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Journal Article
Research Support, Non-U.S. Gov't
Review
The Role of Complement in Autoimmune Disease-Associated Thrombotic Microangiopathy and the Potential for Therapeutics.
Journal of Rheumatology 2023 June
The complement system is a tightly regulated, cascading protein network representing a key component linking the innate and humoral immune systems. However, if misdirected or dysregulated, it can be similarly damaging to host-tissue. The role of complement dysregulation on vascular endothelial cells has been well established in atypical hemolytic uremic syndrome (aHUS), a thrombotic microangiopathy (TMA) characterized by microangiopathic hemolytic anemia, thrombocytopenia, and target organ injury. Yet, a great deal of complexity exists around the role of complement in TMA associated with other diseases. A further complicating factor is the cross-talk between complement, neutrophils, and coagulation pathways in the pathophysiology of TMA. Advancements in the understanding of the etiopathogenesis of aHUS paved the way for the successful development of anticomplement therapies (complement C5 inhibitors), which have revolutionized the treatment of aHUS. Therefore, a clearer understanding of the role of the complement system in TMA associated with other conditions will help to identify patients who would benefit from these therapies. This review aims to provide an assessment of the nature and extent of complement involvement in TMA associated with autoimmune diseases such as systemic lupus erythematosus, antiphospholipid syndrome, and scleroderma renal crisis. Defining the role of complement in TMA in these conditions will help to guide timely diagnosis and management.
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