Study: Immune System Disruption Implicated in Autism

There have been a couple of good studies published in recent weeks that look at the possible connection between disruptions of the immune system and autism.  But one in particular that was published just last week in PLoS One looks to be the best of the bunch.

I have not read it in depth yet so I might be getting some of the details wrong.  But in general, it looks like these researchers managed to take the many rare genetic mutations that have been seen in autism and demonstrate that many of these mutations converge on biological paths that control immune system signaling.  The researchers suggest that these disruptions have the potential to alter typical brain development and lead to the symptoms of autism.

I would normally include the abstract of the study but I think these paragraphs from the conclusion puts the findings into prospective -

Interestingly, there is also mounting evidence at the cellular and tissue levels that more in depth investigation of an immune component is warranted in ASD. For instance, multiple studies have demonstrated altered cytokine profiles in ASD patients, and altered TGF-B concentration in serum and CSF correlates with disease severity. Others have described various autoimmune phenomena including autoantibodies to neural antigens and maternal-fetal cross-reactive neural antibodies. There is also indication of altered innate cellular immunity in ASD, such as differences in gene expression and altered response to immunostimlulatory ligands in both natural killer and monocytic cells from ASD patients. Post-mortem brain tissue from ASD patients shows increased microglial density in grey matter, an activated morphology, and secretion of a cytokine profile consistent with a pro-inflammatory state, most prominent in the cerebellum. Moreover, microglia from MeCP2- null mice—a model of the Autism Spectrum Disorder Rett Syndrome—produce a conditioned media that damages synaptic connectivity via a glutamate-excitotoxicity mechanism. While all of this work provides post-hoc evidence for altered immune response in ASD, our results suggest a direct link between implicated genes in ASD and molecular pathways involved in immune signaling.

This considerable attention to the immune response in previous ASD research has resulted in two prevailing theories: one suggests exogenous factor(s) stimulate neuro-inflammation during development, while the other postulates autoimmune activation causes ASD pathology. However, it is equally possible—as our results support—that the mutations described in ASD result in aberrant signaling regulation of immune cells during neurodevelopment. This could result in cell-autonomous activation and/or improper response to otherwise nominal stimuli, such as occurs in the autoinflammatory syndromes. Alternatively, as glia are increasingly implicated in normal formation of synaptic connectivity —and we have demonstrated a significant proportion of ASD-implicated genes appear to be glial-specific—it is possible that genomic aberrations ultimately funnel through core signaling pathways of glial cells to disrupt formation of neural networks independent of an inflammatory mechanism. In support of this notion, a number of recent reports have demonstrated that these same cytokine signaling pathways are central to proper brain development. Furthermore, signaling through the NFkB pathway has been shown to be important in synaptic plasticity independent of an inflammatory mechanism.

The study is open access so go read it if you are interested in the subject.

References

Ziats MN, Rennert OM. Expression Profiling of Autism Candidate Genes during Human Brain Development Implicates Central Immune Signaling Pathways. PLoS One. 2011;6(9):e24691. Epub 2011 Sep 15.
PubMed PMID: 21935439. DOI: 10.1371/journal.pone.0024691