Unraveling pathogenic mechanisms of antiphospholipid syndrome

Abstract

Antiphospholipid syndrome (APS) is an autoimmune disease characterized by the presence of antiphospholipid antibodies (aPL) and APS patients often experience thrombotic and/or obstetric complications. Patients are prescribed anticoagulant medication, but effective treatment is lacking. Unraveling the pathophysiology of APS could contribute to finding new treatment options. The aim of this thesis is to elucidate the pathophysiology of APS. It focuses on two questions related to the pathology of APS, the origin of aPL and the causal relationship between aPL and thrombotic events.

To study the origin of autoimmunity in APS, we focused on the intestinal microbiome. We investigated the composition of the intestinal microbiome and mechanisms causing autoimmunity in APS patients. The intestinal microbiome could play a role in the origin of autoimmunity in APS, not through altered composition but potentially through cross-immunization, with the Roseburia genus as major lead.

To identify the origin of thrombosis in APS pathogenesis, we focused on the intrinsic pathway of the coagulation cascade and the plasma protein profile. The origin of thrombosis is not found in increased intrinsic pathway activation in stable APS patients, but six proteins involved in subclinical inflammation and renal involvement provide new leads for APS pathogenesis.