare.26740154
Fang, C., Sun, Y., Fan, C., & Lei, D. (2024) · Figshare · doi:10.6084/m9.figshare.26122859
Fang, C., Sun, Y., Fan, C., & Lei, D. (2024) · Figshare · doi:10.6084/m9.figshare.26740142
Fang, C., Sun, Y., Fan, C., & Lei, D. (2024) · Figshare · doi:10.6084/m9.figshare.26740175
Fang, C., Sun, Y., Fan, C., & Lei, D. (2024) · Figshare · doi:10.6084/m9.figshare.26122720
Fang, C., Sun, Y., Fan, C., & Lei, D. (2024) · Figshare · doi:10.6084/m9.figshare.26740151
Fang, C., Sun, Y., Fan, C., & Lei, D. (2024) · Figshare · doi:10.6084/m9.figshare.26740178
Fang, C., Sun, Y., Fan, C., & Lei, D. (2024) · Figshare · doi:10.6084/m9.figshare.26740145
Fang, C., Sun, Y., Fan, C., & Lei, D. (2024) · Figshare · doi:10.6084/m9.figshare.26740148
Fang, C., Sun, Y., Fan, C., & Lei, D. (2024) · Figshare · doi:10.6084/m9.figshare.26740166
Fang, C., Sun, Y., Fan, C., & Lei, D. (2024) · Figshare · doi:10.6084/m9.figshare.26740139
Fang, C., Sun, Y., Fan, C., & Lei, D. (2024) · Figshare · doi:10.6084/m9.figshare.26740160
Fang, C., Sun, Y., Fan, C., & Lei, D. (2024) · Figshare · doi:10.6084/m9.figshare.26740157
- 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.
- ORCID
- 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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