Maternal HY-restricting HLA class II allele: possible factor involved in brain inflammation of autistic children in utero

Throughout pregnancy, maternal antibodies (IgG) can cross the placenta to provide a passive immunity towards the developing fetus whose immune system is still immature. Placenta allows the passage of maternal antibodies regardless of their effects: protective or deleterious as seen with the maternal antibodies reactive to fetal antigens (autoantibodies) that remain in the infant’s circulation for up to 6 months after birth.

During a first pregnancy with a male fetus, the maternal immune system could be activated by allogenic fetal cells possessing male-specific minor histocompatibility inherited antigens (HYrHLA allele) that are encoded by genes localized on the Y chromosome. In some women, this can lead to an acute immune reaction leading to the production of HY antibodies by B cells that can last for several years in the maternal serum. The activation of the maternal immune system in these patients seems to be correlated with the presence of other underlying immune issues that we find in our patient population.

Although present in 30% of women, anti HY antibodies have been linked to secondary recurrent miscarriage in subsequent pregnancy (male fetus) and other pregnancy complications such as stillbirth, placental abruption or fetal growth retardation, all these events being the results of an inflammatory environment.

Autistic children show a panel of immunological alterations involving cytokines, immunoglobulins, inflammation, and cellular activation. Indeed, maternal autoantibodies that target fetal brain have been detected in the serum and the brain of autistic children and could be involved in brain injuries that play a key role in developmental disorders.

Anti-HY antibodies induce the production of pro-inflammatory cytokines such as TNFα and activate CD8+ T lymphocytes.

Although they have not been yet identified as brain specific maternal autoantibodies involved in autism development, anti-HY antibodies could cross the placenta and the Blood/Brain barrier (BBB) of the immature fetal brain, and ultimately affect its development by inducing a toxic environment that could be responsible for fetal neurodevelopmental impairments.

To date, no studies have looked at the association between anti-HY antibodies and ASD development but we, at Braverman Reproductive Immunology, strongly believe that the inflammation resulting from an anti-HY antibody production could play a role in ASD and this could explain the high prevalence of the syndrome in males.

Send Us an Email

Open Up the Discussion & Share Your Thoughts

Your answers won’t be published and will be used to help us improve our website.

Do you have an autistic child?

Have you been diagnosed with an autoimmune disease or do you think you might be at risk?

Did you learn how maternal health during pregnancy can affect fetal brain development and be involved in ASD in children?

Join Our Discussion Forum

Need more information? Join the discussion today!

What You Need to Know