Association of Maternal HSV-2 Antibodies and Autism Spectrum Disorder Risk
Autism spectrum disorder (ASD) has no known single cause, and its growing incidence has led many researchers to study its influencing factors. While claims of vaccine relatedness are outright false, there are other variables that may contribute to a propensity toward ASD development, including environmental factors, genetic factors, and maternal immune responses. A new mSphere study adds to the latter category, finding an association between pregnant women with herpes simplex virus type 2 (HSV-2) infection and the risk of ASD in their children.
Women (and men) with HSV-2 never clear the virus; rather, the virus remains in a quiescent, nonreplicative form after an initial acute infection. Flare-ups occur when the virus begins replicating again, and both these flare-ups and the initial acute infection lead to production of HSV-specific antibodies as part of the immune response. These HSV-specific antibodies are what were found to be associated with risk of ASD in the sons of previously infected mothers .
The research team, led by first author Milada Mahic and senior scientist W. Ian Lipkin, looked at maternal antibodies to several pathogens associated with miscarriage. There was no association between risk of ASD and the immunoglobulin G response to Toxoplasma gondii, rubella virus, cytomegalovirus, or HSV-1 (these are part of the ToRCH complex, a group of pathogens that can be passed from mother to fetus). However, high levels of HSV-2 antibodies in pregnant women were associated with a higher risk of ASD in their sons.
Unlike the pathogen itself, these maternal antibodies are able to cross the placental barrier. “If herpes were to cross the placenta and get to the fetus, [the fetus] would most certainly die,” says Lipkin. The team thinks the response to HSV-2 infection is one of many that may influence fetal development of ASD. “I think it’s going to be increasingly important to look at ways in which women become exposed to infectious agents during pregnancy and find ways we can modify the immune response to minimize the risk to the fetus,” he adds.
How antibodies to HSV-2 or other infectious agents may influence that risk is unknown; antibodies may cross the placenta to interact with the fetus itself, or may influence the cytokines to which the fetus is exposed. The antibodies were collected from maternal blood samples taken either midpregnancy or after delivery, and most antibody levels were consistent with latent (not actively replicating) viral infection.
The difference in risk to sons versus daughters may be due to the subject selection process. Subjects were selected from the Autism Birth Cohort, a subset of the Norwegian Mother and Child Cohort Study. Children with ASD were identified for the Autism Birth Cohort through questionnaire screening at ages 3, 5, and 7. There were fewer girls than boys with ASD in this group, so a sex-specific effect will need a larger study for confirmation. ASD does affect more boys than girls, which may explain why the number of ASD girls in the cohort was smaller to begin with.
While the results must be repeated, the finding that specific maternal antibodies may increase ASD risk have important implications in risk prevention. Most maternal antibodies cause no harm to the developing fetus, and in fact are important for protection since the immune system takes years to fully mature after birth. But as scientists systematically associate different maternal infections and immune responses with ASD, finding ways to prevent these specific responses from crossing into the fetus may be a future method to mitigate this risk.