Complement and autoimmune glomerular diseases.
The renal glomerulus is the specialized structure in the kidney responsible for generating over 150 liters of plasma ultrafiltrate per day in humans. Certain characteristics of this structure favor involvement in autoimmune diseases. Formation of immune complexes in the glomerulus, either deposited from the circulation or generated in situ, can activate the complement system. Active products of this system include the anaphylatoxins C3a and C5a, C3b, which covalently associates with immune complexes, and the C5b-9 membrane attack complex. If complement is activated in a site accessible to blood constituents, such as in the subendothelial and mesangial regions, generated C3a, C5a and C3b can interact with their respective receptors on inflammatory cells to lead to an exudative lesion. In addition, intrinsic glomerular cells bearing relevant receptors may also be activated and can proliferate to contribute to the inflammation. In a privileged site such as the subepithelial region, complement activation products are not accessible to blood cells, and as such, the resultant pathology is noninflammatory. In this setting, effects of C5b-9 predominate, which include activation and injury of cells through still incompletely characterized pathways. Various means to alter the complement pathway are now available, including antibody inhibitors and recombinant proteins based upon naturally occurring complement regulators. The use of these agents, as well as mice in which individual components of the complement system have been deleted, has given a great deal of insight into how the complement system is involved in glomerular disease. The ability to manipulate the complement pathway is now a reality in a clinical setting, yet conclusive human studies are difficult to achieve.
Quigg
Richard J
RJ
University of Chicago, Section of Nephrology, Chicago, Ill., USA. rquigg@medicine.uchicago.edu
D000818:Animals; D000936:Antigen-Antibody Complex / Q000378:metabolism; D001327:Autoimmune Diseases / Q000209:etiology* / Q000276:immunology; D003169:Complement Inactivator Proteins / Q000627:therapeutic use; D003165:Complement System Proteins / Q000502:physiology*; D006801:Humans; D007674:Kidney Diseases / Q000209:etiology* / Q000276:immunology; D007678:Kidney Glomerulus / Q000473:pathology*; D008181:Lupus Nephritis / Q000209:etiology
D000936:Antigen-Antibody Complex; D003169:Complement Inactivator Proteins; D003165:Complement System Proteins