Antiphospholipid antibodies enhance monocyte procoagulant activity in primary antiphospholipid syndrome

ABSTRACT

Fifty cases with unexplained recurrent fetal loss were examined for antiphospholipid antibodies [APA] both by phospholipid-dependent coagulation tests to detect lupus anticoagulant [LA], and by a specific enzyme -linked immunosorbent assay [ELISA]. 18 patients were APA+ve 6 [12%] by coagulation tests [LA+ve] and 12 [24%] by ELISA. Mononuclear cells were isolated from normal healthy volunteers by Ficoll-hypaque and cultured in RPMI-1640 medium [2 x 10[6] cells/ml]. LA+ve plasma, ELISA+ve plasma, and APA-ve control plasma were incubated with cultured cells for 4 hours in presence of lipopolysaccharide [LPS] at a concentration of 100 ng/ml. Significantly higher monocyte procoagulant activity [PCA] was induced by LA+ve and ELISA+ve plasma than by control APA-ve plasma. Immunoglobulin G [IgG] proteins were isolated from patient and control sera by anion exchange chromatography [DEAE Sephadex A50]and were incubated with cultured mononuclear cells under the same conditions. Antiphospholipid IgG [n = 5] induced significantly higher levels of PCA than control IgG [n = 6]. The stimulating effect of APA +ve plasma and antiphospholipid IgG on PCA was not detected in absence of LPS and was dependent on the presence of factor VII, but not factor IX, in the one stage clotting assay of PCA. This indicates that antiphispholipid antibodies probably increase monocyte PCA by enhancing the LPS-stimulated expression of tissue factor [TF]