Objective. To analyze the structure, specificity, and in vivo pathogenetic potential of 2 human anticar-diolipin (aCL) monoclonal antibodies (MAb). Methods. Human aCL IgG MAb were generated from hybridized Epstein-Barr virus-induced B cell lines from a healthy subject (MAb 519) and from a patient with primary antiphospholipid syndrome (MAb 516). Studies of antigen-binding specificity and analysis of Ig V-gene mutations were carried out. The MAb were independently injected into mated female BALBic mice, and their effect on pregnancy outcome was compared with that of MAb 57, a highly mutated and antigen-selected human IgG Ih rabies virus antibody. Results. Both MAb 519 and MAb 516 utilized minimally mutated VHDJH and VJK gene segments and bound cardiolipin and other anionic phospholipids in the absence of P,-glycoprotein I (P,-GPI). The mice injected with aCL MAb displayed a significantly higher rate of fetal resorption and a significant reduction in

SUMMARYThe immunomodulatory effects of the antibiotic sodium fusidate (SF) were tested in a model of T celldependent hepatic injury that can be induced in normal mice by a single i.v. injection of Con A. Signs of hepatitis with elevated transaminase activities in plasma, severe infiltration of the liver by neutrophil granulocytes, lymphocytes and monocytes, and necrotic areas were observed in control mice treated intraperitoneally with PBS 24 h and 1 h before Con A challenge. T cell-and macrophage-derived cytokines (IL-2, interferon-gamma (IFN-g), tumour necrosis factor-alpha (TNF-a), IL-1b, IL-6) were released with different kinetics in the circulation of these mice. SF, 20, 40 or 80 mg/kg, administered 24 h and 1 h before Con A challenge, protected the mice against the hepatitic effects of Con A. The protective effects of SF were dose-dependent and accompanied by profound modifications of blood levels of cytokines induced by Con A, so that, relative to control mice, SF (80 mg/kg)-treated animals showed markedly diminished plasma levels of IL-2, IFN-g and TNF-a, along with augmented levels of IL-6. These results suggest that SF might be useful in the treatment of immunoinflammatory liver diseases in humans.

beta 2-glycoprotein I (beta 2-GP-I) the plasma cofactor for anti-phospholipid antibodies adheres on the endothelial surfaces and can be recognized by anti-beta 2-GP-I antibodies naturally occurring in patients with the anti-phospholipid syndrome. As for the cofactor binding to cardiolipin- or gamma irradiated-plates, the endothelial binding is mediated by the so-called phospholipid binding site, a cationic structure able to react with anionic molecules. Endothelial monolayers appear to represent a substrate able to bind beta 2-GP-I and to present it in a suitable manner in order to allow the binding of anti-beta 2-GP-I beta 2 antibodies. The complex between beta 2-GP-I and the respective antibodies induce an endothelial cell activation as demonstrated by the up-regulation of adhesion molecule expression, the secretion of proinflammatory cytokines and the modulation of arachidonic acid metabolism. Taken together these findings strongly sustain a pivotal role for beta 2-GP-I in allowing antibody deposition on the endothelium and in affecting endothelial cell functions potentially responsible for a procoagulant state.

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