Reduction of regulatory B cells is associated with high-risk clinical stratification in antiphospholipid syndrome patients.

Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by the presence of antiphospholipid antibodies (aPLs). B cells are known to play a crucial role in pathogenesis of APS, however, the contribution of regulatory B cells (Bregs) remains unexplored. Our study aimed to evaluate the changes of Bregs in APS patients, and further explored their potential clinical significance. We comparatively assessed and compared the changes of Bregs (defined as CD19+CD24highCD38high and CD19+CD27+CD24high) among 55 cases of APS patients (including 36 cases of pAPS patients and 19 cases of non-criteria APS patients), 44 systemic lupus erythematosus (SLE) patients, and 30 cases of healthy controls (HCs) using flow cytometry. The adjusted global antiphospholipid syndrome score (aGAPSS) was calculated for the risk stratification of APS patients. Additionally, associations of Bregs with serum aPLs status and aGAPSS were evaluated by correlation analysis or/and receiver operating characteristic (ROC) analysis. We found that APS patients exhibited significantly lower levels of CD19+CD24highCD38highBregs and CD27+CD24highBregs compared with HCs, and were significantly decreased in patients of high-risk (aGAPSS ≥ 10) compared to low-risk patients. In addition, both CD19+CD24highCD38highBregs and CD27+CD24highBregs were inversely correlated with aGAPSS. ROC curve showed that the combination of CD24highCD38highBregs and CD27+CD24highBregs improved the discriminatory performance for identifying high-risk patients (AUC = 0.753), compared with each Bregs alone. Notably, the levels of Bregs were lowest in triple positive aPLs APS patients. In subgroup analyses, a higher frequency of CD24highCD38highBregs was observed in patients with a history of thrombosis. Our results suggested that Bregs may be associated with high-risk aPL profiles and aGAPSS-based risk stratification in APS.