Hasil penelitian dari UC Davis M.I.N.D. Institute and Center for Children's Environmental Health telah menemukan bahwa terdapat keterkaitan antara sistem kekebalan tubuh pada darah seorang ibu dan sel otak anaknya yang menderita autis, yang memiliki kemungkinan untuk mempengaruhi perkembangan otak si bayi. Penemuan ini meningkatkan kemungkinan pemberian kekebalan tubuh dari seorang ibu ketika mengandung merupakan salah satu faktor resiko penyakit autis dan pada saat yang sama, penanganan yang baik sebelum melahirkan dapat mencegah penyakit tersebut pada beberapa anak menurut Judy Van de Water professor rheumatology, allergy dan clinical immunology.
Judy dan timnya memulai penelitian terhadap sampel darah dari 123 orang ibu yang 61 orang diantaranya memiliki anak yang menderita autis. Mereka mengisolasi antibodi IgG dari sampel kemudian memberikan antibodinya kepada jaringan otak bayi menggunakan analisa western blot yang mendeteksi reaktifitas antibodi terhadap protein. Hasilnya mengungkapkan pola reaktifitas yang spesifik terhadap 2 protein pada 7 otak bayi dari 61 contoh dari anak penderita autis.
Judy dan timnya belum terlalu mengerti mengapa IgG merespon protein dari otak bayi dengan sangat baik, namun perkiraan mereka bahwa kemunculan ini diperoleh dari antibodi sang ibu ketika mengandung yang diberikan kepada si bayi dan juga pengaruh dari lingkungan semakin menguatkan munculnya autis.
Karakteristik dari autis - penurunan mental, keterbatasan bahasa, prilaku berulang - biasanya terlihat sangat jelas diawal kehidupan sang anak. Beberapa anak lainnya mulai menderita autis ketika usia 12-24 bulan.
Antibodi IgG bertanggungjawab terhadap sistem kekebalan tubuh untuk jangka panjang dalam merespon infeksi, namun dapat juga berkontribusi terhadap penyakit autoimmune seperti arthritis, multiple sclerosis dan lupus. IgG juga menembus plasenta untuk memberikan sistem kekebalan tubuh kepada fetus dan bayi yang baru lahir. Inilah yang menjadi salah satu alasa Judy meneliti peran IgG sebagai faktor potensial penyebab autis.
Untuk selanjutnya, Judy ingin mengetahui efek dari IgG terhadap wanita ketika mereka mengandung, apakah akan menghasilkan respons yang sama seperti respons terhadap protein pada otak bayi.
Sumber : Science Daily, 12 Februari 2008
Thursday, February 14, 2008
Autis dan Sistem Kekebalan Tubuh Ibu.
Monday, February 11, 2008
Brain Signal Linked to Autism
By imaging the brains of adolescents with a high-functioning form of autism as they played a social-interaction game, scientists have identified a physiological deficit specific to the disorder. The researchers believe that the change is linked to a diminished sense of self. The findings, recently published in the journal Neuron, could help guide future research into the nature of autism and potentially lead to new ways to diagnose and treat the disorder.
"I think this is an exciting advance," says Uta Frith, a professor at University College London, in England, who wrote a preview of the paper for Neuron. Most studies find only subtle differences in people with high-functioning autism, "so it's quite impressive to find such a big difference," she says.
Autism is a complicated and heterogeneous developmental disorder marked by problems in language and social behavior. No medical tests exist to detect the disorder, so children are typically diagnosed based on doctors' observations. Scientists are avidly searching for more objective markers of autism, but identifying specific brain abnormalities has been a challenge.
Researchers at Baylor College of Medicine, in Houston, believe that they have now identified a specific physiological marker of the disorder. Read Montague, Pearl Chiu, and their colleagues scanned the brains of adolescents with Asperger's syndrome, a high-functioning form of autism, while they played an interactive trust game.
In the game, one person, designated the investor, chooses an amount of money to send to a second player, the trustee. The money is tripled en route, and the trustee must then decide how much to give back to the investor. When played by normal volunteers, the game unfolds in a very characteristic fashion: generous gestures are met with generous responses, while selfish ones inspire selfishness in return.
Brain activity also follows a stereotyped pattern. A study by Montague and his colleagues. published in 2006, imaged the brains of both the investor and the trustee as they played the game. The researchers discovered a specific signal in the cingulate cortex, part of the brain that integrates information from both the cortex and the body, that was detected only when the investor thought about how much money to give the trustee. A second signal was seen only when the investor received his or her return from the trustee. "We see a 'self, other, self, other' pattern," says Montague, director of the Human Neuroimaging Lab at Baylor. "We think that's an unconscious assessment of who the actions should be attributed to."
According to the new findings, people with Asperger's play the game just as a nonautistic person would, but they lack the characteristic "self" signal in the brain. Normal people lack the signal only when they think that they are playing against a computer, suggesting that autistic people view interactions with other people similarly to the way that normal people think about interacting with a computer. "This approach allows a somewhat objective look at something hopelessly subjective--sense of self," says John Gabrieli, a neuroscientist at MIT.
While the findings are clearly intriguing, it's not yet clear what they mean. One popular theory of autism is that people with the disorder lack a normal theory of mind--the ability to imagine the thoughts and actions of others. Identifying a specific deficit linked to thoughts of self could help narrow down what has gone wrong in that process. "People think autism is linked to a lack of understanding of what a partner is doing," says Chiu. "But maybe they don't understand their own role in the social exchange."
