Discovery of a novel cytokine signature for the diagnosis of autism spectrum disorder in young Arab children in Qatar

Wared Nour-Eldine; Nimshitha Pavathuparambil Abdul Manaph; Samia M Ltaief; Nazim Abdel Aati; Monaa Hussain Mansoori; Samya Al Abdulla; Abeer R Al-Shammari

doi:10.3389/fpsyt.2024.1333534

Discovery of a novel cytokine signature for the diagnosis of autism spectrum disorder in young Arab children in Qatar

Front Psychiatry. 2024 Feb 13:15:1333534. doi: 10.3389/fpsyt.2024.1333534. eCollection 2024.

Authors

Wared Nour-Eldine¹, Nimshitha Pavathuparambil Abdul Manaph¹, Samia M Ltaief¹, Nazim Abdel Aati², Monaa Hussain Mansoori³, Samya Al Abdulla³, Abeer R Al-Shammari¹

Affiliations

¹ Neurological Disorders Research Center, Qatar Biomedical Research Institute, Hamad Bin Khalifa University, Qatar Foundation, Doha, Qatar.
² Child Development Center, Rumailah Hospital, Hamad Medical Corporation, Doha, Qatar.
³ Department of Operations, Primary Health Care Corporation, Doha, Qatar.

Abstract

Background: Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental disorder characterized by impaired social interaction and communication and the occurrence of stereotyped and repetitive behaviors. Several studies have reported altered cytokine profiles in ASD and hence may serve as potential diagnostic biomarkers of the disorder. This study aims to identify diagnostic biomarkers for ASD in a well-defined study cohort in Qatar.

Methods: We measured the protein levels of 45 cytokines in the plasma samples of age- and gender-matched children (2-4 years) with ASD (n = 100) and controls (n = 60) using a Luminex multiplex assay. We compared the differences in the levels of these cytokines between the two study groups and then fitted the significantly altered cytokines into a logistic regression model to examine their diagnostic potential for ASD.

Results: We found elevated levels of IFN-γ, FGF-2, IL-1RA, and IL-13 and reduced levels of eotaxin, HGF, IL-1 alpha, IL-22, IL-9, MCP-1, SCF, SDF-1 alpha, VEGFA, and IP-10 in the plasma of children with ASD compared to controls. Furthermore, we observed that elevated levels of IFN-γ (odds ratio (OR) = 1.823; 95% (confidence interval) CI = 1.206, 2.755; p = 0.004) and FGF-2 (OR = 2.528; 95% CI = 1.457, 4.385; p < 0.001) were significantly associated with increased odds of ASD, whereas reduced levels of eotaxin (OR = 0.350; 95% CI = 0.160, 0.765; p = 0.008) and HGF (OR = 0.220; 95% CI = 0.070, 0.696; p = 0.010) were significantly associated with lower odds of ASD relative to controls. The combination of these four cytokines revealed an area under the curve (ROC-AUC) of 0.829 (95% CI = 0.767, 0.891; p < 0.001), which demonstrates the diagnostic accuracy of the four-cytokine signature.

Conclusions: Our results identified a panel of cytokines that could discriminate between children with ASD and controls in Qatar. In addition, our findings support the predominance of a Th1 immune phenotype in ASD children and emphasize the need to validate these results in larger populations.

Keywords: ASD; autism spectrum disorder; biomarkers; cytokines; logistic regression; luminex multiplex assay.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by an ECRA Award (number ECRA01-001-3-001) from the Qatar National Research Fund (a member of the Qatar Foundation) and a start-up fund from the Qatar Biomedical Research Institute (grant code VR03).