Autism is generally believed to be a behavioral syndrome that includes
abnormalities of language and thinking skills; repetitive behavior such as
rocking; abnormal responses to sensations, people, events and objects; and
self- injurious behavior. What causes the syndrome is not known. A few years
ago, we hypothesized that one possible cause of autism may involve faulty
immune regulation, in particular, autoimmunity ( 1,2 ).
To further
understand the role of immune factors, we have recently studied immune
response ( or antibodies ) to myelin basic protein ( MBP ), which is a
protein component of the brain myelin. The myelin is a covering sheath that
is necessary for the normal flow of nerve impulses from one nerve cell to
another, and defects in this function would dramatically alter brain
activity and behavior.
In this study, the testing of 33 autistic children
( less than 11 years of age ) was compared with that of 18 age-matched
normal children. The diagnosis of autism was made by at least one
pediatric psychiatrist and one clinical child psychologist using the
DSM-III-R guidelines of the American Psychiatric Association, Washington,
D.C. Since nearly 60% of autistic children show mental retardation
( MR IQ of 70 or lower ), 20 children with MR due to unknown causes and 12
children with Down syndrome ( DS ) were also studied as the disease
controls.
From each donor a 5 ml blood sample was drawn and the serum
separated from the blood cells. The testing for serum antibodies to MBP was
performed with the technique of protein-immunoblotting. When the serum
contained antibodies to MBP, a positive reaction was seen by a protein band.
Screening for these antibodies showed that they were found in 19 of 33
( 58% ) sera from autistic children as compared to only 7 of 50 ( 7% ) sera
from the control children.
This result indicated that the autistic children
have about 8.3 times greater incidence of antibodies to MBP than the control
children. Since none of the 12 DS children and only 3 of 20 MR children
showed this antibody- positive reaction, it may be concluded that the mental
retardation in autistic children is not related to the production of
antibodies to MBP.
Immunological testing of autistic children has shown certain FEATURES that
are also found in patients with autoimmune diseases such as systemic lupus
erythematosus ( SLE ), thyroid disease ( TD ), ankylosing spondylitis
( AS ), rheumatoid arthritis ( RA ), insulin-dependent diabetes ( IDD ), and
multiple sclerosis ( MS ).
These are:
( a ) genetic predisposition-autism
shows a greater concordance rate in monozygotic twins than in the normal
population;
( b ) gender factor-autism is 4 or 5 times more common in boys
than in girls;
( c ) triggering by microorganisms-rubella virus and
cytomegalovirus infections have been indirectly linked to autism;
( d ) maternal factors-maternal antibodies in autism were detected by us ( 3 );
( e ) major histocompatibility ( MHC ) association- autism displays genetic
linkage with immunogenetic factors located on chromosome 6, as recently
discovered by our group ( 4 ); and
( f ) immune activation-this was recently observed by us in autism ( 5 ).
Taken collectively, the aforementioned
parallels between autism and other autoimmune diseases suggest that
autoimmunity may be a critical factor in the cause of autism. An essential
part of the autoimmune mechanism should involve antibody-mediated immune
response or antibodies against brain, the affected organ in autism. In this
respect, a few recent studies in autism have found evidence of antibodies to
brain tissue antigens, e.g., MBP ( this report ), neurofilament proteins ( 2 ),
and serotonin receptor ( 6 unpublished data ).
Antibodies to MBP
may have some pathological relevance since abnormal cell-mediated immune
response ( involving a soluble factor but not antibodies ) to this protein
was previously detected by another group of researchers ( 7 ),
suggesting that autistic children somehow develop inappropriate immune responses to
this brain protein. Brain-reactive antibodies and the increased serum levels
of IgG3 antibody ( 8 ),
which selectively activates complement function via
classical pathway ( another type of immunity ), could be an important first
step in the activation of complement-mediated nerve cell damage, thereby
altering their ability to perform normal function of nerve impulse
transmission. Despite numerous behavioral problems, research into the brains
of autistic children has been hampered by the lack of available brain
biopsies or autopsies. Based on a very limited number of case studies,
anatomical abnormalities in certain parts of the brain have been found, but
the findings are not suffiently consistent to permit any firm conclusion.
While the pathological data are scarce, we know virtually nothing about the
neurochemistry ( neurotransmitter function ) of the autistic brain. Whatever
the pathological abnormalities might be, it is generally believed that the
anatomical defects are the results of abnormal development rather than
damage following full development of the brain in autistic children ( 9 ).
At present, the relationship between antibodies to MBP and autism is not
understood. However, we hypothesize that the development of this immune
response may be the basis of autoimmune pathogenesis in some cases of
autism. At birth, there is very little myelin in the brain, and the
synthesis of myelin may not be complete until the age of 10 years or older
in the normal child ( 10 ). Moreover,
It has been suggested that some children with learning disabilities
( LD ) may have delayed or incomplete myelin development ( 11 ).
In light of the above, it is conceivable that if
an immunological assault were to occur before birth or during infancy or
childhood, it could lead to poor myelin development or abnormal function of
the nerve fiber myelin. This line of thinking, as we postulate in this
report, may be an important step in the future understanding of the
pathological basis of Autism.
by Vijendra K. Singh, Reed P. Warren, Dennis Odell: Utah State Univ, 1992 |
Autism Info