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.

Guerini, F., Bolognesi, E., Chiappedi, M., Ghezzo, A., Canevini, M., Mensi, M., Vignoli, A., Agliardi, C., Zanette, M., Clerici, M., An HLA-G∗14bp insertion/deletion polymorphism associates with the development of autistic spectrum disorders, <<BRAIN BEHAVIOR AND IMMUNITY>>, 2015; 44 (Febbraio): 207-212. [doi:10.1016/j.bbi.2014.10.002] [http://hdl.handle.net/10807/66404]

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

Zanette, Michela;
2015

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.
Inglese
Guerini, F., Bolognesi, E., Chiappedi, M., Ghezzo, A., Canevini, M., Mensi, M., Vignoli, A., Agliardi, C., Zanette, M., Clerici, M., An HLA-G∗14bp insertion/deletion polymorphism associates with the development of autistic spectrum disorders, <<BRAIN BEHAVIOR AND IMMUNITY>>, 2015; 44 (Febbraio): 207-212. [doi:10.1016/j.bbi.2014.10.002] [http://hdl.handle.net/10807/66404]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10807/66404
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