- Autism spectrum disorder
(ASD) is a neurodevelopmental disorder affecting children with impaired social,
cognitive and communication skills, usually diagnosed around the 4th
- Current study suggests that using a panel of
biomarkers such as TSH and IL-8 would permit early diagnosis by the first year
of age with consequent early intervention and better outcome.
a set of serum protein biomarkers is likely to improve
diagnostic accuracy for Autism Spectrum
(ASD) enabling early intervention for an improved outlook,
according to a study from the Peter O'Donnell Jr. Brain Institute at
UT Southwestern Medical Center.
study was published in the Journal of Neuroinflammation
one of the many studies conducted that
aim to improve early diagnosis of ASD by shifting focus to measurement of
rather than relying
on behavioral symptoms for diagnosis.
‘Using a panel of proteins improves the diagnostic accuracy of autism spectrum disorder, than when a single biomarker is used.’
Why Do We Need Serum
Biomarkers For Diagnosis of ASD?
appears to be on the rise with more children being diagnosed with autism than
AIDS, cancer and diabetes combined.
available screening tools and diagnostic modalities are prone to subjective interpretation and are difficult to apply on younger children, resulting in delayed diagnosis
. Studies have shown
that earlier diagnosis and therapeutic interventions are associated with a much
present, the diagnosis is made around
the age of 4, when communication and social disabilities have progressed enough
to be apparent
progress has been made in the delineation of certain biomarkers for ASD, no 'universally acceptable biomarker has emerged thus far
. The matter is made all the more difficult due to the heterogeneity of this condition and the other co-existing abnormalities
associated with autism spectrum disorder.
this scenario, the research team set out
to test a panel of proteins in the serum of boys diagnosed with ASD and
comparing the levels with that occurring in typically developing (TD) boys
The study included only boys as autism spectrum disorder is much more common in
Comparing Serum Samples
Of ASD Vs TD Boys - The Study
Testing TSH And IL-8 On The MSD Platform -- The Findings
- For the study,
30 boys with ASD and 30 typically developing
were chosen between the ages of 2-8 years.
serum of both groups was tested initially on the Myriad Rules-Based Medicine (RBM) testing platform. This testing
delineated 11 proteins, which when measured together, could predict the occurrence of ASD
with a modest degree of accuracy.
the 11, five were identified that showed
the highest degree of accuracy. These included TSH, stem
cell factor, monocyte chemotactic protein 4, ferritin, and
- To validate
the above findings of the RBM platform testing, the team ran 30 samples from the
abovementioned, plus additional samples (to increase sample
size) on another testing platform, the
Meso Scale Discovery (MSD) platform. On the MSD platform, the study team
chose to test only 2 of the 5 proteins with
the highest degree of accuracy namely
TSH and IL-8.
- The MSD platform is considered to be more
sensitive for measuring various test proteins
across a wide range of concentrations.
- In 43 ASD samples tested, serum TSH levels was 30% lower than in
- In 36 ASD samples tested, IL-8 levels were found to be 16% higher in ASD boys compared to TD
- The predictive accuracy for IL-8 alone was 74% and
for TSH alone it was 76%. When TSH and IL-8 were measured together, the predictive
accuracy was 82%, with 89% sensitivity and 75% specificity.
- The cut off scores to predict ASD were TSH levels below 1.8 mIU/l and IL-8 levels
above 10.3 pg/ml.
levels of TSH were associated with more severe defects (higher scores) in the
Autism Diagnostic Observation Schedule (ADOS) subdomain scores of ASD
namely social interaction and repetitive behavior.
levels of IL-8 were not associated with ADOS subdomain
- Both TSH and
IL-8 levels did not show any significant correlation between the various autism
subgroups namely regressive autism, non-verbal autism and ASD displaying
gastrointestinal (GI) issues.
findings of the study suggest that biomarkers would be more reliable in
diagnosing ASD than assessment of behavioral symptoms, which may be subject to
inter-observer variation. Also, the measurement of a
panel of protein biomarkers could further improve the diagnostic accuracy.
a very heterogeneous disorder, and if we can identify biomarkers for even a
subgroup of ASD patients, then that would be extremely helpful not only for
early diagnosis but also for the development of therapeutics," said Dr.
German, whose latest research builds upon an ASD finding published last year
in Scientific Reports
Future Research Plans
research team plans to expand their study in the future
to include the following:
- Testing a bigger set of ASD and TD
samples on the MSD testing platform
- Measuring a total of
four analytes previously identified in the RBM platform (e.g., apolipoprotein E
and stem cell factor along with TSH and IL-8) to assess whether the four
protein analytes combined will provide an accuracy of ~90% in predicting ASD in
boys or an ASD phenotype in a subgroup
- Investigating the
levels of these analytes in much younger children who then went on to develop
conclusion, if these biomarkers are approved, it would increase the chances of
early diagnosis and treatment initiation of ASD with a much better prognosis
for these children in the long-term.
- Sarika Singh, Umar
Yazdani, Bharathi Gadad, Sayed Zaman, Linda S. Hynan, Nichole Roatch, Claire
Schutte, C. Nathan Marti, Laura Hewitson, Dwight C. German. Serum
thyroid-stimulating hormone and interleukin-8 levels in boys with autism
spectrum disorder. Journal of Neuroinflammation, 2017; 14 (1) DOI: