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Immune Changes Linked to Regression, GI Distress & Repetitive Behaviors

Researchers have found new evidence associating autistic regression with a pattern of immune dysfunction, brain changes, severe repetitive behaviors and GI distress.

Past research has linked abnormal immune responses to autism – particularly regressive forms. The new report shows elevated levels of key immune cells – called dendritic cells – in children with autism. The study links this immune abnormality to enlargement of the amygdala, a part of the brain that controls emotional responses.

The report appears online in the journal Brain, Behavior and Immunity. It represents findings from an Autism Speaks Suzanne and Bob Wright Trailblazer Award for research into GI disorders associated with autism. The lead investigator is Paul Ashwood, Ph.D., of the M.I.N.D. Institute, at the University of California, Davis.

“These results further support a link between immune function, autism and medical problems such as GI dysfunction,” Dr. Ashwood says. “Dendritic cells are the ‘generals’ of the immune system. They are key players in directing many immune responses.” Dendritic cells play a particularly powerful role in the immune response to microorganisms. These include disease-causing germs as well as normal digestive bacteria.

“This study provides important clues to understanding autistic regression by pinpointing dysfunction of the immune system,” adds Autism Speaks Chief Science Officer Geri Dawson, Ph.D. “Further, it links this abnormality to changes in a brain region that controls emotional responses.”

Some children with autism appear to develop normally in the first year or two of life. They then regress, losing developmental skills, particularly in sociability and communication. Studies have linked this autism pattern with greater frequency of medical problems such as GI distress.

“The next critical step,” Dr. Dawson says, “is to consider the implications of Dr. Ashwood’s findings for treating children with autistic regression. Additional studies by Paul and his team are already exploring this question.”

Participants in the study included 57 toddlers, ages 2 to 3, with ASD. Of these, 26 had autism symptoms from the first year of life. Another 31 were described by parents as having typical early development followed by regression in the second year. For comparison, the study also included 29 typically developing toddlers. Researchers took blood samples, assessed behavior and health, and conducted brain imaging studies using magnetic resonance imaging (MRI).

They found that children with ASD had significantly more dendritic cells than did typically developing toddlers. Higher levels of one type of dendritic cell (plastmacytoid) related to developmental regression. That is, to later onset of autistic behaviors. This later-onset pattern also related to enlargement of the amygdala. Previous studies have likewise linked enlargement of this brain structure with autism. In particular, it has been associated with increased social disability and anxiety.

Dr. Ashwood’s team found that children with more dendritic cells had more severe repetitive behaviors. They were also more likely to suffer chronic constipation. In the digestive tract, dendritic cells engulf many kinds of bacteria – both dangerous germs and normal digestive organisms. They carry these bacteria to lymph nodes to trigger various types of immune responses.

“We know that the relationship between gut bacteria and host immune responses are very important.” Dr. Ashwood says. “If these immune cells react inappropriately to gut bacteria, this could lead to inflammation. Changes in dendritic cell function could impact and disrupt many immune processes including T cell activation and autoantibody production that have been shown to be dysfunctional in autism,” he adds. Previous studies have associated some autism-linked genes with both dendritic cell function and GI disorders.

Dr. Ashwood’s Autism Speaks Trailblazer research grant will allow his team to continue following the children in the study. They will evaluate a probiotic therapy for restoring normal GI function. In addition, they will use animal models to better understand how immune changes relate to autism’s behavioral and physical symptoms. Dr. Ashwood’s collaborators in this research include Alessio Fasano, M.D., at University of Maryland School of Medicine, and Sarkis Mazmanian, Ph.D., and Paul Patterson, Ph.D., of the California Institute of Technology.

Autism Speaks is currently funding a number of immunology studies concerning autism. You can explore these and other funded research using this website’s Grant Search.