title: Activating KIR molecules and their cognate ligands prevail in children with a diagnosis of ASD and in their mothers.
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.
authors.affiliation: Don C. Gnocchi Foundation, IRCCS, Milano, Italy. Electronic address: fguerini@dongnocchi.it.
authors.forename: Franca R
authors.initials: FR
authors.lastname: Guerini
authors.affiliation: Don C. Gnocchi Foundation, IRCCS, Milano, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Bolognesi
authors.affiliation: Child Neurology and Psychiatry Unit, C. Mondino National Neurological Institute, Pavia, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Chiappedi
authors.affiliation: Unit of Neuropsychiatry for Infants and Adolescents (UONPIA), ASL 1, Sassari, Italy.
authors.forename: Salvatorica
authors.initials: S
authors.lastname: Manca
authors.affiliation: Department of Experimental, Diagnostic, Specialty Medicine, University of Bologna, Associazione Nazionale Famiglie di Persone con Disabilitá Intellettiva e/o Relazionale (ANFFAS), Macerata, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Ghezzo
authors.affiliation: Don C. Gnocchi Foundation, IRCCS, Milano, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Agliardi
authors.affiliation: Don C. Gnocchi Foundation, IRCCS, Milano, Italy.
authors.forename: Michela
authors.initials: M
authors.lastname: Zanette
authors.affiliation: Regional Transplant Center, R. Binaghi Hospital, ASL 8, Cagliari, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Littera
authors.affiliation: Regional Transplant Center, R. Binaghi Hospital, ASL 8, Cagliari, Italy; Medical Genetics, Department of Medical Sciences "Mario Aresu", University of Cagliari, Cagliari, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Carcassi
authors.affiliation: Section of Child Neuropsychiatry, Department of Clinical and Experimental Medicine, University of Sassari, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Sotgiu
authors.affiliation: Don C. Gnocchi Foundation, IRCCS, Milano, Italy; Department of Pathophysiology and Transplantation, University of Milano, Milano, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Clerici
mesh_terms: D002648:Child; D002659:Child Development Disorders, Pervasive / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D006680:HLA Antigens / Q000235:genetics*; D006801:Humans; D008024:Ligands; D008297:Male; D009035:Mothers; D054340:Receptors, KIR / Q000235:genetics*
chemical_list: D006680:HLA Antigens; D008024:Ligands; D054340:Receptors, KIR
keywords: Autism; HLA ligands; Human leukocyte antigens; Killer cell immunoglobulin-like receptor; Kir genes; Maternal immunity; Natural killer cells