# Epigenetic regulation of thrombo-inflammation in Behçet and antiphospholipid syndrome

## TL;DR

The study explores how three microRNAs regulate blood clotting and inflammation in Behçet syndrome and antiphospholipid syndrome, revealing distinct patterns between the two conditions.

## Contribution

The study identifies a unique microRNA signature that discriminates between thrombotic events in Behçet syndrome and antiphospholipid syndrome.

## Key findings

- The three ci-miRNAs (miR-206, miR-224-5p, miR-653-5p) poorly discriminate between BS and APS patients overall.
- In patients with vascular involvement, the combined miRNA signature effectively distinguishes BS from APS and thrombotic APS from healthy controls.
- Thrombin generation assays show distinct clotting profiles between BS and APS, suggesting different epigenetic regulation.

## Abstract

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.

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.

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.

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.

•Three ci-miRNAs are known to regulate thrombo-inflammation in Behçet syndrome (BS).•This ci-miRNA signature is also present in antiphospholipid syndrome (APS).•These ci-miRNA signature discriminates BS with vascular events from thrombotic APS.•Distinct curves in global clotting assay (thrombogram profile) emerge in BS and APS.•Distinct epigenetic factors seem to regulate thrombosis in patients with BS and APS.

Three ci-miRNAs are known to regulate thrombo-inflammation in Behçet syndrome (BS).

This ci-miRNA signature is also present in antiphospholipid syndrome (APS).

These ci-miRNA signature discriminates BS with vascular events from thrombotic APS.

Distinct curves in global clotting assay (thrombogram profile) emerge in BS and APS.

Distinct epigenetic factors seem to regulate thrombosis in patients with BS and APS.