International Meeting for Autism Research: Biomarkers of Immunological and Metabolic Comorbidities in Autism Spectrum Disorders

Biomarkers of Immunological and Metabolic Comorbidities in Autism Spectrum Disorders

Friday, May 21, 2010
Franklin Hall B Level 4 (Philadelphia Marriott Downtown)
3:00 PM
J. Bradstreet , Pediatrics, International Child Development Resource Center, Melbourne, FL
R. F. Palmer , Department of Family and Community Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX
Background: Recent published observations have found a consistent pattern of oxidative stress and immunological activation in children with autism spectrum disorders (ASD).  Since there is broad consensus in the medical literature that the brain is highly sensitive to oxidative stress and immunological signals, the presence of excessive free radicals and peripheral immune activation would be expected to have potential clinical implications for affected individuals.

Objectives: For several years our population of ASD patients has been evaluated using urinary biomarkers of oxidative stress and immune activation. These include: isoprostane, 8-oxoguanosine (8OHG), 8-hydroxydeoxyguanosine (8OHdG), and neopterin.  Urinary porphyrins, isoprostane and neopterin have been previously documented to be significantly elevated in the ASD population relative to controls.  The RNA oxidation marker, 8-oxoguanosine has not been published in the autism population, but has been observed clinically to be significantly elevated relative to laboratory norms and appears to correlate with symptom severity within ASD. It is a potential marker of mitochondrial dysfunction. We compared our historical database to a population of neurotypical children.

Methods: A retrospective database review was undertaken to find children with ASD diagnoses for which no prior immunological or antioxidant therapy had been undertaken. Patients were selected from populations in the US, France and Norway which could provide a broad international assessment of the biomarker pattern in the ASD group. After extensive chart review to exclude prior treatment and children without unequivocal ASD, (N=212 ASD children, ages 1 to 8) were selected. These were internally compared within the group for subset evaluations and cross-correlations between the biomarkers as well as to the control population of healthy neurotypical children (N=43) gathered from volunteers in the US and France. Outliers greater than 3SD were excluded from the analysis, resulting in a final study group (N=197).  For all specimens, a first morning urinary sample was collected and processed using standard laboratory methods of HPLC and triple quadrupole dual mass spectroscopy.

Results: For all the major variables: 8OHG, 8OHdG, neopterin, uroporphyrin and coproporphyrin, the observed means were significantly higher for the ASD population (p<0.001). These data are consistent with previous observations published regarding urinary neopterin, isoprostane and porphyrins.  The observed increase in RNA oxidation (8OHG) is a new observation within  ASD.  Unlike prior reports we did observe significantly higher DNA oxidation in this group. The observed differences were highest for the population under age 5 for isoprostane (p <0.05), coproporphyrin (p < 0.001), and neopterin (p < 0.001). In addition, strong correlations existed between markers of oxidation and neopterin as well as coproporphyrin.

Conclusions: This large retrospective controlled evaluation replicates previously published observations of abnormally increased neopterin, isoprostane and coproporphyrin in the ASD population and extends these observations to oxidation of RNA and DNA.  It further demonstrates significant correlations of these biomarkers which may have value in biological subtyping as well as in the selection of interventions for these subgroups. The observed oxidation of RNA needs to be further correlated with mitochondrial assessments, and the oxidation of DNA is of obvious concern.

See more of: Comorbidities
See more of: Clinical & Genetic Studies