Immune Endophenotypes in Children With Autism Spectrum Disorder.
Autism spectrum disorder (ASD) is characterized by social communication deficits and restricted, repetitive patterns of behavior. Varied immunological findings have been reported in children with ASD. To address the question of heterogeneity in immune responses, we sought to examine the diversity of immune profiles within a representative cohort of boys with ASD.



Peripheral blood mononuclear cells from male children with ASD (n = 50) and from typically developing age-matched male control subjects (n = 16) were stimulated with either lipopolysaccharide or phytohemagglutinin. Cytokine production was assessed after stimulation. The ASD study population was clustered into subgroups based on immune responses and assessed for behavioral outcomes.



Children with ASD who had a proinflammatory profile based on lipopolysaccharide stimulation were more developmentally impaired as assessed by the Mullen Scales of Early Learning. They also had greater impairments in social affect as measured by the Autism Diagnostic Observation Schedule. These children also displayed more frequent sleep disturbances and episodes of aggression. Similarly, children with ASD and a more activated T cell cytokine profile after phytohemagglutinin stimulation were more developmentally impaired as measured by the Mullen Scales of Early Learning.



Children with ASD may be phenotypically characterized based upon their immune profile. Those showing either an innate proinflammatory response or increased T cell activation/skewing display a more impaired behavioral profile than children with noninflamed or non-T cell activated immune profiles. These data suggest that there may be several possible immune subphenotypes within the ASD population that correlate with more severe behavioral impairments.
Department of Medical Microbiology and Immunology, University of California, Davis, Davis, California; MIND Institute, University of California, Davis, Davis, California.
Milo
M
Careaga
MIND Institute, University of California, Davis, Davis, California; Departments of Psychiatry, University of California, Davis, Davis, California.
Sally
S
Rogers
MIND Institute, University of California, Davis, Davis, California; Pediatrics, University of California, Davis, Davis, California.
Robin L
RL
Hansen
MIND Institute, University of California, Davis, Davis, California; Departments of Psychiatry, University of California, Davis, Davis, California.
David G
DG
Amaral
MIND Institute, University of California, Davis, Davis, California; Division of Rheumatology, Allergy and Clinical Immunology, University of California, Davis, Davis, California.
Judy
J
Van de Water
Department of Medical Microbiology and Immunology, University of California, Davis, Davis, California; MIND Institute, University of California, Davis, Davis, California. Electronic address: pashwood@ucdavis.edu.
Paul
P
Ashwood
D000067877:Autism Spectrum Disorder / Q000276:immunology*; D018932:Chemokine CCL2 / Q000276:immunology; D002675:Child, Preschool; D016207:Cytokines / Q000276:immunology*; D058068:Endophenotypes; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000276:immunology*; D007371:Interferon-gamma / Q000276:immunology; D016753:Interleukin-10 / Q000276:immunology; D018793:Interleukin-13 / Q000276:immunology; D053583:Interleukin-1beta / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008070:Lipopolysaccharides; D008297:Male; D010835:Phytohemagglutinins
C111835:CCL2 protein, human; D018932:Chemokine CCL2; D016207:Cytokines; D018793:Interleukin-13; D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; D010835:Phytohemagglutinins; D016753:Interleukin-10; D007371:Interferon-gamma
Autism spectrum disorder; Behavior; Children; Cluster analysis; Cytokine; Endophenotyping; Immune