Front Matter

240 Maternal Antibodies to Fetal Brain Neurons and Autism

sites are protected from the immune system. Hence, we regularly implant cornea

from the eye. Many of us agree to allow our corneas to be donated; this is

often done when the driver’s license is obtained. Similarly, human testis can be

transplanted with minimum rejection. The main reason for the unusual nature

of immunological privileged sites is that the antigens in the brain, testes, and eyes

appear after the constitution of self‐tolerance (i.e., germ cells) or are sealed

during the fetal development by specialized barriers (e.g., BBB, Sertoli‐blood

barrier and vitreous‐humor barrier, for the testis, brain and eye, respectively).

These so called neo‐antigens are sequestered from the early stages of immune

development where the “self‐recognition” process takes place. Of course, this is

the simplest way this highly complex concept can be described; it is beyond the

scope of this book for us to describe this concept further. Readers are invited to

refer to the literature to explore this topic in more detail [11,12] (Figure 8.3).

Neuroantigens/Abs

LDHA/B

STIPl

CRMPl

OTR

AVPR

Immune

system

Dendritic

cells

Migration

to the CNS

Protective

(destructive)

Neurodegeneration

Immune response to

released antigens from

fetal brain

Figure 8.3 An autoimmune hypothetical model of the immunopathogenesis of ASD: The role

of the immune system in a primary neurodegenerative scenario. The figure illustrates the

molecular and immunological mechanism by which autoimmunity can play a role in development

of ASD. The middle section shows the leakage of selective brain antigens passing through the

placental barrier (green). Top left shows antibodies to the leaked fetal neroantigens (i.e., LDH,

YBX1, cypin, STIP1, CRMP1 and CRMP2) from the brain after an environmental injury. The

maternal adaptive immune system develop antibodies to these neuroantigens and maternal

autoantibodies cross the feto‐amniotic barrier (shown in green) and enters the brain, causing

damage to the fetal brain only in selected areas. (See insert for color representation of this figure.)