title: A human monoclonal antibody against the collagen type IV α3NC1 domain is a non-invasive optical biomarker for glomerular diseases.
abstract: Progressive kidney disease is a significant clinical problem. However, despite research aimed toward developing improved predictors of disease, the major tool to assess kidney ultrastructure damage is the kidney biopsy. Here we tested the capability of a labeled human monoclonal antibody (F1.1), directed against the NC1 domain of α3(IV) collagen, to detect pathologic kidney alterations in vivo using mouse models of nephrotoxic serum-induced nephritis and puromycin aminoglycoside nephrosis. The F1.1 antibody-fluorophore conjugate signal rapidly localized specifically to injured glomeruli in both the severe and mild kidney disease models while minimally labeling healthy kidney. This differential labeling is likely due to cryptic NC1-domain exposure as enzymatic or chemical treatment of healthy human or mouse kidney sections significantly increased F1.1 binding to the glomeruli. Finally, kidney tissue from patients with renal disease show significant glomerular staining by F1.1 indicating that exposure of the NC1 domain occurs in clinically relevant circumstances. Thus, NC1 domain exposure may represent an in situ biomarker for assessment of kidney injury. Our study suggests that F1.1 and similar antibodies may represent a new class of non-invasive renal imaging reagents.
authors.affiliation: Cancer Immunology, Inflammation, and Tolerance Program, Cancer Center, Georgia Health Sciences University, Augusta, Georgia 30912, USA.
authors.forename: Kapil
authors.initials: K
authors.lastname: Chaudhary
authors.forename: Daniel T
authors.initials: DT
authors.lastname: Kleven
authors.forename: Tracy L
authors.initials: TL
authors.lastname: McGaha
authors.forename: Michael P
authors.initials: MP
authors.lastname: Madaio
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D000911:Antibodies, Monoclonal; D001324:Autoantigens / Q000032:analysis* / Q000276:immunology; D015415:Biomarkers / Q000032:analysis; D002648:Child; D024141:Collagen Type IV / Q000032:analysis* / Q000276:immunology; D004195:Disease Models, Animal; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007678:Kidney Glomerulus / Q000737:chemistry* / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008875:Middle Aged; D009393:Nephritis / Q000139:chemically induced / Q000175:diagnosis* / Q000276:immunology / Q000378:metabolism; D009401:Nephrosis / Q000139:chemically induced / Q000175:diagnosis* / Q000276:immunology / Q000378:metabolism; D011237:Predictive Value of Tests; D017434:Protein Structure, Tertiary; D011691:Puromycin; D012720:Severity of Illness Index; D013997:Time Factors; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D001324:Autoantigens; D015415:Biomarkers; D024141:Collagen Type IV; C057112:type IV collagen alpha3 chain; D011691:Puromycin