242 Maternal Antibodies to Fetal Brain Neurons and Autism
Since the encroachment of the neo‐chemicals, many investigators also have
been noticing the negative role of the maternal immune system and potential
presence of anti‐brain antibodies [13,14].
In 1990, Warren et al. [15] noticed a connection between ASD and maternal
autoantibodies that reacted to proteins displayed on the fathers’ immune cells,
found predominantly in women with a history of miscarriage. These antibodies
were suspiciously more common in mothers with children with ASD. This
seminal study aroused further investigation and Dalton et al. [16] were able to
show that a single sample from the serum of a mother with a child with ASD
reacted to mouse neurons resulting in deficits in the exploratory behaviors in
the resulting offspring when injected into a dam during gestation.
Here we would like to define a type of antibody called IgG. In humans and
other mammals, antibodies come in different forms (i.e., IgD, IgM, IgA, IgE,
and IgG). IgG is the most abundant in human blood, plasma, and serum. IgG
maternal antibodies readily cross the placenta to the fetus. These antibodies
are highly beneficial to the newborns and serve as a protection against numer
ous possible infectious agents [10,11]. These maternal IgG antibodies persist in
newborns for up to 6 months after birth [11]. However, along with protective
IgG antibodies, neuroantibodies can react to fetal “neuroantigens,” which can
cross the placenta and cause damage to a developing fetal brain, if the mother
has developed neuroantibodies to the fetal brain.
Some of the most outstanding and elegant research studies were carried
out by Braunschweig et al. [17,18] who analyzed 61 children with autism and
62 normotypic (normal) children, along with their mothers, and uncovered
potential neuroantibodies in autistic children. Maternal antibodies that were
present in 10% of the pregnant women were found to recognize certain anti
gens in the developing fetal brain cells. An important aspect of the study was
the understanding of the role of the BBB during fetal development. Western
blot analysis revealed that maternal antibodies (IgG) reacted with fetal proteins
(i.e., LDH, YBX1, cypin, STIP1, CRMP1, and CRMP2) and thus could adversely
affected fetal neurodevelopment, since the BBB is permeable to the maternal
IgG throughout the gestational period [11,18–20]. This study showed a signifi
cant correlation between the paired maternal antibody reactive to fetal brain
neuroantigens located within the 37‐ and 73‐kDa molecular‐weight bands on a
human fetal brain immunoblot and a diagnosis of ASD in the child. Further,
this reactivity was observed only in plasma samples obtained from families
affected with ASD and not in families that had normal children or children
diagnosed with developmental delay. This appears to play an important role in
certain cases of ASD. The research suggests that over 50% of the mothers of
children with ASD showed reactivity in relation to neuroantigens [17,18]. This
hypothesis was further validated by utilizing the Rhesus monkey model [19,20].
Infusion of these neuroantibodies into the pregnant Rhesus monkeys showed
that various combinations of neuroantibodies infused into the pregnant