Internal medicine

Eculizumab

Glomerulopathy

Complement system

Alternative complement pathway

Immunology

Paroxysmal nocturnal hemoglobinuria

Atypical hemolytic uremic syndrome

Kidney

Immune dysregulation

Glomerulonephritis

Medicine

Immune system

Seminars in Immunopathology

Atypical hemolytic uremic syndrome (aHUS), C3 glomerulopathy (C3G), and paroxysmal nocturnal hemoglobinuria (PNH) are prototypical disorders of complement dysregulation. Although complement overactivation is common to all, cell surface alternative pathway dysregulation (aHUS), fluid phase alternative pathway dysregulation (C3G), or terminal pathway dysregulation (PNH) predominates resulting in the very different phenotypes seen in these diseases. The mechanism underlying the dysregulation also varies with predominant acquired autoimmune (C3G), somatic mutations (PNH), or inherited germline mutations (aHUS) predisposing to disease. Eculizumab has revolutionized the treatment of PNH and aHUS although has been less successful in C3G. With the next generation of complement therapeutic in late stage development, these archetypal complement diseases will provide the initial targets.

Diseases of complement dysregulation—an overview