Several studies have shown that conformational changes of beta(2)-glycoprotein I (beta(2)GPI) when bound to negatively charged components expose cryptic epitopes and subsequent binding of anti-beta(2)GPI from patients with antiphospholipid syndrome (APS). However, the role of the carbohydrate chains of beta(2)GPI in this anti-beta(2)GPI reactivity is poorly understood. We therefore studied the reactivity and inhibition of anti-beta(2)GPI antibodies from APS patients with native, partially glycosylated beta(2)GPI (pd beta(2)GPI; without sialic acid) and completely deglycosylated beta(2)GPI (cd beta(2)GPI). To determine the potential biologic importance of these glycoforms and their interaction with anti-beta(2)GPI in vitro, stimulation assays were performed with the U937 cell line. Circular dichroism (CD) and fluorescence analysis of the three beta(2)GPI forms were also studied. We found an increased reactivity of anti-beta(2)GPI against pd beta(2)GPI and cd beta(2)GPI compared to native beta(2)GPI. Both deglycosylated beta(2)GPI isoforms showed higher inhibition of the anti-beta(2)GPI reactivity than the native protein in soluble-phase. Likewise, the antibody/beta(2)GPI/glycoform complexes increased the synthesis of IL-6, IFN gamma and TNF alpha and the expression of HLA-DR, CD14 and CD11c in U937 cells. CD and fluorescence studies of the glycoforms yielded considerable changes in the fluorescence signals. Our work suggests that the partial or complete removal of the carbohydrate chains uncover cryptic epitopes present in beta(2)GPI. The differentiation and increased synthesis of pro-inflammatory cytokines by U937 cells in vitro may have pathogenetic implications. (C) 2014 Elsevier Inc. All rights reserved.