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. 2021 Nov 6;20(1):155.
doi: 10.1186/s12944-021-01578-7.

Alpha-Synuclein, cyclooxygenase-2 and prostaglandins-EP2 receptors as neuroinflammatory biomarkers of autism spectrum disorders: Use of combined ROC curves to increase their diagnostic values

Afaf El-Ansary  1   2 , Manan Alhakbany  3 , Abeer Aldbass  4 , Hanan Qasem  5 , Sarah Al-Mazidi  5 , Ramesa Shafi Bhat  5 , Laila Al-Ayadhi  6   3
Affiliations

Alpha-Synuclein, cyclooxygenase-2 and prostaglandins-EP2 receptors as neuroinflammatory biomarkers of autism spectrum disorders: Use of combined ROC curves to increase their diagnostic values

Afaf El-Ansary et al. Lipids Health Dis. .

Erratum in

Abstract

Background: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impairments in social interaction and restricted and repetitive behaviors. Neuroinflammation and abnormal lipid mediators have been identified in multiple investigations as an acknowledged etiological mechanism of ASD that can be targeted for therapeutic intervention.

Methods: In this study, multiple regression and combined receiver operating characteristic (ROC) curve analyses were used to determine the relationship between the neuroinflammatory marker α-synuclein and lipid mediator markers related to inflammation induction, such as cyclooxygenase-2 and prostaglandin-EP2 receptors, in the etiology of ASD. Additionally, the study aimed to determine the linear combination that maximizes the partial area under ROC curves for a set of markers. Forty children with ASD and 40 age- and sex-matched controls were enrolled in the study. Using ELISA, the levels of α-synuclein, cyclo-oxygenase-2, and prostaglandin-EP2 receptors were measured in the plasma of both groups. Statistical analyses using ROC curves and multiple and logistic regression models were performed.

Results: A remarkable increase in the area under the curve was observed using combined ROC curve analyses. Moreover, higher specificity and sensitivity of the combined markers were reported.

Conclusions: The present study indicates that measurement of the predictive value of selected biomarkers related to neuroinflammation and lipid metabolism in children with ASD using a ROC curve analysis should lead to a better understanding of the etiological mechanism of ASD and its link with metabolism. This information may facilitate early diagnosis and intervention.

Keywords: Autism; Cyclooxygenase-2; Neuroinflammation; Prostaglandin-EP2 receptors; α-Synuclein.

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Conflict of interest statement

The authors have no competing interests to declare.

Figures

Fig. 1
Fig. 1
Pearson’s correlation of PGE2-EP2 and COX-2 patients and control healthy groups. Scatter plots depicted correlation of both variables with, the best fit negative correlation in a group of 40 patients (Up), and the best fit positive correlation curve in a group of 40 healthy control participants (Down)
Fig. 2
Fig. 2
Receiver operating characteristic curve (ROC) for prediction of ASD based on the plasma levels of a PGE2-EP2, b COX-2, c α-Syn measured by ELISA, AUC (Area under the curve); PGE2-EP2: 0.875; COX-2: 0.776; α-Syn: 0.609
Fig. 3
Fig. 3
Receiver operating characteristic curves (ROC) for prediction of ASD based on the plasma levels of combining (a) PGE2-EP2 with COX-2, (b) COX-2 with α-Syn, (c) PGE2-EP2 with α-Syn, and (d) PGE2-EP2 with COX-2 and α-Syn in the patient group. AUC(Area under the curve); PGE2-EP2 with COX-2: 0.921; COX-2 with α-Syn: 0.891, PGE2-EP2 with α-Syn: 0.917; PGE2-EP2 with COX-2 and α-Syn: 0.938
Fig. 4
Fig. 4
Predictiveness curve as graphical representation of the distribution of risk in the patient group by combining plasma (a) PGE2-EP2 with COX-2, (b) PGE2-EP2 with α-Syn, (c) COX-2 with α-Syn, and (d) PGE2-EP2 with COX-2 with α-Syn. The horizontal line of reference corresponds to the prevalence of the disease. The x axis represents the risk percentiles. The y axis represents the probability of identifying the disease
Fig. 5
Fig. 5
Illustration of the relationship between α-Syn, COX-2, and PGE2/EP2 in inducing glutamate excitotoxicity and PGE2/EP2 shedding as etiological mechanisms of ASD
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References

    1. Bhatia MS, Rajender G, Malhotra S, Kanwal K, Chaudhary D. Current understanding of neurobiology of autism spectrum disorders and its nosological implications. Delhi Psychiatry J. 2010;13:18–28.
    1. Tchaconas A, Adesman A. Autism spectrum disorders: a pediatric overview and update. Curr Opin Pediatr. 2013;25:130–144. doi: 10.1097/MOP.0b013e32835c2b70. - DOI - PubMed
    1. Andoh M, Ikegaya Y, Koyama R. Microglia as possible therapeutic targets for autism spectrum disorders. Prog Mol Biol Transl Sci. 2019;167:223–245. doi: 10.1016/bs.pmbts.2019.06.012. - DOI - PubMed
    1. Bilbo SD, Block CL, Bolton JL, Hanamsagar R, Tran PK. Beyond infection -Maternal immune activation by environmental factors, microglial development, and relevance for autism spectrum disorders. Exp Neurol. 2018;299(Pt A):241–251. doi: 10.1016/j.expneurol.2017.07.002. - DOI - PMC - PubMed
    1. Abruzzo PM, Ghezzo A, Bolotta A, Ferreri C, Minguzzi R, Vignini A, et al. Perspective biological markers for autism Spectrum disorders:advantages of the use of receiver operating characteristic curves in evaluating marker sensitivity and specificity. Dis Markers. 2015;329607. 10.1155/2015/329607. - PMC - PubMed