Background/Purpose: Anticoagulant, antiplatelet or immunosuppressive therapy are currently used to treat the clinical manifestations of the anti-phospholipid syndrome (APS). Side effects or recurrences in spite of the therapy suggest to develop new therapeutic tools.

Methods: We have developed a human minibody containing a single chain fragment variable fused to IgG1 CH2-CH3 domain that recognizes  domain I of β2GPI from humans and other animal species.

Results: The minibody is pathogenic inducing clot formation and fetal loss in naive mice. Its biologic effect is complement-mediated as suggested by its ability to promote in-vitro and in-vivo complement deposition and its failure to induce thrombosis in C6 deficient rats and fetal loss in C5 depleted mice. We have further developed a CH2-domain-deleted minibody with the same antigen specificity but that does not activate complement. The minibody variant does not cause vessel occlusion and pregnancy loss and fails to promote complement deposition in mice. The CH2-deleted minibody is able to displace patients’ antibodies bound to β2GPI and its passive infusion prevents fetal loss and clot formation induced by the anti-β2GPI antibodies from APS patients.

Conclusion:  Our finding pave the way for the use of non pathogenic monoclonal antibody able to compete with the pathogenic polyclonal anti-β2GPI antibodies supporting its potential therapeutic use in patients with APS.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/a-human-monoclonal-antibody-against-domain-i-of-%ce%b22-glycoprotein-i-prevents-clotting-and-fetal-loss-induced-by-polyclonal-anti-phospholipid-antibodies-in-animal-models/