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
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
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.