Hematology Disease Topics & Pathways:
Research, Fundamental Science, Translational Research, Clinical Practice (Health Services and Quality), Clinical Research, Diseases, Immune Disorders, Infectious Diseases, Therapies
The Complement System and Medicine: The Good, the Bad, the Future
Overactivation of the complement system contributes to the pathophysiology of many diseases including systemic lupus erythematosus, glomerulonephritis, arthritis, reperfusion cardiac injury, macular degeneration, atypical hemolytic uremic syndrome (aHUS), and hereditary angioedema, among others.
Deficiencies of the complement system are implicated in autoimmune conditions and in a predisposition to infection, particularly by Neisseria meningitides. Paroxysmal nocturnal hemoglobinuria (PNH) is the archetypal complement-dependent disease in which most of the symptoms and complications are due to the loss of two specific complement inhibitors, decay accelerating factor (DAF/CD55) and membrane inhibitor of reactive lysis (MIRL/CD59), from the membranes of hematopoietic cells. Twenty years ago, the first successful trial of anti-complement therapy was performed in PNH subsequently leading in 2007 to the FDA approval of eculizumab, a C5 inhibitor. This not only presented a dramatic change in the management of PNH but also paved the way for the approval of eculizumab in other diseases including aHUS, myasthenia gravis and neuromyelitis optica spectrum disorder. In addition, this early experience heralded the development of other complement inhibitors in many other diseases.
John Atkinson, MD, of the Washington University School of Medicine in St. Louis, will provide an update on the status of the three complement activation pathways and their regulators and receptors. The pathophysiologic basis of multiple diseases in which the hematologist, nephrologist, dermatologist, and rheumatologist often come together will be highlighted along with a focus on therapeutic agents, already approved or hoping soon to be in the marketplace.
Peter Hillmen, MD, PhD, of University of Leeds School of Medicine, will describe the development of anti-complement therapy and the recent developments in complement inhibition in PNH. He will give insights into the recent development of alternative complement inhibitors and their potential roles across medicine.