MATERNAL INFECTION AND AUTISM

Hatf Sohail, Sama El Refaei, Alexander Yong, Vaishali Sri Prathap

PHM142 Fall 2015Coordinator: Dr. Jeffrey HendersonInstructor: 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. 2015. <http://www.healthguideinfo.com/diagnosing-autism/p76634/#imgn_0>

• 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): 389-394.

• 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. 2015.<https://en.wikipedia.org/wiki/Placenta#/media/File:Placenta.svg>

• 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. 2015. <http://kabariyahospital.weebly.com/uploads/3/8/1/2/3812796/1472675.gif?585>)

• 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 40.12 (2010): 1423-1430.

"Immune Function & ASD | Autism Research Institute." Immune Function & ASD | Autism Research Institute. N.p., n.d. Web. 11 Oct. 2015.

Patterson, Paul H. "Maternal infection and immune involvement in autism."Trends in molecular medicine 17.7 (2011): 389-394.

Zerbo, Ousseny, et al. "Maternal infection during pregnancy and autism spectrum disorders." Journal of autism and developmental disorders (2013): 1-11.