MATERNAL INFECTION AND AUTISM Hatf Sohail, Sama El Refaei, Alexander Yong, Vaishali Sri Prathap PHM142 Fall 2015 Coordinator: Dr. Jeffrey Henderson Instructor: Dr. David Hampson

WHAT IS AUTISM SPECTRUM DISORDER (ASD)? Impairments in social interactions, communication, and a stereotyped, repetitive repertoire of interests and activities Considered a spectrum because of the variety of symptoms and varying degrees of severity There is a connection between ASD and low immunoglobulin counts Higher prevalence in boys Picture Taken from: "The Signs of Autism in Toddlers: How to Spot Autism in Children." Health Guide Info. Web. 13 Oct

Dysregulation in the cytokines in the CSF of autistic child are so elevated Leads to impaired communication and aberrant behaviours The elevation of cytokine IL-6 is essential for development of the abnormal behaviors and changes in brain gene expression in the offspring. Blocking IL-6 prevents the development of these aberrant behaviors. The elevation of cytokine IL-10 also protects against MIA. Increased IL-10 can lead to behavioral abnormalities in the adult offspring.

Picture taken from: Patterson, Paul H. "Maternal infection and immune involvement in autism."Trends in molecular medicine 17.7 (2011):

Proposed pathways about how MIA may lead to developmental abnormalities: Cytokines of maternal origin cross the placenta and act on the fetal central nervous system MIA induces a placental inflammatory state leading to placental cytokine secretion which can pass to the fetus MIA triggers a fetal inflammatory response

Viral infection → elevated cytokine and antibody levels → cross placenta → disrupt fetal neurodevelopment Taken from: "Placenta." Wikipedia. Wikimedia Foundation. Web. 13 Oct

Strong association with maternal viral infection in the first trimester Significant association with maternal bacterial infection during hospital admission in the second and third trimester. Picture taken from: ("What Is: A Trimester?" PHI Center. Web. 13 Oct )

Viral infections Influenza Viral gastroenteritis Congenital cytomegalovirus Perinatal herpes simplex virus Congenital rubella Bacterial infections Urinary tract infection Genital infection including STDs Respiratory infections. Mycosal Infections

Summary Slide ASD children have low immunoglobulins, low T cell numbers, altered cytokine profiles, low-normal functioning and low NK cells Dysregulation in cytokines causes elevated levels in the CSF of the child Elevation of the proinflammatory cytokine IL-6 changes brain gene expression in offspring; blocking IL-6 during MIA prevents the aberrant behaviors; elevation of the anti-inflammatory cytokine IL-10 also protects against MIA. Changes in endocrine factors probably lead to acute placental pathophysiology and subsequent effects on fetal development. Persistent viral infections could lead to chronically elevated cytokine/antibody levels in the body that cross the placenta, cross-reacts with molecules containing sialic acid epitopes via molecular mimicry Strong association with maternal viral infection in the first trimester and maternal bacterial infection second/third trimester Common viral infections include: influenza, viral gastroenteritis, congenital cytomegalovirus, perinatal herpes simplex virus, and con-genital rubella Common Bacterial infections include: bacterial infections are urinary tract infection and genital infection including STDs, and respiratory infections

References Atladóttir, Hjördis O., et al. "Maternal infection requiring hospitalization during pregnancy and autism spectrum disorders." Journal of autism and developmental disorders (2010): "Immune Function & ASD | Autism Research Institute." Immune Function & ASD | Autism Research Institute. N.p., n.d. Web. 11 Oct Patterson, Paul H. "Maternal infection and immune involvement in autism."Trends in molecular medicine 17.7 (2011): Zerbo, Ousseny, et al. "Maternal infection during pregnancy and autism spectrum disorders." Journal of autism and developmental disorders (2013): 1-11.