Immunity and inflammation play a very important role in many diseases, including autism.
Immune dysfunction in autism:
“Autism is a complex and clinically heterogeneous disorder with a spectrum of symptoms. Published findings have identified widespread changes in the immune systems of children with autism, at both systemic and cellular levels. 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.” (Careaga et al. Neurotherapeutics 2010) There are many reports of cytokine imbalances in autism spectrum disorders (ASD). These imbalances could have a pathogenic role, or they may be markers of underlying genetic and environmental influences. Cytokines act primarily as mediators of immunological activity but they also have significant interactions with the nervous system. Cytokine profiles change dramatically in the face of infection, disease, and toxic exposures. Ashwood et al. (Brain Behav Immun. 2011) reported on significant increases in plasma levels of a number of cytokines, including IL-1β, IL-6, IL-8 and IL-12p40 in the ASD group compared with controls. Suzuki et al. (PLoS One 2011) reported that the plasma concentrations of IL-1β, IL-1RA, IL-5, IL-8, IL-12(p70), IL-13, IL-17 and GRO-α were significantly higher in subjects with ASD compared with the corresponding values of matched controls. Okada et al. (Prog Neuropsychopharmacol Biol Psychiatry 2007) and Ashwood et al. (J Neuroimmunol. 2008 ) reported on decreased serum levels of transforming growth factor- beta1 (TGFb1) in patients with autism, with lower TGFb1 levels associated with lower adaptive behaviors and worse behavioral symptoms, suggesting that immune responses in autism may be inappropriately regulated due to reductions in TGFb1.
Elevated serum levels of interleukin-17 (IL-17) in children with autism
CD4-positive T lymphocytes play a major role in the regulation of adaptive immunity. Upon activation by antigen-presenting cells (APC), naive antigen-specific CD4+ T cells differentiate into different subsets of T cells. In addition to the classic T-helper (Th)1 and Th2 cells, several novel effector T cell subsets have been recently identified, including Th17 cells. Th17 CD4 T cells are characterized by production of the cytokines interleukin (IL)-17A (IL-17) and IL-17F, and IL-21 and IL-22. Since their discovery in 2003, there have been numerous studies on Th17 cells, and they have emerged as key players in the pathogenesis of some autoimmune neuroinflammatory diseases and other autoimmune disorders traditionally attributed to Th1 cells. Children with autism had significantly higher serum.
Live Borrelia activates IL1-Beta gene expression
Activation of Human Monocytes by Live Borrelia
Mast cell activation and autism
Despite the impressive rise in the prevalence of autism during the last two decades, there are few if any clues for its pathogenesis, early detection or treatment. Increasing evidence indicates high brain expression of pro-inflammatory cytokines and the presence of circulating antibodies against brain proteins. A number of papers, mostly based on parental reporting on their children’s health problems, suggest that ASD children may present with “allergic-like” problems in the absence of elevated serum IgE and chronic urticaria. These findings suggest non-allergic mast cell activation.