Anti-GalNAcβ : a novel anti-glycan autoantibody associated with pregnancy loss in women with antiphospholipid syndrome and in a mouse experimental model

OBJECTIVES: We evaluated the presence of anti-glycan antibodies (aGA) in patients with antiphospholipid syndrome (APS), and associations between aGA and clinical features of the disease. METHODS: Sera from APS patients and healthy controls were analyzed for aGA levels by ELISA. Analysis of the association of specific aGA with clinical manifestations of APS was performed. Selected aGA were affinity-purified and injected intravenously into naive mice which were tested for fetal loss. Matrigel invasion assay was performed for detection of choriocarcinoma cells (JAR) invasion and proliferation in the presence of selected aGA. Culture fluid of JAR invasion assays was analyzed for the presence of MMP2 and MMP9. RESULTS: High levels of several aGA were found in APS sera, of which anti-GalNAc-β was significantly associated with recurrent pregnancy loss. Naive mice infused intravenously with anti-GalNAc-β developed increased fetal loss. Anti-GalNAc-β significantly inhibited the in-vitro percentage of JAR invasiveness and the secretion of MMP2 and MMP9 by human JAR cells. CONCLUSIONS: APS sera contain significant levels of aGA directed against several glycans. Anti-GalNAc-β Ab is specifically associated with recurrent pregnancy loss both in human patients and experimental mouse model. The pathogenic effects of anti-GalNAc-β include inhibition of JAR cells invasiveness accompanied by decreased MMP2 and MMP9 secretion