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JOURNAL ARTICLE
RESEARCH SUPPORT, N.I.H., EXTRAMURAL
RESEARCH SUPPORT, NON-U.S. GOV'T
REVIEW
All Things Complement.
The complement (C) cascade is an ancient system of proteins whose primary role is to initiate and modulate immune responses. During C activation, circulating proteins are cleaved and nascent cleavage fragments participate in a broad range of downstream innate and adaptive immune functions. Although the majority of these functions are either homeostatic or protective, a large body of experimental and clinical evidence also highlights a central role for the C system in the pathogenesis of many types of glomerular disease. From classic pathway activation in lupus nephritis to alternative pathway dysregulation in C3 glomerulopathy, our understanding of the spectrum of C involvement in kidney disease has expanded greatly in recent years. However, the characteristics that make the glomerulus so uniquely susceptible to C-mediated injury are not fully understood, and this remains an area of ongoing investigation. Several C inhibitors have been approved for clinical use, and additional C inhibitory drugs are in development. The use of these drugs in patients with kidney disease will expand our understanding of the benefits and limitations of C inhibition.
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