Role of Complement in Glomerular injury


Consultant Nephrologist,
Medical Director, Nephrology Department 417 Army Share Fund Hospital, Athens, Greece
Professor-Consultant Hellenic Open University

A complement-oriented approach has allowed renal physicians community to  come increasingly close to answering the question why a glomerulopephritis is happening regardless the  traditional dichotomous classification scheme  (primary vs secondary) and to provide a guide to prognosis and treatment of a number of glomerular diseases. The complement system is divided into 3 initiating pathways—the classical, lectin, and alternative pathways.  Although all 3 pathways converge at a similar level and therefore have similar downstream targets, the pathways are distinct in their points of origin.  This distinction  is clearly demostarting in immunofluorescence  (IF) studies after kidney biopsies, with the example of lupus nephritis, C3 nephropathy, membranous nephropathy to be some of the most pronounced ones.  The classic pattern of Lupus Nephritis  is an immune complex–mediated glomerulonephritis  with a varied pathology that includes 6 distinct classes of disease and  a so-called full house pattern in IF.  M-type phospholipase A2 receptor (PLA2R) is  the specific podocyte antigen responsible for eliciting immune complex formation with circulating autoantibodies in membranous nephropathy.  Anti-PLA2R antibodies are detected in approximately 75% of idiopathic membranous cases  and permeate the Glomerular Basement Membrane.   C3 glomerulopathy has glomerular pathology associated with deposition of complement C3 in the absence of immunoglobulins. The term  C3 glomerulopathy should be used to designate a disease process due to abnormal control of complement activation, deposition or degradation.  C3 glomerulopathies overlap with atypical hemolytic uremic syndrome.  Moreover, this approach to pathogenesis inevitably spurs discussions of treatment directed at the complement system.  The complement system is a double edge sword: promote homeostasis and protection and at the same time can lead to tissue injury.