Tumor necrosis factor-alpha expression aberration of M1/M2 macrophages in adult high-functioning autism spectrum disorder

The etiology of autism spectrum disorder (ASD) is complex, and its pathobiology is characterized by enhanced inflammatory activities; however, the precise pathobiology and underlying causes of ASD remain unclear. This study was performed to identify inflammatory indicators useful for diagnosing ASD. The mRNA expression of cytokines, including tumor necrosis factor-alpha (TNF-alpha), was measured in cultured M1 and M2 macrophages from patients with ASD (n = 29) and typically developed (TD) individuals (n = 30). Additionally, TNF-alpha expression in the monocytes of patients with ASD (n = 7), showing aberrations in TNF-alpha expression in M1/M2 macrophages and TD individuals (n = 6), was measured. TNF-alpha expression in M1 macrophages and the TNF-alpha expression ratio in M1/M2 macrophages were markedly higher in patients with ASD than in TD individuals; however, this increase was not observed in M2 macrophages (M1: sensitivity = 34.5%, specificity = 96.7%, area under the curve = 0.74, positive likelihood ratio = 10.34; ratio of M1/M2: sensitivity = 55.2%, specificity = 96.7%, area under the curve = 0.79, positive likelihood ratio = 16.55). Additionally, TNF-alpha expression in monocytes did not significantly differ between patients with ASD and TD individuals. In conclusion, further studies on TNF-alpha expression in cultured macrophages may improve the understanding of ASD pathobiology. Lay Summary TNF-alpha expression in differentiated M1 macrophages and TNF-alpha expression ratio in differentiated M1/M2 macrophages were markedly higher in patients with ASD than in TD individuals, while no difference in TNF-alpha expression was found in pre-differentiation cells such as monocytes. These measurements allow elucidation of the novel pathobiology of ASD and can contribute to biomarker implementation for the diagnosis of adult high-functioning ASD.