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Detection of complement activation using monoclonal antibodies against C3d

Department of Medicine


Faculty and Post-Docs within the Department of Medicine regularly study and publish groundbreaking research. We are excited to highlight published research papers.

This paper's research on complement activation was conducted primarily by Joshua Thurman, Associate Professor in the Department of Medicine Division of Renal Disease and Hypertension, V. Michael Holers, Professor and Division Head in the Department of Medicine Division of Rheumatology, and Liudmila Kulik, Instructor in the Department of Medicine Division of Rheumatology. Jonathan Hannan, in the Division of Rheumatology, also collaborated on these studies.

Abstract: During complement activation the C3 protein is cleaved, and C3 activation fragments are covalently fixed to tissues. Tissue-bound C3 fragments are a durable biomarker of tissue inflammation, and these fragments have been exploited as addressable binding ligands for targeted therapeutics and diagnostic agents. We have generated cross-reactive murine monoclonal antibodies against human and mouse C3d, the final C3 degradation fragment generated during complement activation. We developed 3 monoclonal antibodies (3d8b, 3d9a, and 3d29) that preferentially bind to the iC3b, C3dg, and C3d fragments in solution, but do not bind to intact C3 or C3b. The same 3 clones also bind to tissue-bound C3 activation fragments when injected systemically. Using mouse models of renal and ocular disease, we confirmed that, following systemic injection, the antibodies accumulated at sites of C3 fragment deposition within the glomerulus, the renal tubulointerstitium, and the posterior pole of the eye. To detect antibodies bound within the eye, we used optical imaging and observed accumulation of the antibodies within retinal lesions in a model of choroidal neovascularization (CNV). Our results demonstrate that imaging methods that use these antibodies may provide a sensitive means of detecting and monitoring complement activation–associated tissue inflammation.