Factor H (FH) is a critical regulatory protein in the complement system, primarily responsible for controlling the alternative pathway to prevent excessive immune activation. It inhibits complement activation by binding to host cells and pathogens, protecting healthy tissues from unintended damage. Dysregulation of FH is linked to several diseases, including atypical hemolytic uremic syndrome (aHUS), C3 glomerulopathy, and age-related macular degeneration (AMD).
FH autoantibodies, detected in some patients, disrupt this regulatory function. In aHUS, ~10% of cases involve anti-FH antibodies that impair FH’s ability to bind host cells, leading to uncontrolled complement activation, endothelial injury, and thrombotic microangiopathy. These antibodies are often associated with genetic mutations in FH or complement factors. Detection methods like ELISA or Western blot aid in diagnosis, particularly in pediatric aHUS cases.
Research highlights the role of anti-FH antibodies in driving complement-mediated tissue damage, prompting therapies targeting antibody removal (e.g., plasma exchange) or complement inhibition (e.g., anti-C5 monoclonal antibodies). Ongoing studies explore the interplay between genetic susceptibility, antibody production, and disease progression, aiming to refine diagnostic and therapeutic strategies. Understanding FH antibodies remains vital for managing complement-related disorders and improving patient outcomes.