The Role of Complement in the Pathogenesis of HUS and the TMA Spectrum Disorders

Abstract

This review aims to examine the current definitions of primary and secondary hemolytic uremic syndromes. Specifically, it seeks to determine which external conditions can result in secondary Thrombotic microangiopathy (TMA), which can trigger cases of primary atypical uremic syndromes (aHUS), and the role of complement in the pathogenesis of TMA spectrum disorders. Building on the growing insight about the pathogenic role of dysregulation of the alternative complement pathway in primary aHUS, the successful use of complement-blocking treatment in cases of thrombotic microangiopathy with coexisting conditions (secondary TMA), along with the identification of complement mutations in some of these cases, indicates a so far possibly under-appreciated pathogenic role for complement in diagnoses within the TMA spectrum. Uncontrolled complement activity and pro-thrombotic environments represent a unifying pathogenic mechanism in aHUS and the TMA spectrum disorders and point towards shared diagnostic and therapeutic pathways.