Immunological Factors, Genes, and the Environment
A half-day symposium providing insight into research and current trials that point to the potential benefit of medical treatments to address environmentally-triggered impairments associated with autism spectrum disorders.
Recorded June 1, 2013 at UC Davis MIND Institute Auditorium in Sacramento, California. Videos are courtesy of Autism Research Institute, UC Davis MIND Institute & Autism Speaks.
Handouts are online at: http://www.ariconference.com/enews/mind_6-1.pdf
Is There a Connection Between Immune Function and Autism?
The ideal immune system will:
- Recognize all foreign organisms (bacteria, viruses, parasites, fungi, worms).
- Efficiently and rapidly destroy invaders.
- Prevent a second infection with the same microbe (have a good memory).
- Never cause damage to self.
Things that can go wrong:
- Immune deficiency/dysfunction: defective or ineffective response.
- Hypersensitivity: Over-reaction to innocuous foreign material, out of proportion to potential damage (allergy).
- Autoimmunity: Inappropriate reaction towards self, loss of self-recognition.
- Inflammation: Too-vigorous attack against invaders with “bystander” damage to normal tissue.
Dysregulation of immunity in people with autism can lead to any of these four problems.
There is a tendency towards a positive family history of autoimmunity in families – Rheumatoid Arthritis, Thyroiditis - with an ASD child. Many, many types of autoantibodies [add link on autoantibodies to http://www.pediatricbioscience.com/mar/immunology.html] (against “self” tissues) have been found in ASD children but the significance of the many types of anti-brain antibodies is not yet clear. Several studies find that some ASD children have low immunoglobulins (IgG, IgM, IgA), and/or low T cell numbers, altered cytokine profiles, and/or low-normal functioning and/or low NK cells; a subset of children have true immunodeficiency. Some children have low serum IgA, predisposing them to respiratory and GI infections.
Antibodies are divided up into classes:
- IgA: Mucosal surfaces - if this is low, it predisposes to respiratory and GI infections as well as autoimmunity; it is sometimes low in ASD children
- IgM: Rapid response bloodstream antibody made at the beginning of an infection; can be high or low in ASD
- IgG: Slower but longer lasting bloodstream antibody; can be high or low in ASD
- IgE: Allergy; can be high or normal in ASD
Conclusion #1: A child on the autism spectrum with recurrent infections deserves an immune evaluation for immunodeficiency.
Conclusion #2: A child on the autism spectrum with eczema, chronic nasal symptoms, asthma, significant GI symptoms, or recurrent respiratory infections deserves an allergy evaluation for IgE inhalant and food allergies.
A few of the studies published on immune function and autism:
Onore C, Careaga M, Ashwood P. The role of immune dysfunction in the pathophysiology of autism. Brain Behav Immun. 2011 Aug 28.
Brown AC, Mehl-Madrona L. Autoimmune and gastrointestinal dysfunctions: does a subset of children with autism reveal a broader connection? Expert Rev Gastroenterol Hepatol. 2011 Aug;5(4):465-77
Atladóttir HO, Pedersen MG, Thorsen P, Mortensen PB, Deleuran B, Eaton WW, Parner ET. Association of family history of autoimmune diseases and autism spectrum disorders.
Pediatrics. 2009 Aug;124(2):687-94.
Manzardo AM, Henkhaus R, Dhillon S, Butler MG. Plasma cytokine levels in children with autistic disorder and unrelated siblings. Int J Dev Neurosci. 2011 Dec 16
Braunschweig D, Duncanson P, Boyce R, Hansen R, Ashwood P, Pessah IN, Hertz-Picciotto I, Van de Water J. Behavioral Correlates of Maternal Antibody Status Among Children with Autism. J Autism Dev Disord. 2011 Oct 20.
Mostafa GA, Al-Ayadhi LY. Increased serum levels of anti-ganglioside M1 auto-antibodies in autistic children: relation to the disease severity. J Neuroinflammation. 2011 Apr 25;8:39.
Wills S, Cabanlit M, Bennett J, Ashwood P, Amaral DG, Van de Water J. Detection of
autoantibodies to neural cells of the cerebellum in the plasma of subjects with autism spectrumdisorders. Brain Behav Immun 23:64-74, 2009
Enstrom AM, Lit L, Onore CE, Gregg JP, Hansen RL, Pessah IN, Hertz-Picciotto I, Van de Water JA, Sharp FR, Ashwood P. Altered gene expression and function of peripheral blood natural killer cells in children with autism. Brain Behav Immun 23:124-33, 2009.
Heuer L, Ashwood P, Schauer J, Goines P, Krakowiak P, Hertz-Picciotto I, Hansen R, Croen LA, Pessah IN, Van de Water J. Reduced Levels of Immunoglobulin in children with autism correlates with Behavioral Symptoms. Autism Research 1:275-283, 2008.
Goines P, Haapanen L, Boyce R, Duncanson P, Braunschweig D, Delwiche L, Hansen R, Hertz-Picciotto I, Ashwood P, Van de Water J. Autoantibodies to cerebellum in children with autism associate with behavior. Brain Behav Immun. 2011 Mar;25(3):514-23.