Fwd: Some Cases Of Autism May Be Traced To The Immune System

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Some Cases Of Autism May Be Traced To The Immune System Of Mothers

During Pregnancy

ScienceDaily (Feb. 11, 2008) & mdash;

http://www.sciencedaily.com/releases/2008/02/080211172535.htm

New research from the UC M.I.N.D. Institute and Center for

Children's Environmental Health has found that antibodies in the

blood of mothers of children with autism bind to fetal brain cells,

potentially interrupting healthy brain development. The study authors

also found that the reaction was most common in mothers of children

with the regressive form of autism, which occurs when a period of

typical development is followed by loss of social and/or language

skills. The findings raise the possibility that the transfer of

maternal antibodies during pregnancy is a risk factor for autism and,

at some point, that a prenatal test and treatment could prevent the

disorder for some children.

" While a growing body of research is dedicated to finding

distinctions in the immune systems of children with autism, this is

one of the first studies to identify immunological factors in mothers

that could be linked to autism in the very earliest stages of life, "

said Judy Van de Water, senior author of the study and professor of

rheumatology, allergy and clinical immunology. " Our results should

lead to more research on the prenatal environment and the onset of

autism. We are also optimistic that in the future a prenatal test and

therapeutic intervention preventing IgG exposure during pregnancy

could protect some children from ever getting autism. "

Van de Water and her team began their research with blood samples

from 123 mothers -- 61 whose children have autism and 62 whose

children are typically developing. They isolated IgG antibodies from

the samples then exposed the antibody to fetal brain tissue by

western blot analysis, which detects antibody reactivity to proteins.

The outcome revealed a highly specific reactivity pattern to two fetal

brain proteins in seven of the 61 samples from the autism group, six

of which were from mothers of children who had regressive autism.

None of the IgG samples from mothers in the control group produced

this same result.

" We're not entirely sure why the IgG response against fetal brain

proteins was so specific for later onset autism, " said Van de Water.

" It's possible that early exposure to maternal antibodies sets in

motion a biological path to autism with the behavioral outcomes not

apparent until much later. It's also possible that an environmental

exposure sometime after birth could be required to set this process

in motion. We are hopeful that this study will help build our

understanding of the foundations of the regressive form of the

disorder. "

Characteristic features of autism -- social deficits, language

impairments and limited, repetitive behaviors -- are often clear

early in an affected child's life. Other children seem to progress

normally until 12-to-24 months of age, when developmental milestones

disappear. These distinct pathways have led clinicians to identify

autism as one of two types -- early onset or regressive --

potentially with distinct causes and disease processes.

IgG antibodies are responsible for long-term immune system responses

to infection, but they can also contribute to autoimmune diseases

such as arthritis, multiple sclerosis and lupus. IgG also crosses the

placenta in order to provide key immune system protectants to a

growing fetus and newborn child, which is a key reason why Van de

Water decided to investigate the role of IgG as a potential factor in

autism.

Van de Water next wants to know if IgG in women during the time of

their pregnancies produces the same response to fetal brain proteins.

Women in the current study were two-to-five years beyond childbirth.

She will now conduct the same study with women who are pregnant and

already have a child with autism, because such women are much more

likely to have another child with the disorder.

" If women in this next phase of the study give birth to a child

eventually diagnosed with autism, blood analyses from all stages of

her pregnancy will give us a clear picture of the immune system

factors that were in play during gestation and could have altered her

child's neurodevelopment, " Van de Water said.

Other key next steps are to identify the specific proteins targeted

by autism-specific maternal antibodies and their role in

neurodevelopment and to determine whether or not exposure to maternal

IgG during pregnancy leads to behavioral or social distinctions in

offspring. Animal model studies are now under way to help answer

these questions.

" Our outcome leads autism science in many new and exciting

directions, " said Braunschweig, pre-doctoral fellow of

immunology in the Van de Water lab, lead author of the current study

and recent recipient of an Autism Speaks mentor fellowship to further

pursue this research. " We now know we should be looking for the clues

to the onset and pathology of autism much earlier than was initially

assumed. Future studies should consider the immune system

interactions between mother and child as a focal point in creating

greater understanding of, and eventually finding effective

preventions for, this complex neurodevelopmental disorder. "

" This finding is important because it provides important clues about

the potential maternal contributions to autism risk in a subset of

children who may develop autism, " said Isaac Pessah, director of the

UC Center for Children's Environmental Health and professor of

molecular biosciences. " We're determined to find out what causes

autism. Studies conducted in the Van de Water lab are giving us

valuable insights as to when and where in the developmental process

we should be looking for those causes. "

" We're very interested in understanding the underlying causes of

autism, " said Lawler, scientific program director at the

National Institute of Environmental Health Sciences. " This finding,

in combination with other new research findings coming from

NIH-funded studies, demonstrates the complexity of this disorder and

underscores the importance of understanding how the mother's immune

system can influence early brain development. "

The study, " Maternally Derived Antibodies Specific for Fetal Brain

Proteins, " is to be published in the March 2008 issue of

Neurotoxicology. It was funded by the National Institutes of

Environmental Health Sciences, the U.S. Environmental Protection

Agency and the M.I.N.D. Institute.

Adapted from materials provided by University of California - -

Health System, via EurekAlert!, a service of AAAS.

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