Different isoforms of HLA-G protein are endowed with a differential ability to induce allogenic tolerance during pregnancy. As prenatal immune activation is suggested to play a role in the onset of autistic spectrum disorders (ASD), we evaluated HLA G*01:01-*01:06 allelic polymorphism in a cohort of Italian children affected by ASD (N=111) their mothers (N=81), and their healthy siblings (N=39). DNA sequencing analysis of HLA-G exon 2, 3 and 4 was used to obtain HLA-G allelic frequencies; alleles distribution was compared with that of two control groups of Caucasoid couples of multiparous women and their partners from Brazil and Denmark. HLA-G distribution was significantly different in ASD children compared to both control groups (Brazilian pc=1x10-4; Danish pc=1x10-3). Since HLA-G distribution was similar in the two control groups, their data were pooled. Results indicated that HLA-G*01:01 was significantly less frequent (pc=1x10-4; OR:0.5, 95%CI: 0.3-0.7) whereas HLA-G*01:05N was significantly more frequent (pc=2x10-3; OR:7.3, 95%CI: 2.4- 26.6) in ASD children compared to combined controls. Finally, no clear pattern emerged when HLA-G allelic distribution was analyzed in healthy sibs. Notably, HLA-G allelic distribution found in ASD mothers was similar to that observed in the control subgroup of women with recurrent miscarriages, whilst it was significantly different compared to women without miscarriages (pc=6x10-4 df=12). Since HLA-G*01:01 is associated with the elicitation of KIR-mediated tolerogenic responses and HLA-G*01:05N correlates with NK cells activation, results herein indicate that an immune activating milieu during pregnancy is more likely observed in association with the development of ASD, similarly to what occurs in women with recurrent miscarriages

HLA-G coding region polymorphism is skewed in autistic spectrum disorders / Guerini, Fr; Bolognesi, E; Chiappedi, M; Ripamonti, E; Ghezzo, A; Zanette, M; Sotgiu, S; Mensi, Mm; Carta, A; Canevini, Mp; Zanzottera, M; Agliardi, C; Costa, As; Balottin, U; Clerici, M. - In: BRAIN BEHAVIOR AND IMMUNITY. - ISSN 0889-1591. - 67:(2018), pp. 308-313. [10.1016/j.bbi.2017.09.007]

HLA-G coding region polymorphism is skewed in autistic spectrum disorders

Sotgiu S;Carta A;
2018

Abstract

Different isoforms of HLA-G protein are endowed with a differential ability to induce allogenic tolerance during pregnancy. As prenatal immune activation is suggested to play a role in the onset of autistic spectrum disorders (ASD), we evaluated HLA G*01:01-*01:06 allelic polymorphism in a cohort of Italian children affected by ASD (N=111) their mothers (N=81), and their healthy siblings (N=39). DNA sequencing analysis of HLA-G exon 2, 3 and 4 was used to obtain HLA-G allelic frequencies; alleles distribution was compared with that of two control groups of Caucasoid couples of multiparous women and their partners from Brazil and Denmark. HLA-G distribution was significantly different in ASD children compared to both control groups (Brazilian pc=1x10-4; Danish pc=1x10-3). Since HLA-G distribution was similar in the two control groups, their data were pooled. Results indicated that HLA-G*01:01 was significantly less frequent (pc=1x10-4; OR:0.5, 95%CI: 0.3-0.7) whereas HLA-G*01:05N was significantly more frequent (pc=2x10-3; OR:7.3, 95%CI: 2.4- 26.6) in ASD children compared to combined controls. Finally, no clear pattern emerged when HLA-G allelic distribution was analyzed in healthy sibs. Notably, HLA-G allelic distribution found in ASD mothers was similar to that observed in the control subgroup of women with recurrent miscarriages, whilst it was significantly different compared to women without miscarriages (pc=6x10-4 df=12). Since HLA-G*01:01 is associated with the elicitation of KIR-mediated tolerogenic responses and HLA-G*01:05N correlates with NK cells activation, results herein indicate that an immune activating milieu during pregnancy is more likely observed in association with the development of ASD, similarly to what occurs in women with recurrent miscarriages
HLA-G coding region polymorphism is skewed in autistic spectrum disorders / Guerini, Fr; Bolognesi, E; Chiappedi, M; Ripamonti, E; Ghezzo, A; Zanette, M; Sotgiu, S; Mensi, Mm; Carta, A; Canevini, Mp; Zanzottera, M; Agliardi, C; Costa, As; Balottin, U; Clerici, M. - In: BRAIN BEHAVIOR AND IMMUNITY. - ISSN 0889-1591. - 67:(2018), pp. 308-313. [10.1016/j.bbi.2017.09.007]
File in questo prodotto:
File Dimensione Formato  
guerini2017.pdf

accesso aperto

Tipologia: Documento in Post-print (versione referata ma senza layout editoriale)
Licenza: Creative commons
Dimensione 472.2 kB
Formato Adobe PDF
472.2 kB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11388/220364
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 13
  • ???jsp.display-item.citation.isi??? 12
social impact