Autism and Immunity: Revisited Study

Castellani, M.L.; Conti, Chiara; Kempuraj, Duraisamy; Salini, Vincenzo; Vecchiet, Jacopo; Tetè, Stefano; Ciampoli, C.; Conti, Francesca; Cerulli, Giuliano Giorgio; Caraffa, Auro; Antinolfi, Pierluigi; Galzio, Renato; Shaik, Y.B.; Theoharides, Theoharis C.; Amicis, D. De; Perrella, Alessandro; Cuccurullo, Chiara; Boscolo, P; Felaco, Mario; Doyle, Robert; Verrocchio, C; Fulcheri, Mario

doi:10.1177/039463200902200103

Cited by 25 publications

(19 citation statements)

References 27 publications

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“…Aberrant immunity has been reported to be associated with autism and autism spectrum disorders (ASDs); however, there have been no studies mechanistically connecting a particular immune activity with the aberrant behaviors of individuals with an ASD [1]–[4]. For example, serum IgE levels have been reported to be normal [5], [6] or elevated [7], [8], and mastocytosis has been reported to be associated with ASD [9]. There does seem to be consistency regarding elevated levels of plasma cytokines and neuroinflammation (elevated levels of cytokines in the brain) being associated with ASD [10]–[14].…”

Section: Introductionmentioning

confidence: 99%

Aberrant Immune Responses in a Mouse with Behavioral Disorders

et al. 2011

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BTBR T+tf/J (BTBR) mice have recently been reported to have behaviors that resemble those of autistic individuals, in that this strain has impairments in social interactions and a restricted repetitive and stereotyped pattern of behaviors. Since immune responses, including autoimmune responses, are known to affect behavior, and individuals with autism have aberrant immune activities, we evaluated the immune system of BTBR mice, and compared their immunity and degree of neuroinflammation with that of C57BL/6 (B6) mice, a highly social control strain, and with F1 offspring. Mice were assessed at postnatal day (pnd) 21 and after behavioral analysis at pnd70. BTBR mice had significantly higher amounts of serum IgG and IgE, of IgG anti-brain antibodies (Abs), and of IgG and IgE deposited in the brain, elevated expression of cytokines, especially IL-33 IL-18, and IL-1β in the brain, and an increased proportion of MHC class II-expressing microglia compared to B6 mice. The F1 mice had intermediate levels of Abs and cytokines as well as social activity. The high Ab levels of BTBR mice are in agreement with their increased numbers of CD40hi/I-Ahi B cells and IgG-secreting B cells. Upon immunization with KLH, the BTBR mice produced 2–3 times more anti-KLH Abs than B6 mice. In contrast to humoral immunity, BTBR mice are significantly more susceptible to listeriosis than B6 or BALB/c mice. The Th2-like immune profile of the BTBR mice and their constitutive neuroinflammation suggests that an autoimmune profile is implicated in their aberrant behaviors, as has been suggested for some humans with autism.

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Section: Introductionmentioning

confidence: 99%

Aberrant Immune Responses in a Mouse with Behavioral Disorders

et al. 2011

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“…Autism, and, more broadly, autism spectrum disorder (ASD), is a condition characterized by impaired cognitive and social skills [1], along with a compromised immune function [2][3][4][5]. It can now no longer be denied that the incidence of ASD is alarmingly on the rise in the U.S. [6].…”

Section: Introductionmentioning

confidence: 99%

Empirical Data Confirm Autism Symptoms Related to Aluminum and Acetaminophen Exposure

Seneff

Davidson²,

Liu

2012

Entropy

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Autism is a condition characterized by impaired cognitive and social skills, associated with compromised immune function. The incidence is alarmingly on the rise, and environmental factors are increasingly suspected to play a role. This paper investigates word frequency patterns in the U.S. CDC Vaccine Adverse Events Reporting System (VAERS) database. Our results provide strong evidence supporting a link between autism and the aluminum in vaccines. A literature review showing toxicity of aluminum in human physiology offers further support. Mentions of autism in VAERS increased steadily at the end of the last century, during a period when mercury was being phased out, while aluminum adjuvant burden was being increased. Using standard log-likelihood ratio techniques, we identify several signs and symptoms that are significantly more prevalent in vaccine reports after 2000, including cellulitis, seizure, depression, fatigue, pain and death, which are also significantly associated with aluminum-containing vaccines. We propose that children with the autism diagnosis are especially vulnerable to toxic metals such as aluminum and mercury due to insufficient serum sulfate and glutathione. A strong correlation between autism and the MMR (Measles, Mumps, Rubella) vaccine is also observed, which may be partially explained via an increased sensitivity to acetaminophen administered to control fever.

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“…A dysfunctional gut-blood-brain barrier (7) could expose local mast cells to environmental and innate substances triggering the release of vasoactive, inflammatory and neurosensitizing mediators (44)(45)7). These could also activate susceptibility genes leading to ASD.…”

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confidence: 99%

Autism Spectrum Disorders and Mastocytosis

Theoharides

2009

Int J Immunopathol Pharmacol

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Autism Spectrum Disorders (ASD) are diagnosed in early childhood and include Autism, Asperger's disorder and Pervasive neurodevelopmental disorder - not otherwise specified (PDD-NOS, or atypical autism). ASD are associated with varying degrees of dysfunctional communication and social skills, repetitive and stereotypic behaviors, as well as attention and learning disabilities. Most ASD patients also have food intolerance and other allergic symptomatology indicative of mast cell activation. The number of ASD cases have increased over the last decade to 1/100, but there is no definite pathogenesis or curative therapy. We report that the apparent prevalence of ASD in patients with mastocytosis, a rare disease occuring in 1/4,000 children and characterized by an increased number of hypersensitive mast cells in many organs, is about 1/10 or 10 times higher than the general population. A child with skin mastocytosis [urticaria pigmentosa, (UP)] and regressive autism is presented to illustrate the point. Allergic, infectious, neuroimmune and environmental triggers may activate mast cells to release vasoactive, inflammatory and neurotoxic molecules. These could disrupt the gut-blood-brain-barriers (BBB), and/or activate susceptibility genes, thus contributing to brain inflammation and ASD.

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Autism and Immunity: Revisited Study

Cited by 25 publications

References 27 publications

Aberrant Immune Responses in a Mouse with Behavioral Disorders

Aberrant Immune Responses in a Mouse with Behavioral Disorders

Empirical Data Confirm Autism Symptoms Related to Aluminum and Acetaminophen Exposure

Autism Spectrum Disorders and Mastocytosis

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