Biological therapies are used in many autoimmune diseases. Paradoxically, their use has been increasingly related with the development of a wide spectrum of autoimmune disorders. BIOGEAS nationwide registry, published in 20091 and updated in 2017,2 describes nearly 13,000 cases of autoimmune processes, such as lupus, vasculitis, sarcoidosis or thrombocytopenia. Antiphospholipid syndrome (APS) is a rare autoimmune entity. Its diagnosis is based on the Sapporo Criteria and requires the presence of clinical manifestations such as miscarriage or venous or arterial thrombosis, together with analytical criteria (antiphospolipid antibodies) on two different occasions separated by 12 weeks.3 Antiphospolipid antibodies (aPL) comprise anti-cardiolipin antibodies (aCL) IgG or IgM, anti-beta-2-glycoprotein-I antibodies (B2G) IgG or IgM and lupus anticoagulant. APS can be primary or secondary to an underlying condition like systemic lupus erythematosus. The preclinical suspicion should arise in the presence of blood coagulation test (e.g., activated partial thromboplastin time [aPTT]) prolongation on two different occasions separated by 12 weeks. First BIOGEAS registry communicated thirty-two patients who developed APS-related features after starting anti-TNF therapy. No additional cases were reported in successive updates. There are limited data about development of autoantibodies, i.e., anti-nuclear antibodies (ANA), anti-DNA or aCL in rheumatoid arthritis and psoriasis patients receiving anti-TNF treatment.4, 5, 6, 7, 8 In inflammatory bowel disease, in an article published in 1998, when the use of anti-TNF was not yet approved, patients with ulcerative colitis and Crohn's disease had a significantly higher prevalence of aCL (18.1% and 15.6%, respectively) than healthy controls (3%).9 Vermeire et al. described in a 125-participant cohort of infliximab-treated Crohn's disease patients a cumulative incidence of ANAs of 56.8% after 24 months. In this cohort, only two patients developed drug-induced lupus erythematosus.10 There is no consensus about the underlying mechanism, although a suggested hypothesis involved genetic predisposition, drug biotransformation and epigenetic dysregulation.11

After the clinical observation of aPTT prolongation in some patients of our cohort of IBD patients treated with anti-TNF, we sought to determine the presence of antiphospolipid antibodies in our population. Secondarily, we aimed to know APS incidence, primary or in the context of lupus-like syndrome in our cohort, and lastly, whether the presence of autoantibodies is associated with any other autoimmune phenomena.