Apolipoprotein E is enriched in dense deposits and is a marker for dense deposit disease in C3 glomerulopathy.

Autor:	Madden B; Mayo Clinic Proteomics Core, Mayo Clinic, Rochester, Minnesota, USA., Singh RD; Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota, USA., Haas M; Department of Pathology & Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA., Palma LMP; Pediatric Nephrology, State University of Campinas (UNICAMP), Campinas, Brazil., Sharma A; Department of Renal Pathology & Electron Microscopy, Dr Lal Path Labs, New Delhi, India., Vargas MJ; Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota, USA., Gross L; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA., Negron V; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA., Nate T; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA., Charlesworth MC; Mayo Clinic Proteomics Core, Mayo Clinic, Rochester, Minnesota, USA., Theis JD; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA., Nasr SH; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA., Nath KA; Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota, USA., Fervenza FC; Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota, USA., Sethi S; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA. Electronic address: sethi.sanjeev@mayo.edu.
Jazyk:	angličtina
Zdroj:	Kidney international [Kidney Int] 2024 May; Vol. 105 (5), pp. 1077-1087. Date of Electronic Publication: 2024 Mar 04.
DOI:	10.1016/j.kint.2024.02.013
Abstrakt:	C3 glomerulopathy (C3G) is a rare disease resulting from dysregulation of the alternative pathway of complement. C3G includes C3 glomerulonephritis (C3GN) and dense deposit disease (DDD), both of which are characterized by bright glomerular C3 staining on immunofluorescence studies. However, on electron microscopy (EM), DDD is characterized by dense osmiophilic mesangial and intramembranous deposits along the glomerular basement membranes (GBM), while the deposits of C3GN are not dense. Why the deposits appear dense in DDD and not in C3GN is not known. We performed laser microdissection (LCM) of glomeruli followed by mass spectrometry (MS) in 12 cases each of DDD, C3GN, and pretransplant kidney control biopsies. LCM/MS showed marked accumulation of complement proteins C3, C5, C6, C7, C8, C9 and complement regulating proteins CFHR5, CFHR1, and CFH in C3GN and DDD compared to controls. C3, CFH and CFHR proteins were comparable in C3GN and DDD. Yet, there were significant differences. First, there was a six-to-nine-fold increase of C5-9 in DDD compared to C3GN. Secondly, an unexpected finding was a nine-fold increase in apolipoprotein E (ApoE) in DDD compared to C3GN. Most importantly, immunohistochemical and confocal staining for ApoE mirrored the dense deposit staining in the GBM in DDD but not in C3GN or control cases. Validation studies using 31 C3G cases confirmed the diagnosis of C3GN and DDD in 80.6 % based on ApoE staining. Overall, there is a higher burden of terminal complement pathway proteins in DDD compared to C3GN. Thus, our study shows that dense deposits in DDD are enriched with ApoE compared to C3GN and control cases. Hence, ApoE staining may be used as an adjunct to EM for the diagnosis of DDD and might be valuable when EM is not available. (Copyright © 2024 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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