Immune Dysfunction in Autism: A Pathway to Treatment

Abstract

Summary: Autism is a complex and clinically heterogeneous disorder with a spectrum of symptoms. Clinicians, schools, and service agencies worldwide have reported a dramatic increase in the number of children identified with autism. Despite expanding research, the etiology and underlying biological processes of autism remain poorly understood, and the relative contribution from genetic, epigenetic, and environmental factors remains unclear. Although autism affects primarily brain function (especially affect, social functioning, and cognition), it is unknown to what extent other organs and systems are disrupted. Published findings have identified widespread changes in the immune systems of children with autism, at both systemic and cellular levels. Brain specimens from autism subjects exhibit signs of active, ongoing inflammation, as well as alterations in gene pathways associated with immune signaling and immune function. Moreover, many genetic studies have indicated a link between autism and genes that are relevant to both the nervous system and the immune system. Alterations in these pathways can affect function in both systems. Together, these reports suggest that autism may in fact be a systemic disorder with connections to abnormal immune responses. Such immune system dysfunction may represent novel targets for treatment. A better understanding of the involvement of the immune response in autism, and of how early brain development is altered, may have important therapeutic implications.

In Search of Autism Biomarkers: Possible Autism Bio-Markers Discovery at Autism Research and Treatment Center, King Saud University, KSA

“…Whereas evidence suggests that there may be altered immune system function in some children with ASD, the specific alterations appear to vary across studies and will require further analysis to reach consensus [43]. Autism biomarkers were identified that could be categorized according to the key theories that exist regarding the etiology of autism: gastrointestinal factors, immune dysregulation, heavy metal toxicity, neurotransmitter abnormalities, and oxidative stress.…”

Immune System and Neurotrophic Factors in Autism

“…It is indicated that there is a decline occur on anti -inflammatory cytokine levels such as IL -10 and transforming growth factor beta (TGF-β) on autistic individuals. However, in all studies made in this field no consistent results in terms of cytokine patterns could be provided (Careaga et al 2010). Studies in which an increase on autoantibody unique to the brain is indicated support the autoimmune mechanism.…”

“…In autism, there is an increase in the proinflammatory chemokines and modulator cytokines (Cohly and Panja 2005). Detected increase in the level of proinflammatory cytokines such as IL -6, TNF -alpha and monocyte chemoatractan protein 1 (MCP -1) in the brain samples and cerebrospinal fluid indicates that active neural inflammatory process is continuing in autism (Careaga et al 2010). TNF-alpha is a strong immunomodulatory cytokine that is produced by macrophages and partly by active T cells.…”

“…This region includes a vast of genes. One of these genes is the complement protein C4 gene which is important for natural immunity (Careaga et al 2010). The relation of complement 4B null allele with autism related to various autoimmune diseases was examined by Mostafa and Shehab (2010).…”

“…It is indicated that in Egyptian children C4B null allele frequency is significantly higher. The relation of other gens such as macrophage migration inhibitor factor (MIF) gen and serine and threonine kinase C gen, PRKCB with autism is indicated (Careaga et al 2010).…”