The activity of natural killer (NK) cells is modulated by the interaction between killer-cell immune globulin-like receptor (KIR) proteins and their cognate HLA ligands; activated NK cells produce inflammatory cytokines and mediate innate immune responses. Activating KIR/HLA complexes (aKIR/HLA) were recently suggested to prevail in children with autism spectrum disorders (ASD), a neurodevelopmental syndrome characterized by brain and behavioral abnormalities and associated with a degree of inflammation. We verified whether such findings could be confirmed by analyzing two sample cohorts of Sardinian and continental Italian ASD children and their mothers. Results showed that aKIR/HLA are increased whereas inhibitory KIR/HLA complexes are reduced in ASD children; notably this skewing was even more significant in their mothers. KIR and HLA molecules are expressed by placental cells and by the trophoblast and their interactions result in immune activation and influence fetal, as well as central nervous system development and plasticity. Data herein suggest that in utero KIR/HLA immune interactions favor immune activation in ASD; this may play a role in the pathogenesis of the disease.

Activating KIR molecules and their cognate ligands prevail in children with a diagnosis of ASD and in their mothers / F. Guerini, E. Bolognesi, M. Chiappedi, S. Manca, A. Ghezzo, C. Agliardi, M. Zanette, R. Littera, C. Carcassi, S. Sotgiu, M. Clerici. - In: BRAIN BEHAVIOR AND IMMUNITY. - ISSN 0889-1591. - 36(2014 Feb), pp. 54-60.

Activating KIR molecules and their cognate ligands prevail in children with a diagnosis of ASD and in their mothers

C. Agliardi;M. Clerici
2014-02

Abstract

The activity of natural killer (NK) cells is modulated by the interaction between killer-cell immune globulin-like receptor (KIR) proteins and their cognate HLA ligands; activated NK cells produce inflammatory cytokines and mediate innate immune responses. Activating KIR/HLA complexes (aKIR/HLA) were recently suggested to prevail in children with autism spectrum disorders (ASD), a neurodevelopmental syndrome characterized by brain and behavioral abnormalities and associated with a degree of inflammation. We verified whether such findings could be confirmed by analyzing two sample cohorts of Sardinian and continental Italian ASD children and their mothers. Results showed that aKIR/HLA are increased whereas inhibitory KIR/HLA complexes are reduced in ASD children; notably this skewing was even more significant in their mothers. KIR and HLA molecules are expressed by placental cells and by the trophoblast and their interactions result in immune activation and influence fetal, as well as central nervous system development and plasticity. Data herein suggest that in utero KIR/HLA immune interactions favor immune activation in ASD; this may play a role in the pathogenesis of the disease.
Autism ; HLA ligands ; Human leukocyte antigens ; Killer cell immunoglobulin-like receptor ; Kir genes ; Maternal immunity ; Natural killer cells
Settore MED/04 - Patologia Generale
Article (author)
File in questo prodotto:
Non ci sono file associati a questo prodotto.
Pubblicazioni consigliate

Caricamento pubblicazioni consigliate

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: http://hdl.handle.net/2434/245098
Citazioni
  • ???jsp.display-item.citation.pmc??? 13
  • Scopus 23
  • ???jsp.display-item.citation.isi??? 20
social impact