Two New Studies Suggest Immune System Dysfunction Plays Role in Autism

2012-04-18 16:57

Many medical professionals have long speculated that children with autism spectrum disorders (ASDs) are more prone to immune system dysfunction. Two new studies published in recent months have found a biological link between autism and immune system factors that could possibly lead to new treatment options.

Using a mouse model, researchers at the University of South Florida are studying the link between amyloid precursor protein (APP) and aberrations in the immune system. APP is best known for its role in Alzheimer’s disease. It is an integral membrane protein that is concentrated in the synapses of neurons (brain cells) and is used for formation and repair.

However, a specific fragment of APP known as sAPP-α has been found to be elevated in the blood of autistic children. This fragment is thought to play a role in T-cell immune responses. sAPP-α is also implicated as a factor in the excessive early brain growth seen with children with autism.

Research team leader Jun Tan MD PhD says that “There are reports of abnormal T-cell numbers and function in some persons affected with autism (but) no specific cause has been identified.” She also notes that the findings could potentially be used as an autism biomarker and medical diagnostic tests could be developed if the findings hold true in further studies, leading to an earlier diagnosis and more effective treatments.

Cytokines, the immune system’s messengers and regulators, was the focus of research conducted at the University of Kansas Medical Center. Cytokines and the immune system are active in many pathways that are shared by those that affect brain development and neurotransmission.

Researchers analyzed the plasma of 99 children with autism between the ages of 5 and 10 and compared the samples to those of 40 age- and gender-matched unrelated healthy siblings without an ASD. There are many different types of cytokines, but the focus of the study was specifically focused on 29 proteins.

Five of the cytokine levels were found to be disturbed that related to the T-helper cell immune system and three were involved in hematopoiesis or the production of blood cells, possibly affecting antibody production required for normal immune system activity.

Merlin G. Butler, professor of psychiatry at the KU Medical Center, said “Our study further supports a disturbed immune system in children with classic autism that may be related to genetic factors as cytokine proteins are coded by genes distributed among the human chromosomes.”

“The importance of identifying early immunological disturbances that may contribute to autism has implications for identifying risk factors, diagnosis and possibly intervention as cytokines may play a role in the function of the developing brain," he concluded.

References:

  • Bailey AR, Hou H, et al. Aberrant T-lymphocyte development and function in mice overexpressing human soluble amyloid precursor protein-α: implications for autism. The FASEB Journal vol. 26 no. 3 1040-1051 March 2012
  • A.M. Manzardo, R. Henkhaus, S. Dhillon, M.G. Butler.Plasma cytokine levels in children with autistic disorder and unrelated siblings. International Journal of Developmental Neuroscience, 2012; 30 (2): 121 DOI:10.1016/j.ijdevneu.2011.12.003
  • Ray B, Long JM, Sokol DK, Lahiri DK. Increased secreted amyloid precursor protein-α (sAPPα) in severe autism: proposal of a specific, anabolic pathway and putative biomarker. PLoS One. 2011;6(6):e20405. Epub 2011 Jun 22.
  • Ashwood P, Krakowiak P, Hertz-Picciotto I, Hansen R, Pessah I, Van de Water J Elevated plasma cytokines in autism spectrum disorders provide evidence of immune dysfunction and are associated with impaired behavioral outcome. Brain Behav Immun. 2011 Jan;25(1):40-5. Epub 2010 Aug 10.
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