Moyamoya disease emerging as an immune-related angiopathy

Asselman, Caroline; Hemelsoet, Dimitri; Eggermont, Denzel; Dermaut, Bart; Impens, Francis

doi:10.1016/j.molmed.2022.08.009

Cited by 34 publications

(28 citation statements)

References 101 publications

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“…A recent study showed that RNF213 is critical in the ubiquitination of the bacterial lipopolysaccharide and that cells lacking RNF213 suffer from cellular autoimmune deficiency ( 34 ). The RNF213 variant causes reduced E3 ligase activity and ubiquitination, which enhances the stimulation of NFĸB and inflammatory signaling, finally leading to vasculopathy ( 19 ). However, the mechanistic details of RNF213 have not yet been elucidated.…”

Section: Discussionmentioning

confidence: 99%

“…Our previous study also identified the association between rare RNF213 variants and cerebral arteriovenous malformation (cAVM) in a Chinese population ( 18 ). Considering the association of RNF213 with various vascular diseases, the results of studies focusing on the RNF213 and its role in vasculature implied this gene could be a key antimicrobial protein in response to the infectious or autoimmune signaling signals in the process of vascular disease ( 19 ). Till now, several RNF213 variants were identified their association with IA in the French-Canadian population ( 1 ), whereas the study in the German and Japanese populations failed to obtain a significant result, revealing the existence of racial diversity ( 20 , 21 ).…”

Section: Introductionmentioning

confidence: 99%

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Association of rare RNF213 variants and intracranial aneurysm risk in a Chinese population

Li¹,

Liu²,

Hu³

et al. 2022

Ann Transl Med

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Background: Genetic factors play important roles in the development of intracranial aneurysm (IA).Rare RNF213 variants have been identified as being susceptible to Moyamoya disease (MMD), non-MMD intracranial artery stenosis/occlusion disease, and other vascular disorders. This study aimed to investigate the association between rare RNF213 variants and the risk of IA in a Chinese population. Methods:We recruited 174 patients with IA for RNF213 target exome sequencing. Information on the control subjects was obtained from the 1,000 Genome Project and GeneSky in-house database. After prioritizing rare RNF213 variants, the filtered variants were confirmed by Sanger sequencing. Gene-based association analyses were performed to identify the association between variants and the disease using burden and variance component methods; that is, the weighted-sum statistic (WSS) and the sequence kernel association test (SKAT), respectively. The Student's t-test, Chi-squared test, and Fisher's exact test were used to compare the clinical characteristics between carriers and non-carriers of the RNF213 variants.Results: After filtering, there were 14 RNF213 variants in 18 patients with IA, which were significantly associated with the disease after the gene-based association tests [minor allele frequency (MAF) <0.01, WSS P value 5.08×10 -9 ; SKAT P value 2.96×10 -6 ; SKAT-O P value 3.56×10 -8 ]. Significant difference was not obtained between the carriers and non-carriers of the RNF213 variants in terms of the clinical characteristics.Conclusions: Rare RNF213 variants were associated with sporadic IA in a Chinese population. Our findings suggest that these rare RNF213 variants might have potentially important roles in IA. However, more comprehensive studies need to be conducted to confirm this association and causality.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Association of rare RNF213 variants and intracranial aneurysm risk in a Chinese population

Li¹,

Liu²,

Hu³

et al. 2022

Ann Transl Med

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“…A large cohort study of moyamoya disease also showed that autoimmune disease and infection may be potential environmental triggers ( 13 , 14 ). In conclusion, increasing molecular and clinical evidence revealed that immune-inflammation-related responses may be an essential triggering factor of moyamoya disease, just below the genetic factor ( 15 – 18 ).…”

Section: Introductionmentioning

confidence: 90%

Clinical value of the systemic immune-inflammation index in moyamoya disease

Liu

Jin

et al. 2023

Front. Neurol.

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BackgroundMoyamoya disease (MMD) is a rare cerebrovascular disorder with unknown etiology. The underlying pathophysiological mechanism of moyamoya disease remains to be elucidated, but recent studies have increasingly highlighted that abnormal immune response may be a potential trigger for MMD. Neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII) are inflammatory markers that can reflect the immune-inflammation state of the disease.ObjectiveThe purpose of this study was to investigate SII, NLR, and PLR in patients with moyamoya disease.MethodsA total of 154 patients with moyamoya disease (MMD group) and 321 age- and sex-matched healthy subjects (control group) were included in this retrospective case–control study. Complete blood count parameters were assayed to calculate the SII, NLR, and PLR values.ResultsThe SII, NLR, and PLR values in the moyamoya disease group were significantly higher than those in the control group [754 ± 499 vs. 411 ± 205 (P < 0.001), 2.83 ± 1.98 vs. 1.81 ± 0.72 (P < 0.001), and 152 ± 64 vs. 120 ± 42 (P < 0.001), respectively]. The SII in the medium-moyamoya vessels of moyamoya disease was higher than that in the high-moyamoya vessels and low-moyamoya vessels (P = 0.005). Using the receiver operating characteristic (ROC) curve analysis to predict MMD, the highest area under the curve (AUC) was determined for SII (0.76 for SII, 0.69 for NLR, and 0.66 for PLR).ConclusionBased on the results of this study, patients with moyamoya disease admitted for inpatient care due to acute or chronic stroke have significantly higher SII, NLR, and PLR when compared to blood samples drawn from completely healthy controls in a non-emergent outpatient setting. While the findings may suggest that inflammation plays a role in moyamoya disease, further studies are warranted to corroborate such an association. In the middle stage of moyamoya disease, there may be a more intense imbalance of immune inflammation. Further studies are needed to determine whether the SII index contributes to the diagnosis or serves as a potential marker of an inflammatory response in patients with moyamoya disease.

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“…MMD is a leading cause of stroke for both children and young adult, while the etiology remains largely unclear. Genetic studies have identified RNF213, as a susceptibility gene for MMD, but the low penetrance in genetically susceptible individuals suggests that a second hit is necessary to trigger disease onset (Asselman et al., 2022).…”

Section: Introductionmentioning

confidence: 99%