Tuesday Thoughts: Immune Function in Autism and (of course) Heterogeneity

Example of an antibody

Last week, Dr. Judy Van de Water of UC-Davis gave a talk about current research on immune system dysregulation in autism at the Thompson Center here at MU.  This talk came at an opportune time, as many debates have spurred from some recently published reviews on this topic.   Dr. Van de Water presented some exciting findings, but, refreshingly, remained hesitant to overgeneralize their implications.

Throughout her talk, Dr. Van de Water illustrated potential relationships between the immune system and the development of autism.  For instance, out of the hundreds of gene variants thought to be associated with autism, many are related to immune function.  Also, studies have found alterations in the expression of these genes, as well as abnormal activation of immune-related brain cells and altered brain and cerebrospinal fluid levels of cytokines (immune-related signaling molecules), in autism.

Dr. Van de Water emphasized, though, that the data behind these findings represent the mean (or average) of individuals with autism, not the majority.  These findings do not reflect the inherent heterogeneity (or variability) of immune function in autism.  Dr. Van de Water expressed that while some individuals with autism may have a hyperactive immune system, others may have immune system deficits, and still others may have completely normal immune function.

Additionally, Dr. Van de Water presented findings related to antibody production and autism.  Antibodies function as the body’s defense system against foreign substances and are upregulated in states of immune system activation.  Some antibodies, called autoantibodies, may fight against the body’s own cells.  In autism it seems there are higher levels of autoantibodies in certain brain regions, such as the cerebellum.  This heightened antibody response in the cerebellum may be related to decreased cognitive abilities.

Lastly, antibodies may be related to the development of autism in utero, as some maternal antibodies can cross the placenta and affect fetal brain development.  Some mothers of children with autism express a specific pattern of these antibodies.  Interestingly, a polymorphism of the immune-related MET gene may lead to these altered patterns of antibody expression, meaning this MET variant may function as a susceptibility gene for autism.

At the end of her talk, Dr. Van de Water described a blog post she was asked to write for the Simons Foundation Autism Research Initiative website in light of the thought-provoking column on autism and immune function published in the New York Times. In her post she emphasizes the heterogeneity of autism, and that “generalizing the findings [related to immune dysregulation] from one subtype or group to another can be dangerous where treatment is concerned.”  As has been demonstrated before, the questions related to the study of autism greatly outnumber the answers.  Instead of overgeneralizing the answers, we need to keep asking the questions.

Tuesday Thoughts: Pieces of the Puzzle

The world of autism research has been hopping lately with several new studies claiming to explain potential causes of autism and the apparent increasing incidence of this disorder.  The media, including major publications, has jumped on board with the excitement about these findings.

One study outlines the potential of increased age in fathers to heighten the risk of autism in their children.  The authors of this study explain that older dads pass on more small DNA mutations to their children than do younger dads, a difference which may explain some cases of autism.  Considering that, in the population studied, the average paternal age has increased over time, it’s easy to see how the authors also conclude that increased paternal age may contribute to the increasing incidence of autism.

Other studies recently published, and then reviewed in The New York Times, implicate heightened maternal immune response in the development of autism in the womb.  Infections such as the flu seem to bring about an exaggerated immune response in some pregnant women, leading to disruptions in the development of their children.  Many studies have demonstrated a relationship between this prenatal immune system dysregulation and autism.

What’s missing in the media’s interpretations of these studies?  In the midst of flashy results, the fact that autism is still largely unexplained gets pushed out of the picture.  Although there seem to be breakthroughs on the horizon, the studies outlined above may only account for a fraction of the cases of autism. These findings and their implications are just pieces of the puzzle.

Science writer Virginia Hughes stated in a recent piece,  “how many times do researchers have to say, ‘The cause of autism is really complicated’ before journalists and the public accept that the disorder can’t be explained by a gene, a brain scan, a father’s age, a gluten-rich diet or risk factor du jour?”

I share Hughes’s sentiments.  We are dealing with what seems like a mega-10,000 piece puzzle, and we’ve yet to find all the pieces.  When we’ve gathered as may as we can, then, and only then, will we be able to put them together and start to explain.