Pathogenesis and Treatment of the Antiphospholipid Syndrome
Pathogenesis and Treatment of the Antiphospholipid Syndrome
Purpose of review Many advancements in our understanding of the pathogenic mechanisms of the antiphospholipid syndrome (APS) have been accomplished over the recent months. Such progresses are paralleled by the development of innovative pharmacological tools that could provide novel therapeutic windows in APS management. The most recent and innovative findings about the biologic effects of antiphospholipid antibodies (aPLs) and the treatment APS will be hereby critically appraised.
Recent findings Antibodies against the domain I of β2 glycoprotein I (β2GPI) are increasingly recognized as the main pathogenic subset; pioneer therapeutic options exploiting the pathogenicity of anti-domain I antibodies have been developed. AnnexinA2 and toll-like receptor (TLR)4 have been identified as the main receptors for β2GPI/anti-β2GPI antibodies on target cells; additional co-receptors might include TLR1, TLR2 and TLR6. Upon binding, aPLs engage intracellular mediators as nuclear factor kappa B and mammalian target of rapamycin, which provide potential therapeutic targets. Current innovative treatment options include novel oral anticoagulants and the complement inhibitor eculizumab. The addition to standard treatment of pleiotropic agents such as hydroxychloroquine, statins and vitamin D could allow better disease control.
Summary The lively and intense research in the APS field opens new frontiers in aPL pathogenic mechanisms, as well as diagnosis and treatment of the syndrome.
Video abstract: http://links.lww.com/COR/A26.
The updated classification criteria of the antiphospholipid syndrome (APS) require a history of vascular thrombosis and/or pregnancy morbidity in the persistent positivity for serum antiphospholipid antibodies (aPLs). The laboratory detection of circulating aPLs still relies on the solid-phase assays for antibodies against cardiolipin (aCL) and β2 glycoprotein I (anti-β2GPI antibodies) and the functional test lupus anticoagulant. None of the emerging aPL assays nor any of the several manifestations increasingly recognized as part of the APS spectrum are thus considered in these criteria, which date back to 2006. Therefore, the formal laboratory and clinical diagnosis of APS does not yet take into account the many advancements in the APS field, which have been allowing the progressive identification of new potential diagnostic markers, the unravelling of aPL antibody-mediated pathogenic mechanisms and the development of novel therapeutic strategies. The most recent and innovative findings about aPL biologic effects and APS treatment will be hereby critically appraised.
Abstract and Introduction
Abstract
Purpose of review Many advancements in our understanding of the pathogenic mechanisms of the antiphospholipid syndrome (APS) have been accomplished over the recent months. Such progresses are paralleled by the development of innovative pharmacological tools that could provide novel therapeutic windows in APS management. The most recent and innovative findings about the biologic effects of antiphospholipid antibodies (aPLs) and the treatment APS will be hereby critically appraised.
Recent findings Antibodies against the domain I of β2 glycoprotein I (β2GPI) are increasingly recognized as the main pathogenic subset; pioneer therapeutic options exploiting the pathogenicity of anti-domain I antibodies have been developed. AnnexinA2 and toll-like receptor (TLR)4 have been identified as the main receptors for β2GPI/anti-β2GPI antibodies on target cells; additional co-receptors might include TLR1, TLR2 and TLR6. Upon binding, aPLs engage intracellular mediators as nuclear factor kappa B and mammalian target of rapamycin, which provide potential therapeutic targets. Current innovative treatment options include novel oral anticoagulants and the complement inhibitor eculizumab. The addition to standard treatment of pleiotropic agents such as hydroxychloroquine, statins and vitamin D could allow better disease control.
Summary The lively and intense research in the APS field opens new frontiers in aPL pathogenic mechanisms, as well as diagnosis and treatment of the syndrome.
Video abstract: http://links.lww.com/COR/A26.
Introduction
The updated classification criteria of the antiphospholipid syndrome (APS) require a history of vascular thrombosis and/or pregnancy morbidity in the persistent positivity for serum antiphospholipid antibodies (aPLs). The laboratory detection of circulating aPLs still relies on the solid-phase assays for antibodies against cardiolipin (aCL) and β2 glycoprotein I (anti-β2GPI antibodies) and the functional test lupus anticoagulant. None of the emerging aPL assays nor any of the several manifestations increasingly recognized as part of the APS spectrum are thus considered in these criteria, which date back to 2006. Therefore, the formal laboratory and clinical diagnosis of APS does not yet take into account the many advancements in the APS field, which have been allowing the progressive identification of new potential diagnostic markers, the unravelling of aPL antibody-mediated pathogenic mechanisms and the development of novel therapeutic strategies. The most recent and innovative findings about aPL biologic effects and APS treatment will be hereby critically appraised.
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