Alessandra Bettiol , Giacomo Bagni , Francesca Di Patti , Elena Lastraioli , Alice Barinotti , Massimo Radin , Savino Sciascia , Domenico Prisco , Annarosa Arcangeli , Giacomo Emmi
{"title":"Epigenetic regulation of thrombo-inflammation in Behçet and antiphospholipid syndrome","authors":"Alessandra Bettiol , Giacomo Bagni , Francesca Di Patti , Elena Lastraioli , Alice Barinotti , Massimo Radin , Savino Sciascia , Domenico Prisco , Annarosa Arcangeli , Giacomo Emmi","doi":"10.1016/j.jtauto.2025.100293","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>An epigenetic regulation of thrombo-inflammation has been reported in Behçet syndrome (BS), likely driven by a unique profile of three plasmatic circulating microRNAs (ci-miRNAs) (miR-206, miR-224-5p, and miR-653-5p). We compared this ci-miRNAs expression in BS and antiphospholipid syndrome (APS), the prototype of acquired pro-thrombotic autoimmune disease. To further corroborate the hypothesis that shared mechanisms drive the thrombotic process in BS and APS, we further assessed their thrombin generation assay (TGA) profile.</div></div><div><h3>Methods</h3><div>The three ci-miRNA expression was evaluated in 39 patients with BS, 33 with APS and 30 healthy controls (HCs). Single marker and combined ROC curve analyses were performed. TGA was conducted on pre-collected platelet poor plasma samples from 35 patients with BS and 77 with APS.</div></div><div><h3>Results</h3><div>The three ci-miRNAs, taken individually or combined, lacked acceptable discriminating power between groups [AUC from combiROC 0.64 (95 % CI: 0.51–0.78)]. Conversely, in the subgroups of BS and APS patients with vascular involvement (n = 22 each), the combined signature well discriminated between the two syndromes [AUC 0.83 (0.71–0.96), specificity 0.91, sensitivity 0.77], as well as between thrombotic APS and HCs [AUC 0.79 (0.64–0.91)]. Also, distinct trends in thrombograms emerged between BS and APS, with BS TGA displaying lower tLag and tPeak, higher Peak and similar AUC as compared to APS.</div></div><div><h3>Conclusions</h3><div>Despite shared elements in the ci-miRNA regulation of their pro-thrombotic tendency, distinct epigenetic factors seem to contribute to the pathogenesis of vascular events in BS and APS, possibly accounting also for the different global clotting assay observed in these diseases.</div></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"11 ","pages":"Article 100293"},"PeriodicalIF":3.6000,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Translational Autoimmunity","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2589909025000280","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Background
An epigenetic regulation of thrombo-inflammation has been reported in Behçet syndrome (BS), likely driven by a unique profile of three plasmatic circulating microRNAs (ci-miRNAs) (miR-206, miR-224-5p, and miR-653-5p). We compared this ci-miRNAs expression in BS and antiphospholipid syndrome (APS), the prototype of acquired pro-thrombotic autoimmune disease. To further corroborate the hypothesis that shared mechanisms drive the thrombotic process in BS and APS, we further assessed their thrombin generation assay (TGA) profile.
Methods
The three ci-miRNA expression was evaluated in 39 patients with BS, 33 with APS and 30 healthy controls (HCs). Single marker and combined ROC curve analyses were performed. TGA was conducted on pre-collected platelet poor plasma samples from 35 patients with BS and 77 with APS.
Results
The three ci-miRNAs, taken individually or combined, lacked acceptable discriminating power between groups [AUC from combiROC 0.64 (95 % CI: 0.51–0.78)]. Conversely, in the subgroups of BS and APS patients with vascular involvement (n = 22 each), the combined signature well discriminated between the two syndromes [AUC 0.83 (0.71–0.96), specificity 0.91, sensitivity 0.77], as well as between thrombotic APS and HCs [AUC 0.79 (0.64–0.91)]. Also, distinct trends in thrombograms emerged between BS and APS, with BS TGA displaying lower tLag and tPeak, higher Peak and similar AUC as compared to APS.
Conclusions
Despite shared elements in the ci-miRNA regulation of their pro-thrombotic tendency, distinct epigenetic factors seem to contribute to the pathogenesis of vascular events in BS and APS, possibly accounting also for the different global clotting assay observed in these diseases.