345 Biomarkers Med. (2014) 8(3), 345–352 ISSN 1752-0363
part of
Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder
characterized by impairments in reciprocal social interactions as well as restricted,
repetitive and stereotyped patterns of behavior. The etiology of ASD is not well
understood, although many factors have been associated with its pathogenesis, such
genetic, neurological, environmental and immunological factors. Several studies have
reported the production of numerous autoantibodies that react with specific brain
proteins and brain tissues in autistic children and alter the function of the attacked
brains tissue. In addition, the potential role of maternal autoantibodies to the fatal
brain in the etiology of some cases of autism has also been reported. Identification
and understanding of the role of brain autoantibodies as biological biomarkers may
allow earlier detection of ASD, lead to a better understanding of the pathogenesis of
ASD and have important therapeutic implications.
Keywords:animalmodels•autism•autoimmunity•brainautoantibodies•BTBR mice
•maternalantibodies•neurodevelopmentaldisorders
Autism spectrum disorder (ASD) is a complex
neurodevelopmental disorder characterized by
impairments in reciprocal social interactions,
such as verbal and nonverbal communication,
and restricted, repetitive and stereotyped pat-
terns of behavior. Recently, the prevalence of
ASD has increased dramatically; the current
prevalence of ASDs is estimated at 1 in 88 chil-
dren, with a male to female ratio of approxi-
mately 5:1 [1] . Patients are typically diagnosed
before the age of 36 months [2] . The etiology
and the clinical expression of the disorder is
heterogeneous and complex [3,4]; multiple fac-
tors have been suggested to be involved in its
pathogenesis such as genetic, environmental,
neurological and immunological factors [5–7] .
There is strong evidence that genetic fac-
tors such as HLADRB1*04 and complement
component C4B can contribute to the patho-
genesis of autism, as well as environmental fac-
tors such as a viral infection that may cause
autoimmunity to the brain and thereby may
lead to pathological changes in the brain of
autistic children [8] .
The potential role of the immune system
in ASD has been addressed in several studies,
especially autoimmunity to CNS. It has been
proposed that autoimmunity may play a key
role in the pathogenesis of neurologic disorders,
including ASD [2,9–12]. These are shown by
several autoimmune factors: presence of brain-
specific autoantibodies; impaired lymphocyte
functions; abnormal cytokine regulation; viral
associations; and indirect association of certain
immunogenetic factors [13], as well as neuroglial
activation and neuroinflammation in the CNS
in autistic children [14]. In addition, a number of
immune system-related genes have been linked
to this disorder. These include the null allele
of the C4B gene, a complement component, as
well as the extended HLA [15–17]. The poten-
tial role for maternal antibodies as a pathogenic
factor has also been proposed [18–20].
Moreover, children with ASD were found
to have a family history of autoimmune dis-
orders, including asthma, multiple sclerosis
(MS), rheumatoid arthritis, Type 2 diabetes
mellitus and celiac disease [2,12,21] . Recently,
Nadra E Elamin
1
& Laila Y AL-Ayadhi*
,1,2
1
AutismResearch&TreatmentCenter,
ShaikAL-AmodiAutismResearch
Chair,FacultyofMedicine,KingSaud
University,Riyadh,SaudiArabia
2
DepartmentofPhysiology,Faculty
ofMedicine,KingSaudUniversity,
POBox2925,Riyadh11461,SaudiArabia
*Authorforcorrespondence:
Tel.:+966114671614
Fax:+9661146207207
ayadh2@gmail.com
Brain autoantibodies in autism spectrum
disorder
Review
10.2217/BMM.14.1 © 2014 Future Medicine Ltd
der