Objective: To determine if elevated rates of
autoimmune disease are present in children with both
Down syndrome and
moyamoya disease given the high rates of
autoimmune disease reported in both conditions and unknown etiology of angiopathy in this population. Methods: A multi-center retrospective case-control study of children with
Down syndrome and
moyamoya syndrome, idiopathic
moyamoya disease, and
Down syndrome without
cerebrovascular disease was performed. Outcome measures included presence of
autoimmune disease, presence of
autoantibodies and angiopathy severity data. Comparisons across groups was performed using the Kruskal-Wallis, χ2 and multivariate Poisson regression. Results: The prevalence of
autoimmune disease were 57.7, 20.3, and 35.3% in persons with
Down syndrome and
moyamoya syndrome, idiopathic
moyamoya disease, and
Down syndrome only groups, respectively (p < 0.001). The prevalence of
autoimmune disease among children with
Down syndrome and
moyamoya syndrome is 3.2 times (p < 0.001, 95% CI: 1.82-5.58) higher than the idiopathic moyamoya group and 1.5 times (p = 0.002, 95% CI: 1.17-1.99) higher than the
Down syndrome only group when adjusting for age and sex. The most common
autoimmune diseases were thyroid disorders, type I diabetes and
Celiac disease. No individuals with idiopathic
moyamoya disease had more than one type of autoimmune disorder while 15.4% of individuals with
Down syndrome and
moyamoya syndrome and 4.8% of individuals with
Down syndrome only had >1 disorder (p = 0.05, 95%CI: 1.08-6.08). Interpretation: This study reports elevated rates of
autoimmune disease in persons with
Down syndrome and
moyamoya syndrome providing a nidus for study of the role of autoimmunity in angiopathy in this population.