Researchers have developed a blood test for autism spectrum disorders (ASDs) that outperforms existing genetic tests while presenting evidence that abnormal immunologic activity affecting brain development may help explain some of autism’s origins. The findings also suggest a new direction for genetic research on autism and the search for treatments.
The blood test, described December 5 in the online open-access journal PLOS ONE and based on the largest gene-chip investigation ever done in autism, could enable early diagnosis of autism in about two-thirds of patients before clear symptoms start to appear (the average age of diagnosis in the U.S. is 5 years).
Researchers led by Sek Won Kong, HMS instructor of pediatrics at Boston Children’s Hospital, and also a member of the hospital’s Informatics Program (CHIP), analyzed blood samples from 66 male patients with ASDs (from Boston Children’s and several other hospitals in collaboration with the Autism Consortium of Boston) and compared them with 33 age-matched boys without ASDs. Using microarrays, they looked for RNA signatures reflecting differences in gene activity, or expression, between the two groups.
“Since brain biopsy isn’t a viable option for research, we asked whether blood could serve as a proxy for gene expression in the brain,” said Isaac Kohane, HMS professor of pediatrics at Boston Children’s and director of CHIP. “We found that it could, though we and others were initially skeptical.”…
Analyzing the blood samples, Kong and colleagues flagged 489 genes as having distinct expression patterns in the ASD group, then narrowed this to a group of 55 genes that correctly identified or ruled out autism in 76 percent of samples. They validated their findings in a second group of 104 male and female patients with ASDs and 82 controls, achieving an overall classification accuracy of 68 percent (73 percent for males and 64 percent for females)…
“It’s clear that no single mutation or even a single pathway is responsible for all cases,” said Kohane, who is also senior investigator on both studies. “By looking at this 55-gene signature, which can capture disruptions in multiple pathways at once, we can say with about 70 percent accuracy that ‘this child does not have autism,’ or ‘this child could be at risk,’ putting him at the head of the queue for early intervention and evaluation. And we can do it relatively inexpensively and quickly.”…
The 55 genes whose expression was altered also suggest more than one path to what we know as autism. Based on their genetic signatures, subjects with ASDs clustered into four subgroups marked by changes in different biological pathways:
• Synaptic pathways, specifically long-term potentiation pathways (essential for memory and learning), and neurotrophic pathways (signaling neurons to survive, develop and grow)
• Immune/inflammatory pathways
“In our sample, about half of the autism cases had some sort of alteration on immune pathways, synaptic pathways or both,” said Kong.