Neuregulin 2 and tubulin protein levels in children with autism spectrum disorder

Multiple lines of evidence suggest that neuregulin 2 (NRG2) and tubulin play important roles in the neuron cytoskeleton, neuronal development, synaptic plasticity, and downstream signaling pathways implicated in autism spectrum disorder (ASD). This study aimed to investigate plasma levels of NRG2 and tubulin in ASD and to examine their association with the ASD severity and social impairment. Plasma levels of NRG2 and tubulin were measured using a sandwich enzyme immunoassay in 40 children with ASD and 40 age-matched healthy controls. Autism severity and social impairment were evaluated by the childhood autism rating scale (CARS) and Social Responsiveness Scale (SRS) respectively. Receiver operating characteristic (ROC) curve analysis was performed to determine the area under the curve (AUC), and Spearman’s correlation coefficients (r) were calculated to examine the relationships between NRG2 and tubulin levels and CARS, SRS, and age using SPSS. Significantly decreased plasma levels of NRG2 were observed in children with ASD ( n = 40, 4.27 ± 0.26 ng/ml [mean ± SEM]) compared with healthy controls ( n = 40, 5.44 ± 0.42 ng/ml, [mean ± SEM], p < 0.05). Similarly, plasma tubulin levels were significantly lower in children with ASD ( n = 37, 3.65 ± 0.42 ng /ml) than in healthy controls ( n = 38, 6.05 ± 0.48 ng /ml), [mean ± SEM], p < 0.05). Segregation of children with ASD into ASD level 2 and ASD level 3 autism revealed that both the ASD level 2 ( n = 17, 3.03 ± 0.40 ng /ml, p = 0.001) and ASD level 3 group ( n = 20, 4.18 ± 0.57 ng /ml p = 0.01) had significantly lower tubulin levels ( p < 0.05), compared with control children. NRG2 was significantly positively correlated with SRS scores (r = 0.434, p = 0.005), whereas tubulin exhibited significant diagnostic accuracy (AUC = 0.743, 95% CI [0.146–0.369], p < 0.001). Our findings highlight the potential involvement of NRG2 and tubulin in the pathophysiology of ASD, particularly in relation to neuronal development and synaptic function. Their association with social ability of children with ASD and diagnostic sensitivity suggests that they may serve as promising candidate biomarkers. Further large-scale studies are needed to confirm these findings and clarify their roles in ASD pathogenesis.