Other scientists interpret the results further, suggesting that this signal is linked to a sort of internal reputation assessment in the brain. "If you are a normal person, when you invest money in the game, you are thinking about how you will look in the eyes of your partner," says Frith. "That's precisely what the theory of mind hypothesis would project is wrong with people with autism."
Other autism experts are unwilling to make such a leap. "I'm skeptical about how much [the Baylor College study] tells us about which capacities are intact and engaged in autism," says Matthew Belmonte, a scientist at Cornell University, in Ithaca, NY. "I'm not convinced they have a deficit at all. Maybe they have adopted a different cognitive strategy."
Regardless of the deeper meaning of their findings, Montague and his team ultimately hope to develop the brain-imaging results into a diagnostic test. They have converted the activity signal from the cingulate cortex into a simple numerical score, which correlates well with a clinical test for the severity of autism. Eventually, they hope to be able to show, for example, "that if you get a 3 rather than a 14, you are 80 percent more likely to be a high-functioning autistic," says Montague. Such a tool could potentially also be used to test the effectiveness of new behavioral treatments, he says.
However, much work remains to be done before such a test could be used in a doctor's office. "We need to make it simpler and test people with a wider range of IQs," says Montague. The Asperger's volunteers in the current study had an above-average IQ.
from here
Friday, January 18, 2008
DNA Deletion Linked to Autism
"This is one of the single largest [influences] and most frequent genetic causes for autism identified so far," says Bai-Lin Wu,director of the Genetics Diagnostic Laboratory at Children's Hospital Boston and one of the senior authors on the study.
Autism spectrum disorder--or autism, as it is commonly called--refers to a group of developmental disabilities with wide-ranging language, social, and behavioral symptoms. The disorder is known to have a strong genetic influence, with up to 90 percent of cases thought to have a genetic component. However, because the disorder is linked to a combination of genetic variations, each playing a minor role, identifying specific genetic triggers has been difficult. Now new microarray technologies, which allow scientists to screen a million or more genetic variations in thousands of patients, are enabling the much larger studies needed to pinpoint these triggers.
In the new paper, scientists say that they used microarrays to scour the DNA of more than 2,000 individuals with autism. They found that deletion or duplication of approximately 500 of the same DNA letters on chromosome 16 was strongly linked to autism, accounting for about one percent of cases. "While that doesn't sound like a huge number, the fact that these people carry the identical spontaneous deletion or duplication would be incredibly unlikely to happen by chance," says Mark Daly, a geneticist at Massachusetts General Hospital's (MGH) Center for Human Genetic Research, in Boston, and at the Whitehead Institute, in Cambridge, and one of the study's senior authors.
The results were independently identified by three different groups--at MGH; Children's Hospital Boston; and deCODE Genetics, in Iceland--that are studying three different populations, giving added weight to the work.
The findings build on previous reports that autism is linked to genetic deletions or duplications that arise spontaneously, rather than being passed down through generations. In almost all cases, parents of the affected people did not carry the chromosome 16 variation.
One of the most immediate clinical benefits of the research will be the development of inexpensive diagnostic tests. "Because the variation occurs so frequently, you could directly test for the presence or absence of a duplication or deletion as part of standardized genetic testing for autism," says James Gusella, a neurogeneticist at Harvard Medical School, in Boston, who participated in the research. For example, children who show developmental delays but are too young to undergo clinical autism testing could be screened for this variation, allowing parents and doctors to prescribe intervention for those who test positive. "We will be able to find at-risk children early on so that language and behavior problems can be treated much earlier," says Yiping Shen, director of research and development at Children's Hospital's Genetics Diagnostic Laboratory, who was also involved in the work.
Such testing could also predict if parents with one autistic child are at greater risk of having another; if their child's autism is linked to a spontaneous variation, they are at no greater risk than the general population. Researchers at Children's Hospital, which provides genetic testing to families, are already developing a clinical diagnostic test.
Scientists are also trying to pinpoint the specific gene or genes within this section of DNA that underlie the increased risk. Daly and his collaborators plan to sequence this region of the genome in another group of people with autism, in search of single-letter mutations that might disrupt the function of specific genes. "Genetics provides us with the only opportunity to gain insight into the biological mechanisms that underlie autism," says Daly. "We can look at individual gene discovery as a small first step in the overall path to develop treatments."
Previous studies have identified autism risk genes. However, these studies have focused on people with genetic disorders that often co-occur with autism, such as Fragile-X syndrome, complicating the role those genes play in the disorder. "Up until now, we haven't had the capacity to look at a single gene that is associated with pure autism," says Gusella.
The findings could point to additional spots in the human genome to search for autism risk genes. The variation on chromosome 16 lies within a genetic "hot spot," an area that is predisposed to undergoing structural duplications due to the architecture of the DNA, says Evan Eichler, a geneticist at the University of Washington in Seattle, who wrote an editorial accompanying the paper. "Every time we produce gametes, there's a finite probability of this region to duplicate," he says. In addition, the region has a high concentration of genes that are rapidly evolving in humans. While the significance of that finding is not yet clear, it may explain autism's status as a relatively young disease.
