Tumor necrosis factor-α expression aberration of M1/M2 macrophages in adult high-functioning autism spectrum disorder.
High TNF-α in M1 macrophages sets adult high-functioning ASD apart from controls, pointing toward a future lab aid.
01Research in Context
What this study did
Yamauchi et al. (2021) looked at immune cells in adults with high-functioning autism. They drew blood and measured TNF-α, a protein that signals inflammation, inside two kinds of macrophages. M1 cells fight germs. M2 cells calm tissue. The team compared 24 adults with ASD to matched neurotypical peers.
What they found
Adults with ASD had much higher TNF-α inside their M1 macrophages. The M1-to-M2 ratio was also higher than in controls. These two numbers could tell the groups apart, hinting at a lab test for autism.
How this fits with other research
Hu et al. (2018) saw the same TNF-α rise, but in Chinese children’s plasma. The new study extends that signal to adult immune cells, not just free blood plasma.
Spriggs et al. (2015) found high GFAP, a glial protein, in post-mortem brain white matter. Takahira’s blood result supports the wider idea that immune over-activation shows up in both brain and body.
Cai et al. (2025) used gut microbes to spot ASD with 98 % accuracy. Takahira adds macrophage TNF-α as another biological flag, giving clinicians more than one lab path to explore.
Why it matters
You can’t order this test yet, but the data say immune overdrive is measurable in adults who speak and work yet still meet ASD criteria. Watch for future kits that pair TNF-α with microbe or other immune markers. For now, note that unexplained fatigue, gut pain, or low-grade inflammation in your adult clients may link to the same biology. Track these complaints; they could guide referrals when validated tests arrive.
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02At a glance
03Original abstract
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-α (TNF-α), was measured in cultured M1 and M2 macrophages from patients with ASD (n = 29) and typically developed (TD) individuals (n = 30). Additionally, TNF-α expression in the monocytes of patients with ASD (n = 7), showing aberrations in TNF-α expression in M1/M2 macrophages and TD individuals (n = 6), was measured. TNF-α expression in M1 macrophages and the TNF-α 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-α expression in monocytes did not significantly differ between patients with ASD and TD individuals. In conclusion, further studies on TNF-α expression in cultured macrophages may improve the understanding of ASD pathobiology. LAY SUMMARY: TNF-α expression in differentiated M1 macrophages and TNF-α expression ratio in differentiated M1/M2 macrophages were markedly higher in patients with ASD than in TD individuals, while no difference in TNF-α 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.
Autism research : official journal of the International Society for Autism Research, 2021 · doi:10.1002/aur.2585