title: Autism with intellectual disability is associated with increased levels of maternal cytokines and chemokines during gestation.
abstract: Immune abnormalities have been described in some individuals with autism spectrum disorders (ASDs) as well as their family members. However, few studies have directly investigated the role of prenatal cytokine and chemokine profiles on neurodevelopmental outcomes in humans. In the current study, we characterized mid-gestational serum profiles of 22 cytokines and chemokines in mothers of children with ASD (N=415), developmental delay (DD) without ASD (N=188), and general population (GP) controls (N=428) using a bead-based multiplex technology. The ASD group was further divided into those with intellectual disabilities (developmental/cognitive and adaptive composite score<70) (ASD+ID, N=184) and those without (composite score⩾70) (ASD-noID, N=201). Levels of cytokines and chemokines were compared between groups using multivariate logistic regression analyses, adjusting for maternal age, ethnicity, birth country and weight, as well as infant gender, birth year and birth month. Mothers of children with ASD+ID had significantly elevated mid-gestational levels of numerous cytokines and chemokines, such as granulocyte macrophage colony-stimulating factor, interferon-γ, interleukin-1α (IL-1α) and IL-6, compared with mothers of children with either ASD-noID, those with DD, or GP controls. Conversely, mothers of children with either ASD-noID or with DD had significantly lower levels of the chemokines IL-8 and monocyte chemotactic protein-1 compared with mothers of GP controls. This observed immunologic distinction between mothers of children with ASD+ID from mothers of children with ASD-noID or DD suggests that the intellectual disability associated with ASD might be etiologically distinct from DD without ASD. These findings contribute to the ongoing efforts toward identification of early biological markers specific to subphenotypes of ASD.
authors.affiliation: Division of Rheumatology, Allergy, and Clinical Immunology, Department of Internal Medicine, University of California, Davis, CA, USA.|MIND Institute, University of California, Davis, CA, USA.
authors.forename: K L
authors.initials: KL
authors.lastname: Jones
authors.affiliation: Divison of Research, Kaiser Permanente Northern California, Oakland, CA, USA.
authors.forename: L A
authors.initials: LA
authors.lastname: Croen
authors.affiliation: Divison of Research, Kaiser Permanente Northern California, Oakland, CA, USA.
authors.forename: C K
authors.initials: CK
authors.lastname: Yoshida
authors.affiliation: Division of Rheumatology, Allergy, and Clinical Immunology, Department of Internal Medicine, University of California, Davis, CA, USA.|MIND Institute, University of California, Davis, CA, USA.
authors.forename: L
authors.initials: L
authors.lastname: Heuer
authors.affiliation: MIND Institute, University of California, Davis, CA, USA.|Department of Pediatrics, University of California, Davis, CA, USA.
authors.forename: R
authors.initials: R
authors.lastname: Hansen
authors.affiliation: Divison of Research, Kaiser Permanente Northern California, Oakland, CA, USA.
authors.forename: O
authors.initials: O
authors.lastname: Zerbo
authors.affiliation: Divison of Research, Kaiser Permanente Northern California, Oakland, CA, USA.
authors.forename: G N
authors.initials: GN
authors.lastname: DeLorenze
authors.affiliation: Environmental Health Investigations Branch, California Department of Public Health, Richmond, CA, USA.
authors.forename: M
authors.initials: M
authors.lastname: Kharrazi
authors.affiliation: Stanley Division of Developmental Neurovirology, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: R
authors.initials: R
authors.lastname: Yolken
authors.affiliation: MIND Institute, University of California, Davis, CA, USA.|Department of Medical Microbiology and Immunology, University of California, Davis, CA, USA.
authors.forename: P
authors.initials: P
authors.lastname: Ashwood
authors.affiliation: Division of Rheumatology, Allergy, and Clinical Immunology, Department of Internal Medicine, University of California, Davis, CA, USA.|MIND Institute, University of California, Davis, CA, USA.
authors.forename: J
authors.initials: J
authors.lastname: Van de Water
mesh_terms: D000328:Adult; D000067877:Autism Spectrum Disorder / Q000453:epidemiology / Q000209:etiology; D001321:Autistic Disorder / Q000150:complications / Q000209:etiology*; D016022:Case-Control Studies; D018925:Chemokines / Q000009:adverse effects* / Q000097:blood; D002648:Child; D002657:Child Development; D002659:Child Development Disorders, Pervasive / Q000453:epidemiology / Q000209:etiology; D002675:Child, Preschool; D016207:Cytokines / Q000009:adverse effects* / Q000097:blood; D002658:Developmental Disabilities / Q000150:complications; D005260:Female; D006801:Humans; D007223:Infant; D008607:Intellectual Disability / Q000209:etiology; D008297:Male; D009035:Mothers; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000473:pathology
chemical_list: D018925:Chemokines; D016207:Cytokines