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.
An HLA-G*14bp insertion/deletion polymorphism associates with the development of autistic spectrum disorders / F.R. Guerini, E. Bolognesi, M. Chiappedi, A. Ghezzo, M.P. Canevini, M.M. Mensi, A. Vignoli, C. Agliardi, M. Zanette, M. Clerici. - In: BRAIN BEHAVIOR AND IMMUNITY. - ISSN 0889-1591. - 44(2015 Feb), pp. 207-212.
|Titolo:||An HLA-G*14bp insertion/deletion polymorphism associates with the development of autistic spectrum disorders|
CLERICI, MARIO SALVATORE (Ultimo)
|Parole Chiave:||Autistic spectrum disorder; Genetic polymorphism; HLA; HLA-G; Immune activation; Immune system; In utero immunology; KIR; NK cells|
|Settore Scientifico Disciplinare:||Settore MED/39 - Neuropsichiatria Infantile|
Settore MED/15 - Malattie del Sangue
|Data di pubblicazione:||feb-2015|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1016/j.bbi.2014.10.002|
|Appare nelle tipologie:||01 - Articolo su periodico|