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Background: Moyamoya disease (MMD) is a progressive intracranial arteriopathy of unknown etiology affecting adults and children. We aimed to explore plasma cytokines in pediatric and adult cases of MMD. We hypothesized that quantitative and qualitative differences exist between adults and children, and primary idiopathic versus secondary syndromic cases of MMD.Methods: We performed plasma cytokine analysis using 63-plex Luminex immunoassay on 227 adults, 90% with primary MMD, and 30 children aged <21 years, 80% with primary MMD, from a single center. Patients with a history of stroke within 1-month of plasma collection were excluded. We fitted a linear regression model using pooled data, with adjustment for age and sex, to assess for differences between primary and secondary patients with respect to each of 60 cytokines. We then conducted a stratified analysis by fitting a set of linear regression models for adults and children separately to examine potential interactions between etiology and age. Statistical significance was adjusted using Bonferroni method to account for multiple testing.Results: Three cytokines differed significantly between primary and secondary cases of MMD after Bonferroni correction (p<0.00083), with secondary cases exhibiting higher levels of MCP3 (p=3.8x10-8), IP10 (p=5.1x10-4), and IL12P40 (p=6.4x10-4). Stratified analysis by age identified two cytokines, VEGF (p=7.2x10-4) and IL12P70 (p=7.8x10-4), that differed significantly among children, with higher levels among secondary versus primary MMD, while the difference was not significant among adults (interaction p<2x10-4) (figure 1).Conclusions: Syndromic cases of MMD demonstrate higher levels of plasma cytokines compared to primary cases of MMD, and the difference between primary versus secondary MMD is modified by age for some cytokines. This study suggests the importance of including age and etiology of MMD in investigating biomarkers and disease pathogenesis.