Antiphospholipid antibodies are a wide and heterogeneous group of mainly IgG and/or IgM antibodies and, less frequently, IgA antibodies directed against phospholipid-protein complexes or phospholipid-binding proteins, such as P2-glycoprotein I, prothrombin, protein C, protein S, thrombomodulin, annexin V, and kininogen. The term "antiphospholipid antibody" is therefore incorrect, because the antibody is actually directed against a phospholipid-protein complex, but the name has been retained for historical reasons. Although the negatively charged phospholipid cardiolipin plays the most important role, phosphatidyl-serine, phosphatidylethanolamine, and phosphatidylcholine may also form part of the complex. The target epitope is still not fully explained [146, 147].
Lupus anticoagulants and anticardiolipin antibodies were the first such antibodies to be described. The "Sapporo" laboratory criteria for definite antiphos-pholipid syndrome require both assays to be present on two or more occasions at least six weeks apart . Lupus anticoagulant must be diagnosed according to the criteria proposed by the Subcommittee of Standardization of Lupus Anti-coagulants/Phospholipid-dependent Antibodies . Anticardiolipin antibodies must be measured using a standardized ELISA for p2-glycoprotein I-dependent antibodies; medium or high titers of IgG and/or IgM antibodies are required for a positive result. According to the Sapporo criteria, the diagnosis of definite antiphospholipid syndrome (APS) occurring as a secondary disease in SLE is established when at least one clinical criterion and one laboratory criterion are met. The clinical criteria include thrombotic events and recurrent pregnancy loss .
The prevalence of antiphospholipid antibodies in SLE varies widely; figures between 22% and 69% have been reported. This variation may be due to differences in methods or patient selection. Antiphospholipid antibodies are found less frequently in African American SLE patients. Generally, antiphospholipid antibodies appear to be more easily suppressed by treatments for active SLE . In SLE, disease activity was accompanied by significantly increased IgG-aCL, whereas no elevation was found in other diseases with detectable aCL antibodies .
Antiphospholipid syndrome is characterized by a wide spectrum of clinical manifestations that, pathophysiologically, are mainly caused by venous or arterial thrombosis, which is also associated with SLE. Dermatologic manifestations are extremely frequent in APS. The most common is livedo reticularis. Cardiac manifestations, especially valve disease, are frequently observed. Thrombocyto-penia and Coombs-positive hemolytic anemia are also often found in APS [147, 150].
A recent single-center study of 600 SLE patients showed that the prevalence of antiphospholipid antibodies was 24%; 15% had IgG aCL, 9% IgM aCL, and 15% lupus anticoagulant . A cluster of clinical events, characterized by neurologic involvement, thrombocytopenia, and IgG aCL, was observed in this study. The association of neurologic involvement with clinical or laboratory features found in APS (e.g., livedo reticularis or thrombocytopenia) was also described in previous SLE studies [152, 153]. High titers of IgG aCL were strongly associated with CNS involvement . A multivariate analysis showed that aPLs are independently associated with cerebrovascular disease, headache, and seizures in SLE. The presence of lupus anticoagulant (LAC) was independently associated with white matter hyperintensity lesions on MRI .
Catastrophic APS is an uncommon but potentially life-threatening condition that requires high clinical awareness. Thirty percent of patients with this condition have definitive SLE. The majority of patients with this condition clearly manifest microangiopathy, i.e., occlusive vascular disease that mainly affects small vessels of different organs, particularly the kidneys, lungs, brain, heart, and liver; the minority of patients experience only the typical large vessel-type occlusions seen in simple APS. The occurrence of sudden and essential aPL-in-duced coagulation or fibrinolysis disorders is highly probable in this group of patients, but precipitating factors remain unknown in most cases .
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