Autism Spectrum Disorder – Serum TSH And Interleukin-8 Biomarkers Make Early Diagnosis Possible

Highlights:

• Autism spectrum disorder (ASD) is a neurodevelopmental disorder affecting children with impaired social, cognitive and communication skills, usually diagnosed around the 4th year.
• 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.

Measuring a set of serum protein biomarkers is likely to improve diagnostic accuracy for Autism Spectrum Disorder (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. The study was published in the Journal of Neuroinflammation and is one of the many studies conducted that aim to improve early diagnosis of ASD by shifting focus to measurement of biomarkers, rather than relying on behavioral symptoms for diagnosis.

Why Do We Need Serum Biomarkers For Diagnosis of ASD?

ASD appears to be on the rise with more children being diagnosed with autism than AIDS, cancer and diabetes combined.

Current 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 better outcome.

At present, the diagnosis is made around the age of 4, when communication and social disabilities have progressed enough to be apparent.

Although 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.

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In 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 male children.

Comparing Serum Samples Of ASD Vs TD Boys – The Study

• For the study, 30 boys with ASD and 30 typically developing boys were chosen between the ages of 2-8 years.
• The 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.
• Among the 11, five were identified that showed the highest degree of accuracy. These included TSH, stem cell factor, monocyte chemotactic protein 4, ferritin, and IL-8.
• 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.

Testing TSH And IL-8 On The MSD Platform -- The Findings

• In 43 ASD samples tested, serum TSH levels was 30% lower than in TD samples
• In 36 ASD samples tested, IL-8 levels were found to be 16% higher in ASD boys compared to TD boys.
• 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.
• Lower 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.
• Elevated levels of IL-8 were not associated with ADOS subdomain scores.
• 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.

The 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.

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"ASD is 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

The 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 ASD

In 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.

Reference:

1. 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: 10.1186/s12974-017-0888-4

Source-Medindia