A Systematic Scoping Review on the Accuracy of Enzyme-Linked Immunosorbent Assay (ELISA) for Biomarker Detection in the Diagnosis of Autism Spectrum Disorder

OBJECTIVES: Autism spectrum disorder (ASD), a diverse group of neurodevelopmental conditions characterized by deficits in communication, social interaction, and repetitive behavior, is estimated to affect 1 in 36 children. Yet, given the wide variation of symptoms, diagnosis remains challenging and is often late. This study aims to map potential biomarkers for diagnosing ASD in children and adolescents.

METHODS: This study is part of a larger review (DOI 10.17605/OSF.IO/EYV8K), conducted according to Joanna Briggs Institute recommendations. The systematic searches were performed in Pubmed, Embase and Web of Science (February-2024). Primary interventional or observational studies assessing biological markers (e.g., enzymes, molecules, genes) found in body fluids for the diagnosis of ASD were eligible and had their main information extracted. Accuracy data on the methods used to measure biomarkers (including true positive, true negative, false positive, false negative results) were also collected. Whenever possible, meta-analyses of sensitivity and specificity, as well as SROC curves, were built using Metadisc2.0 (results reported with 95% confidence intervals - CI).

RESULTS: From the 86 articles included for evidence synthesis (published between 1986-2023, mainly performed in Asia (55%) and including a total of 37,100 patients), 8 (9.3%) consistently assessed the use of Enzyme-Linked Immunosorbent Assay (ELISA). The meta-analysis revealed an overall sensitivity of 85% (95% CI 79-89) and specificity of 80% (95% CI 57-92) for this test. Included studies reported a specificity of 99% considering thyroxine marker (hormone) and 98% sensitivity for c1q-tnf protein (adipokines family). Other mentioned biomarkers part of the gap mapping included phosfoliapase A and interleucine-6/8.

CONCLUSIONS: The ELISA, a low-cost and easily implemented method, is a promising alternative for aiding in the diagnosis of ASD, especially when targeting serum thyroxine and C1q/TNF-related protein biomarkers, whose expression are elevated in this population. Further studies on the role of these molecules, including their impact on the severity of ASD, are warranted.