Autism spectrum disorder diagnosis using a new panel of immune- and inflammatory-related serum biomarkers: A case-control multicenter study
Bibliographic record
Abstract
Background and objectives: Children with autism spectrum disorder (ASD) present with distinctive clinical features. No objective laboratory assay has been developed to establish a diagnosis of ASD. Considering the known immunological associations with ASD, immunological biomarkers might enable ASD diagnosis and intervention at an early age when the immature brain has the highest degree of plasticity. This work aimed to identify diagnostic biomarkers discriminating between children with ASD and typically developing (TD) children. Methods: A multicenter, diagnostic case-control study trial was conducted in Israel and Canada between 2014 and 2021. In this trial, a single blood sample was collected from 102 children with ASD as defined in Diagnostic Statistical Manual of Mental Disorders [DSM)-IV (299.00) or DSM-V (299.00)], and from 97 typically developing control children aged 3-12 years. Samples were analyzed using a high-throughput, multiplexed ELISA array which quantifies 1,000 human immune/inflammatory-related proteins. Multiple logistic regression analysis was used to obtain a predictor from these results using 10-fold cross validation. Results: Twelve biomarkers were identified that provided an overall accuracy of 0.82 ± 0.09 (sensitivity: 0.87 ± 0.08; specificity: 0.77 ± 0.14) in diagnosing ASD with a threshold of 0.5. The resulting model had an area under the curve of 0.86 ± 0.06 (95% CI: 0.811-0.889). Of the 102 ASD children included in the study, 13% were negative for this signature. Most of the markers included in all models have been reported to be associated with ASD and/or autoimmune diseases. Conclusion: The identified biomarkers may serve as the basis of an objective assay for early and accurate diagnosis of ASD. In addition, the markers may shed light on ASD etiology and pathogenesis. It should be noted that this was only a pilot, case-control diagnostic study, with a high risk of bias. The findings should be validated in larger prospective cohorts of consecutive children suspected of ASD.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.003 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".