Background: The aim of the study was to determine the prevalence and clinical associations of antiphosphatidylserine/prothrombin antibodies (aPS/PT) with thrombosis and pregnancy loss in Chinese patients with antiphospholipid syndrome (APS) and seronegative APS (SNAPS). Methods: One hundred and eighty six Chinese patients with APS (67 primary, 119 secondary), 48 with SNAPS, 176 disease controls (79 systemic lupus erythematosus [SLE], 29 Sjogren’s syndrome [SS], 30 ankylosing spondylitis [AS], 38 rheumatoid arthritis [RA]) and 90 healthy donors were examined. IgG and IgM aPS/PT, IgG/IgM/IgA anticardiolipin (aCL) and IgG/IgM/IgA anti-β₂-glycoprotein I (anti-β2GPI) antibodies were tested by ELISA. Results: One hundred and sixty (86.0%) of APS patients were positive for at least one aPS/PT isotype. One hundred and thirty five (72.6%) were positive for IgG aPS/PT, 124/186 (66.7%) positive for IgM aPS/PT and 99 (53.2%) positive for both. Approximately half of the SNAPS patients were positive for IgG and/or IgM aPS/PT. Highly significant associations between IgG aPS/PT and venous thrombotic events (odds ratio [OR]=6.72) and IgG/IgM aPS/PT and pregnancy loss (OR=9.44) were found. Levels of IgM aPS/PT were significantly different in APS patients with thrombotic manifestations and those with fetal loss (p=0.014). The association between IgG/IgM aPS/PT and lupus anticoagulant (LAC) was highly significant (p<0.001). When both were positive, the OR for APS was 101.6. Notably, 91.95% (80/87) of LAC-positive specimens were positive for IgG and/or IgM aPS/PT, suggesting aPS/PT is an effective option when LAC testing is not available. Conclusions: Anti-PS/PT antibody assays demonstrated high diagnostic performance for Chinese patients with APS, detected some APS patients negative for criteria markers and may serve as potential risk predictors for venous thrombosis and obstetric complications.

Integrins coupled with other proteins form protein complexes named focal adhesions (FA) which are considered as the primary sites for cellular forces transduction during cell stable adhesion. Cell traction forces transmitted by FAs and integrin tensions inside FAs have been extensively studied. However, it remains unknown whether integrins outside FAs can transmit tension, and if so, what is the tension range. We previously developed a tension sensor named tension gauge tether (TGT). To calibrate integrin tensions outside FAs, here we applied multiplex TGT (mTGT) to simultaneously monitor integrin tensions at separate levels. mTGT unambiguously revealed that integrins outside FAs also transmit tension after FA formation. These tensions are mainly located in the range of 43 ~ 54 pN which is lower than integrin tensions inside FAs. Integrin tensions both inside and outside FAs substantially contribute to bulk cellular forces and they respond independently to actin and myosin II inhibition, serum deprivation and microtubule inhibition, indicating their different tension sources and independent dynamics. Our work identified integrin tensions outside FAs and calibrated the tension range for the first time. We also demonstrated that mTGT is a valuable tool to monitor integrin tension profile in a broad detection range of 10 ~ 60 pN.