Increased Autoimmunity in Individuals With Down Syndrome and Moyamoya Disease

Abstract

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.

Immunotherapy Responsiveness and Risk of Relapse in Down Syndrome Regression Disorder

“…This is supported the observed 4.34 times greater risk of relapse in individuals with neurodiagnostic study abnormalities (including early/accelerated mineralization and CSF abnormalities) which are indicative of potentially interferon driven immune dysregulation, a concept more well established in systemic disease presentations in persons with DS [15][16][17][18] . It has been established that individuals with DS are at great risk for a variety of autoimmune disorders [19][20][21][22][23][24][25] , and thus it would be reasonable to consider the brain as another potential target of immune dysregulation. This study is not without limitations.…”

Current Understanding of Moyamoya Disease (MMD) and Associated Neuropsychiatric Outcomes

“…Down syndrome, neurofibromatosis type 1, and several other genetic mutations are associated with the genetic predisposition of MMS. 20 Sixteen genes and several pathways, including the Ras and MAPK, Notch, DNA repair, inflammasome, chromatin remodeling, actin remodeling, coagulation, and nitric oxide (NO) pathways, are involved in moyamoya angiopathy ( Figure 3 ). 7 Literature suggests that RNF213 is the primary gene associated with moyamoya angiopathy.…”

“…Advancements in imaging techniques integrating DSA, MRI, and cerebrovascular reserve capacity have led to the recently validated Berlin grading system which has proven superior to the traditional Suzuki staging system. 20 , 21 This allows clinicians to evaluate the hemodynamic status while stratifying the individual risks associated with surgery, as opposed to basing clinical decisions strictly on cerebrovascular morphology. 20 , 21 Other researchers have suggested that quantitative MRI-based methods and Doppler may be beneficial in MMD diagnosis and evaluation.…”

“… 20 , 21 This allows clinicians to evaluate the hemodynamic status while stratifying the individual risks associated with surgery, as opposed to basing clinical decisions strictly on cerebrovascular morphology. 20 , 21 Other researchers have suggested that quantitative MRI-based methods and Doppler may be beneficial in MMD diagnosis and evaluation. Both imaging techniques evaluate cerebral perfusion without requiring contrast media or exposing patients to ionizing radiation.…”

Moyamoya syndrome with ruptured aneurysm in α‑thalassemia: A case report

“…1C and D ). Other disorders associated with MMS, such as vasculitis ( 8 ), autoimmune disease ( 9 ), infection ( 10 ) and thrombophilia ( 11 ), were excluded through medical history, physical examination and relevant blood tests. The patient was duly diagnosed with moyamoya disease (MMD) with aneurysm rupture and bleeding.…”