“Non-criteria” antiphospholipid antibodies aid risk stratification in autoimmune recurrent pregnancy loss

Recurrent pregnancy loss (RPL) is a serious pregnancy disease caused by a variety of factors. Obstetric antiphospholipid syndrome (OAPS) is the most prevalent treatable cause of RPL. Although some RPL patients do not meet the diagnosis of OAPS, they may benefit from the standard treatment of OAPS. However, the diagnosis and treatment of these patients are controversial. To evaluate the value of “non-criteria” antiphospholipid antibodies (aPLs) in RPL patients, and to assess whether RPL patients with “criteria”/ “non-criteria” aPL positivity could benefit from treatment with low-molecular-weight heparin (LMWH) and low-dose aspirin (LDA), we profiled five “criteria” and ten “non-criteria” aPLs, namely LA, aCL IgG/M, aβ2GPI IgG/M, aPS/PT IgG/M, aANXA5, aANXA2, aVIM, aβ2GPI-D1, aPE, aPI IgG/M, aPS IgG, in 11 OAPS, 65 “non-criteria” OAPS (NOAPS), 31 OAPS carrier, 90 connective tissue disease-RPL (CTD-RPL), 75 unexplained RPL (URPL), 45 thrombotic APS (TAPS) patients, and 81 healthy controls (HCs). Our results showed that aPS/PT IgG/M, aANXA5, aANXA2, aVIM, aβ2GPI-D1, aPE, aPI IgG/M, and aPS IgG were associated with RPL. We found that aPS/PT IgG was positively correlated with the number of “criteria” aPL positivity in APS patients. Importantly, “non-criteria” aPL-positive RPL patients could benefit from the treatment with LMWH and LDA. Combined aPE, aANXA2, aVIM, and aβ2GPI-D1 could distinguish OAPS, NOAPS, OAPS carrier, CTD-RPL, and URPL group from HCs. Our study demonstrates the utility of “non-criteria” aPLs in identifying RPL women with clinical features of OAPS, which is expected to provide tailored treatment management for RPL patients and ultimately improve obstetric outcomes.