Methylation was significantly reduced in the IL8 promoter and significantly increased in the F3 gene body in APS patients compared to HDs and correlated with specific clinical parameters.
Regarding epigenetic approaches, we previously recognized two miRNAs (miR-19b/miR-20a) as potential modulators of tissue factor, the main receptor involved in thrombosis development in APS. aPLs can further promote changes in the expression of miRNA biogenesis proteins in leukocytes of APS patients, which are translated into an altered miRNA profile and, consequently, in the altered expression of their protein targets related to thrombosis and atherosclerosis.
Current recommendations advocate for the use of anti-Xa activity monitoring in the setting of APS because of the common laboratory interaction with commercially available tests, such as prothrombin and activated partial thromboplastin times .
For patients with prolonged dRVVT screening times, we evaluated dRVVT results by ISTH and manufacturer's criteria and correlated with the results of other antiphospholipid syndrome (APS) testing (LA-sensitive activated partial thromboplastin time and antiphospholipid antibodies) and with history of thromboembolism and other APS manifestations.
The adjusted odds ratio for t-APS was 2.62 (95%CI 1.03 to 6.62) with TF levels between 50-75th percentiles and 8.62 (95%CI 3.76 to 19.80) with TF levels above the 75th percentile, as compared with the reference category (below the 50th percentile).
All variants were able to inhibit APS-IgG from: binding to whole β2GPI in ELISA, altering the clotting properties of human plasma and promoting thrombosis and tissue factor expression in mice.
The results showed that treatment of anti-β<sub>2</sub>GPI/β<sub>2</sub>GPI or APS-IgG/β<sub>2</sub>GPI complex could markedly induce mTOR activation as well as expression of TF and IL-8 in THP-1 cells or primary monocytes.
Overall, our results indicate that anti-β(2)GPI/β(2)GPI complex induced TF and TNF-α expression involving both TLR4/MyD88 and TLR4/TRIF signaling pathways and TLR4 and its adaptors might be molecular targets for therapy of antiphospholipid syndrome (APS).
The TF expression and activity in the C6(-/-) mice treated with IgG-APS or IgM-APS were diminished when compared to C3H/HeJ (C6(+/+)) mice treated with the same Igs.
Our results suggest that TF/FVIIa/PAR2 signaling mediates neutrophil activation and fetal death in APS and that statins may be a good treatment for women with aPL-induced pregnancy complications.
Interestingly, beta2-GPI expression on monocytes is significantly increased in patients with anti-phospholipid syndrome (APS) or systemic lupus erythematosus (SLE) as against healthy blood donors and correlates with tissue factor expression on monocytes.