Mom’s antibodies to herpes simplex virus 2 tied to autism in male offspring

By Will Boggs MD

NEW YORK (Reuters Health) - Increased levels of maternal antibodies to herpes simplex virus 2 (HSV-2) in midpregnancy are associated with an elevated risk of autism spectrum disorder (ASD) in male offspring.

A variety of infections during pregnancy have been implicated in several neurodevelopmental disorders, including ASD, suggesting that general, nonspecific immune activation, rather than a specific pathogen, may be involved.

Dr. W. Ian Lipkin from Columbia University Mailman School of Public Health in New York City and colleagues investigated the possible association between maternal exposure to ToRCH pathogens (Toxoplasma gondii, rubella virus, cytomegalovirus (CMV), and herpes simplex viruses 1 (HSV-1) and 2 (HSV-2)) during pregnancy and the risk of ASD in their offspring.

Maternal seropositivity rates to any of the pathogens at midpregnancy and postpartum did not differ significantly between 442 mothers of ASD children and 464 mothers of control children, the team reports in mSphere, online February 22.

However, levels of IgG antibodies to HSV-2 were significantly higher in midpregnancy samples from mothers of boys with ASD, compared with control mothers.

An anti-HSV-2 level of 640 AU/mL was associated with an ASD risk 2.07-fold higher than a level of 240 AU/mL (p=0.03), the researchers say.

Only a small number of women had high levels of antibodies indicative of recent infection.

“Our findings are consistent with experimental data from mouse models of gestational infection wherein vulnerability of offspring to neurodevelopmental damage depends on timing of the infection of the maternal host and associated activation of the prenatal innate immune system,” the researchers note.

“Epidemiological data suggest that activation of the maternal immune system during early to midpregnancy is associated with long-term developmental brain and behavioral abnormality in the offspring,” they add.

“We speculate that ASD risk associated with high levels of antibodies to HSV-2 is not specific to HSV-2 but instead reflects the impact of immune activation and inflammation on a vulnerable developing nervous system,” they conclude. “The replicability of these findings should be tested in other cohorts given the potential implications for serological monitoring of HSV-2 infections and opportunities for implementation of suppressive therapy during pregnancy.”

The authors add, “Broader serosurveys should also be implemented to examine whether other infectious agents have similar impacts on the incidence of neurodevelopmental disorders.”

Dr. Asher Ornoy from Hadassah Medical School at Hebrew University Jerusalem in Israel, who recently reviewed genetic syndromes, maternal diseases, and antenatal factors associated with ASD, told Reuters Health by email, “We indeed believe that inflammation of the fetal brain is a cause, apparently associated with inflammatory cytokines affecting the fetal brain. Hence, there are no surprising findings in this study. Indeed, the authors are cautious and only recommend more studies.”

“To my opinion, this is an interesting study that should be repeated in other places and also include IgM antibody studies as a marker for possible primary infection with HSV,” he said. “Unless the study is repeated with similar results, I do not think that there are specific clinical implications.”

Dr. Ivan Gentile from the University of Naples “Federico II” in Italy, who earlier found similar seropositivity rates and anti-HSV-1/2 levels in patients with autism and controls, told Reuters Health by email, “The most interesting finding of this paper is the association between high titres of anti-HSV-2 antibodies during pregnancy and the chance of developing ASD in male offspring. However, these results do not indicate a cause-effect relationship.”

“This study confirms that an immunological imbalance can occur during pregnancy of mothers who give birth to children with ASD,” he said. “However, the actual trigger of these immunological events remains unknown.”

“Studies on the etiopathogenesis of ASD are needed,” Dr. Gentile concluded. “This and other studies on this topic can prompt other investigators to assess the role of immunological disturbances and viral reactivations as cofactors in the etiology of ASD in larger controlled studies.”

Dr. Lipkin did not respond to a request for comments.

SOURCE: http://bit.ly/2lOhoKU

mSphere 2017.

(c) Copyright Thomson Reuters 2017. Click For Restrictions - http://about.reuters.com/fulllegal.asp