Plasma signatures of type 2 inflammation and vascular remodeling in moyamoya disease

Moyamoya disease (MMD) is an idiopathic cerebrovascular disorder in which chronic inflammation has been implicated, along with genetic susceptibility, including the RNF213 variants. In this study, we examined the relationship between type 2 inflammation and MMD.

Blood samples were collected from three groups: 20 patients with MMD, 20 age- and sex-matched unrelated controls, and eight unaffected relatives with the RNF213 p.R4810K variant. Plasma levels of 15 cytokines were quantified using chemiluminescent multiplex ELISA.

IL-13 tended to be higher in patients than in controls, but this difference did not remain significant after correction for multiple comparisons and did not clearly distinguish patients from unaffected carriers. In contrast, IL-5 was significantly higher in patients than in unaffected carrier relatives after multiple-comparison correction (p = 0.0483), as were IL-1β and IL-12p70 (p = 0.00399 and 0.0347). An exploratory model incorporating IL-1β, IL-5, and IL-12p70 yielded an AUC of 0.912 for distinguishing patients from unaffected carriers (p < 0.001). Plasma platelet-derived growth factor-BB (PDGF-BB) levels were significantly lower in patients than in controls and were also lower in the mutant carriers, regardless of whether they developed MMD.

These findings suggest that type 2 and pro-inflammatory cytokine profiles are associated with MMD status among RNF213 p.R4810K carriers. The exploratory multivariable model requires validation in larger independent cohorts.