Objective. To analyze the clinical and immunologic manifestations of antiphospholipid syndrome (APS) in a large cohort of patients and to define patterns of disease expression.Methods. The clinical and serologic features of APS (Sapporo preliminary criteria) in 1,000 patients from 13 European countries were analyzed using a computerized database.Results. The cohort consisted of 820 female patients (82.0%) and 180 male patients (18.0%) with a mean ؎ SD age of 42 ؎ 14 years at study entry. "Primary" APS was present in 53.1% of the patients; APS was associated with systemic lupus erythematosus (SLE) in 36.2%, with lupus-like syndrome in 5.0%, and with other diseases in 5.9%. A variety of thrombotic manifestations affecting the majority of organs were recorded. A catastrophic APS occurred in 0.8% of the patients. Patients with APS associated with SLE had more episodes of arthritis and livedo reticularis, and more frequently exhibited thrombocytopenia and leukopenia. Female patients had a higher frequency of arthritis, livedo reticularis, and migraine. Male patients had a higher frequency of myocardial infarction, epilepsy, and arterial thrombosis in the lower legs and feet. In 28 patients (2.8%), disease onset occurred before age 15; these patients had more episodes of chorea and jugular vein thrombosis than the remaining patients. In 127 patients (12.7%), disease onset occurred after age 50; most of these patients were men. These patients had a

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The principle of treating-to-target has been successfully applied to many diseases outside rheumatology and more recently to rheumatoid arthritis. Identifying appropriate therapeutic targets and pursuing these systematically has led to improved care for patients with these diseases and useful guidance for healthcare providers and administrators. Thus, an initiative to evaluate possible therapeutic targets and develop treat-to-target guidance was believed to be highly appropriate in the management of systemic lupus erythematosus (SLE) patients as well. Specialists in rheumatology, nephrology, dermatology, internal medicine and clinical immunology, and a patient representative, contributed to this initiative. The majority convened on three occasions in 2012-2013. Twelve topics of critical importance were identified and a systematic literature review was performed. The results were condensed and reformulated as recommendations, discussed, modified and voted upon. The finalised bullet points were analysed for degree of agreement among the task force. The Oxford Centre level of evidence (LoE, corresponding to the research questions) and grade of recommendation (GoR) were determined for each recommendation. The 12 systematic literature searches and their summaries led to 11 recommendations. Prominent features of these recommendations are targeting remission, preventing damage and improving quality of life. LoE and GoR of the recommendations were variable but agreement was >0.9 in each case. An extensive research agenda was identified, and four overarching principles were also agreed upon. Treat-to-target-in-SLE (T2T/SLE) recommendations were developed by a large task force of multispecialty experts and a patient representative. It is anticipated that 'treating-to-target' can and will be applicable to the care of patients with SLE.

Anti

The antiphospholipid syndrome is defined by the presence of antiphospholipid antibodies in blood of patients with thrombosis or fetal loss. There is ample evidence that ␤ 2 -glycoprotein I (␤ 2 GPI) is the major antigen for antiphospholipid antibodies. The autoantibodies recognize ␤ 2 GPI when bound to anionic surfaces and not in solution. We showed that ␤ 2 GPI can exist in at least 2 different conformations: a circular plasma conformation and an "activated" open conformation. We also showed that the closed, circular conformation is maintained by interaction between the first and fifth domain of ␤ 2 GPI. By changing pH and salt concentration, we were able to convert the conformation of ␤ IntroductionThe antiphospholipid syndrome (APS) is defined as the presence of antiphospholipid antibodies in the blood of patients with thrombosis or fetal loss. The APS is one of the most common causes of acquired thrombophilia, 1 especially at younger age. In 1990, it was shown that the so-called antiphospholipid antibodies do not recognize phospholipids directly but they interact with phospholipids via the plasma protein ␤ 2 -glycoprotein I (␤ 2 GPI). [2][3][4] However, the discovery of ␤ 2 GPI as target for the autoantibodies did not provide a more in-depth knowledge on the underlying cause of the syndrome. It was unclear which metabolic pathway was disturbed by the autoantibodies because no physiologic function has convincingly been ascribed to ␤ 2 GPI to date. Nevertheless, as antibodies against ␤ 2 GPI can induce thrombosis in animal models, 5-7 the protein ␤ 2 GPI must hold an important functional clue to our understanding of the syndrome.␤ 2 GPI is a highly abundant 43-kDa protein that circulates at a concentration of approximately 200 g/mL. ␤ 2 GPI consists of 326 amino acids arranged in 5 short consensus repeat domains. 8,9 The first 4 domains contain 60 amino acids each, whereas the fifth domain has a 6-residue insertion and an additional 19-amino acid C-terminal extension. The extra amino acids are responsible for the formation of a large positively charged patch within the fifth domain of ␤ 2 GPI 10 that forms the binding site for anionic phospholipids. The anti-␤ 2 GPI antibodies that recognize an epitope located in the first domain correlate better with the thrombotic complications than antibodies directed against other domains. 11-13 Antibodies directed against ␤ 2 GPI have become one of the serologic markers characterizing the APS. 14 After binding to anionic surfaces, ␤ 2 GPI exposes a cryptic epitope that is recognized by the autoantibodies present in the APS. 11,12,15,16 These antibodies only recognize ␤ 2 GPI when it is bound to a surface and do not recognize ␤ 2 GPI in solution. Moreover, no circulating immune complexes between antibodies and ␤ 2 GPI have been detected in patient plasmas. 17 This seems not to be the result of clearance of these complexes from plasma because plasma levels of ␤ 2 GPI in antiphospholipid patients are the same as plasma levels of ␤ 2 GPI in healthy persons. 18 The crystal st...