In general, arterial thrombosis is treated with antiplatelet agents, and venous thrombosis with anticoagulant agents. with APS. This review article describes pathogenic mechanisms, clinical features, risk assessment, and management of arterial thrombosis in patients with APS. Particularly, we discuss how secondary prophylaxis may be a useful approach to reduce the occurrence of arterial thrombosis. model (22). Atherosclerosis and T cell responses mediated by aPLs have been considered as causes of arterial thrombosis. The primary trigger for arterial thrombosis is the rupture of an atherosclerotic plaque, which develops in the arterial wall through the accumulation of lipid deposits and lipid-laden macrophages (foam cells) (23). Activated platelets release the contents of granules that lead to platelet recruitment, adhesion, aggregation, and activation. The link between atherosclerosis and antigen-specific immunoreaction in patients with APS was clarified by focusing on the role of aPLs in plaque formation and abnormal arterial wall thickness (24). CD4+ T cells derived from plaques recognized b2GPI in atherothrombotic lesions. STAT2 In addition, b2GPI induced T cell proliferation and interferon (IFN) expression in plaque-derived T cell clones, suggesting that b2GPI-specific T cells exist in plaques of patients with APS. There are several findings regarding the function of b2GPI-specific T cells. b2GPI-specific T cells promote the production of monocyte matrix metalloproteinase-9 and tissue factor and perforin- or Fas/Fas ligand-mediated cytotoxicity, and could potentially assist autoantigen-specific B cells that have taken up and processed apoptotic cells (25). In a plaque, T cell responses against b2GPI, especially domain I, are associated with plaque instability that favors atherothrombosis. In addition, b2GPI binds to oxidized low-density lipoproteins (oxLDL) and likely promotes the proinflammatory and proatherogenic effects of the oxLDL molecule. The resulting oxLDL/2GPI complex becomes an immunogenic trigger for an autoimmune response (26). Patients with APS have increased serum levels of the oxLDL and 2GPI complex (27) that lead to the activation of monocytes and tissue factor expression (28). A new antigen presentation mechanism has recently been proposed that asserts misfolded proteins are transported to the cell surface in a complex with major histocompatibility complex (MHC) class II molecules and become neo-self-antigens (29). Specific human leukocyte antigen (HLA) class II alleles are associated with susceptibility to APS (30). Over 80% of patients with APS have antibodies against the complex of whole b2GPI and APS-associated HLA class II. APS is a representative disease for this concept, suggesting that the b2GPI/MHC class II complex is a major target antigen for autoantibodies in patients with APS (30, 31). Antigen presentation links the innate and adaptive immune responses. We revealed the relationship between genetic background and lymphocyte subsets in patients with APS (32). An increase in plasmablasts and a decrease in memory B cells were observed in patients with APS compared with healthy subjects, and these changes were associated with a TLR-7 Loratadine single nucleotide polymorphism (SNP). The SNP was associated with the upregulation of type I IFN-regulated genes. Furthermore, we demonstrated that CD20-negative B cells, which are composed mostly of plasmablasts, were a major source of aPLs. Clinical features of arterial thrombosis Arterial thrombosis in APS often involves coronary or cerebral arteries leading to myocardial infarction or stroke. The prevalence of arterial and venous thrombotic events in patients with APS varies in different ethnic populations (Table 1). According to a large dataset of 1 1,000 patients with APS from 13 European countries, the most common thrombotic manifestation included DVT (38.9%); however, arterial thrombosis was also common (stroke, Loratadine 19.8%; myocardial infarction, 5.5%) (33). The Loratadine Piedmont cohort from Italy reported characteristics of patients with APS, which comprised 217 patients with venous (45.6%) and arterial (35%) thrombosis (34). A single-center registration in Japan consisted of 141 patients with APS who presented the first thrombotic event in venous (32.6%) or arterial (66%) vascular territories (7). In the latter study, the most common thrombosis was cerebral infarction (61%) followed by DVT (23.4%). Recently, two population-based studies were reported from the United States (Olmsted County study) (35) and South Korea (HIRA study) (36). A total of 33 cases of APS in the Olmsted County study and 3,088 cases in the HIRA study were identified. In the Olmsted County study, DVT was the most frequent manifestation that occurred in 42% of the cases,.