Etiology in Autism
Harumi Jyonouchi; Sining Sun; Hoa Le
University of Minnesota, Minneapolis, MN
Etiology of autism is unknown. However, there appears to be a casual association between onset of regression/autistic behavior and infant immunization/viral infection/adverse reactions to common food antigens (gluten and cowÃs milk). Previous literature indicates the presence of autoantibodies against neuronal cells in autistic children and subtle immune abnormalities such as skewed T2 responses.
In this study, we hypothesized that children with regression autism may have aberrant immune responses against these common, usually benign environmental factors, resulting in inflammatory and/or autoimmune conditions in the CNS. As a first step to examine our hypothesis, we determined innate and adaptive immune responses in children with autism
spectrum disorders (N=35, Age 2-14 yrs, median: 6 yr, 24 males and 9 females).
Innate immune responses are assessed by measuring production of TNF-,IL-1, IL-6, sTNFRI, and sTNFRII after incubating peripheral blood mononuclear (PBMN) cells overnight with endotoxin (LPS: 0.1 to 10 Âµg/ml). Adaptive immune responses are assessed by measuring T cell cytokine (IFN-,IL-4, IL-5 and IL-10) production in response to recall antigens (tetanus and
dust mite), mitogens (PHA and Con A) and IFN- inducing cytokines (IL-12p70 and IL-18) after culturing cells for 4 days with these stimuli. Production of IL-12p40, IL-18, and TGF- was also measured in this setting.
Controls were obtained from healthy normal children (N=17, Age 2-16 yrs, median: 11 yrs). Onset of autism/developmental regression with immunization was reported in 27/35 patients and 32/35 patients were reported
to have improvement of behavior by parents/teachers/therapists with a casein-free/gluten-free diet. Autistic children produced higher TNF- (p<0.01), sTNFRII (p=0.038), and IL-6 (p=0.01) with a low dose of LPS (0.1 Âµg/ml) than controls.
This is due to the presence of a subset of patients who produced large amounts of these cytokines. In fact, 27/35 (77.1%) study subjects produced higher than the maximum levels of TNF-, sTNFRII, IL-6 and/or IL-1 observed in controls with a low dose of LPS. We also observed elevated serum levels of these cytokines in 8/18 autistic children.
Our results thus indicate a high frequency of excessive innate immune responses in children with regression autism. These results may partly explain apparent association between onset of regression/autistic behavior
and immunization in these children. Production of IFN-, IL-5, IL-10 and IL-12p40 was highly variable in autistic children. IL-4, IL-18, and TGF- production by PBMN cells were generally low and did not differ between the study subjects and controls.
We also assessed T1/T2 responses by comparing the ratio of IFN-/IL-5 levels produced with recall antigens. The ratio of IFN-/IL-5 did not differ between autistic children and controls. However, 7 and 8 out of 35 autistic children produced significantly high IL-12p40 with recall antigens and IL-12/IL-18, respectively. IL-10 production was markedly variable in autistic children: 10 and 11 out of 35 subjects produced high amounts of IL-10 with PHA and tetanus, respectively, while 12/35 subjects produced significantly low IL-10 with PHA as compared to controls.
These results also indicate aberrant production of regulatory cytokines for T cell responses in subsets of autistic children.
Study Lends Support to Leaky Gut Theory of Autism
article from FEAT!
This is consistent with increasing evidence for gut
epithelial dysfunction in autism – Dr. Simon Murch