The immune system in autism (07/2006)
Autism suffers present a widespread range of antibodies against brain tissue and one protein in particular seems to be the major target of these antibodies claim a group of scientists in the July issue of the Journal of Neuroimmunology1. The researchers also show that these antibodies are not genetically determined, as parents of affected individuals do not exhibit them, and so are probably not involved in disease appearance.
Immune abnormalities, including antibodies against the central nervous system, have previously been associated with autism but this is the first study that unequivocally proves such a correlation as earlier findings relied on analyses of a small number of individuals and did not contain appropriate controls.
Autism is a neurodevelopmental syndrome that appears in the first three years of life and affects more boys than girls at a ratio of 3-4:1. The disorder is characterized by socially detached behaviour together with impairment of language and social interaction. Patients tend to have extreme difficulty in learning through experience and consequently adapting their behaviour to respond to life’s changes. The social world and its unpredictability is particularly problematic and can create extreme anxieties exacerbating the disease. Life outcomes range from complete dependence to independent life depending on the intensity of the symptoms and how these were treated from early life.
Autism has various environmental (non-genetic) and genetic influences but the main causes seem to be multiple interacting genetic factors. Environmental factors such as toxic exposures, problems and infections before and after the birth such as rubella and cytomegalovirus seem to account for few cases. Connection to the measles-mumps-rubella (MMR) vaccine, although much talked about, has not been confirmed.
Nevertheless, autism numbers in industrialized societies have increased substantially in the last few years. In the United States, for example, while the disease was relatively rare in the 1990s, recorded numbers have tripled in the last 10 years. In California from 1987 to 1998 the number of children treated for autism has increased by 273%. Although part of this increase might result from better diagnostic tools and increased parental awareness, nevertheless, such an increase within only a decade, seem too extreme to be only attributed to these reasons.
Immune abnormalities together with neurobehavioural symptoms and changes in neurotransmitters are the more solid findings of autism. Understanding the role of each of these components is crucial to one day be able to treat the disorder. But until now the reports on altered immunity although frequent, were never conclusive as experimental conditions tended to be less than perfect.
Susana C. Silva, Catarina Correia and Astrid M. Vicente at the Instituto Gulbenkian de Ciência, Oeiras, Portugal and colleagues studied the blood of a large sample of individuals - 171 patients, 191 parents and 54 healthy controls - and report that autistic patients are in fact characterised by presenting in their blood high levels of non-inherited antibodies against the body’s own brain tissue. Interestingly, they also found that one protein seem to be the main object of the immune attack. The team of scientists isolated and characterised this protein although so far they have not been able to identify it.
These are interesting results that should lead to a better understanding of the disorder. Autism, as mentioned before, is heterogeneous in origin and extremely complex. To improve treatment and prevention it is necessary to recognize, from all the known components of the syndrome, what contributes to the development and symptoms of the disorder and what is consequence of it. What Correia, Vicente and colleagues’ results show is that although an immune dysfunction (auto-antibodies against the brain) does exist in autistic patients, because this is not a hereditary characteristic, it is probably just a secondary or parallel event that appears after and as result of autism and is not the primary cause of the disorder. A hypothesis raised by the authors is that these antibodies are the result of previous neurodevelopmental damage, which we know tend to occur in autism, and so do not participate directly in the disorder. The identification of the protein to which most of these autoreactive antibodies seem to react will help to confirm (or not) this hypothesis, further elucidating the mechanism behind autism and this is Silva, Correia, Vicente and colleagues’ next project.
1 Journal of Neuroimmunology (2004); Vol. 152, pp. 176-182
“Autoantibody repertoires to brain tissue in autism nuclear families”
Original paper’s authors
In collaboration with the Observatório da Ciência e do Ensino Superior (OCES)
Financed by the Fundação para a Ciência e Tecnologia (FCT)