Bonferroni correction was applied to adjust for multiple comparisons. of IgA antibodies (p?=?0.007 for IgA aCL and p?=?0.059 for IgA a2GPI). Regarding to APS classification, adding IgA aPL into standard aPL assays may not improve and may even deteriorate the net reclassification index for APS; besides, no association between thrombosis and IgA aPL was observed. Conclusions this study assessed the prevalence of various aPL in Chinese populace. IgA aPL may not enhance the classification ability of established laboratory criteria for thrombotic APS. Our data do not support the addition of IgA aPL to standard aPL assays. Keywords: thrombotic antiphospholipid syndrome, anti-2 glycoprotein I antibody, anticardiolipin antibody, immunoglobulin A, classification Introduction Antiphospholipid syndrome (APS) is usually a systemic autoimmune disease characterized by recurrent thrombotic and/or pregnancy-related morbidity. 1 Early diagnosis is essential to adopting appropriate antithrombotic strategies and preventing the onset of rapidly progressing and potentially life-threatening catastrophic APS. According to the 2006 updated Sapporo classification criteria, patients must meet both clinical and laboratory criteria to receive a diagnosis of APS. 2 Lupus anticoagulant, immunoglobulin (Ig) G/IgM anticardiolipin antibodies (aCL), and IgG/IgM anti-2 SMN glycoprotein I antibodies (a2GPI) are classic antiphospholipid antibodies (aPL) used as laboratory diagnostic markers. However, in practice, some patients with clinical manifestations of APS repeatedly test unfavorable for all these aPL. 3 Accordingly, aPL that are not currently included in the classification criteria, such as IgA aCL and IgA a2GPI, have been proposed as additional indicators to be considered in patients suspected of having seronegative APS. 4 The significance of IgA aPL in the development of thrombotic complications is usually of great interest. Previous studies including a preclinical thrombosis mouse model have exhibited that IgA aCL and a2GPI were able to induce significantly larger thrombi and upregulate the expression of tissue factor.5,6 However, these data cannot show the pathogenicity of IgA aPL because the influence of lupus anticoagulant or IgG aPL cannot be excluded. 7 Some studies have suggested that there may be different subpopulations of a2GPI, each realizing different epitopes on 2GPI and differing greatly in their pathologic effects. 8 For example, IgA a2GPI preferentially targeting the C-terminal portion of 2GPI emerged as harmless in some studies8,9 and as pathogenic in others. 10 Clinical findings around the association between IgA aCL and/or a2GPI and APS-related thrombosis or obstetric complications vary substantially and are sometimes conflicting.11C14 The main factors that contribute to this heterogeneity are the differences in study populations and laboratory methods. Therefore, whether IgA aPL assessments should be part of the routine Trilostane diagnostic algorithm remains subject to debate. Studies with larger and well-characterized populations are required to clarify their clinical value. We have previously reported that IgA aPL may not provide added value in the diagnosis of APS in the Chinese populace. 15 However, that study was restricted to one center, and the 212 APS patients enrolled comprised 127 thrombotic APS patients, 62 obstetric APS patients, and 23 patients with both clinical signs. Emerging data have revealed some important differences between real vascular and obstetric APS variants, which mainly involve a thrombophilic state and inflammation; 16 thus, expanding subgroups of patients for further exploration is necessary. In addition, chemiluminescence immunoassay (CLIA) has become an alternative method to the classical enzyme-linked immunosorbent assay for aPL examination. CLIA has advantages in automation and standardization, 17 which can provide a more stable and comparable Trilostane measure of aPL. In the present two-center study, 122 (43.88%) and 156 (56.12%) patients from northern and southwest China were enrolled, respectively. We focused on patients with clearly defined real thrombotic APS and used CLIA Trilostane for aPL detection to reduce the influence of the study populace and testing method on the results. The present study aimed to obtain convincing evidence on the value of IgA aPL in thrombotic APS diagnosis. Materials and Methods Study Design and Participants This was a retrospective, two-center study. We acquired all the routine IgG/IgM/IgA aPL detection results of participants from Trilostane the West China Hospital (WCH, July 2019 to December 2020) and Peking Union Medical College Hospital (PUMCH, July 2019 to February 2020), using a laboratory information system. After critiquing their basic information, we recruited 12,582 non-duplicate individuals; these participants were considered as the hospital-based general populace. In addition, we enrolled 278 eligible thrombotic APS patients who met the revised Sapporo classification criteria. 2 A total of 233 apparently healthy individuals without infections, tumors, autoimmune diseases, or other inflammatory diseases were included as healthy controls. Baseline demographic and APS-relevant clinical characteristics were extracted from electronic medical records. Comparisons of aPL levels and aPL-positivity rates were performed between the general populace.