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Proteomic Analysis of Complement Proteins in Membranous Nephropathy
- Source :
- Kidney International Reports, Vol 5, Iss 5, Pp 618-626 (2020)
- Publication Year :
- 2020
- Publisher :
- Elsevier, 2020.
-
Abstract
- Introduction: Membranous nephropathy (MN) is the most common cause of nephrotic syndrome in Caucasian adults. Phospholipase A2 receptor (PLA2R)– and exostosin 1 (EXT1)/exostosin 2 (EXT2)–associated MN represent the most common primary and secondary forms of MN. The complement profile using a proteomics approach has not been studied in these 2 common forms of MN. Methods: We used laser microdissection and mass spectrometry (MS/MS) to dissect glomeruli and identify glomerular complement proteins in PLA2R-associated (n = 7), EXT1/EXT2-associated MN (n = 21), and 11 control cases (time 0 transplant biopsies). Results: MS/MS identified high total spectral counts for PLA2R and EXT1/EXT2 in corresponding cases of PLA2R- and EXT1/EXT2-positive MN. Both PLA2R- and EXT1/EXT2-associated MN had high spectral counts of complement proteins C3, C4, C5, C6, C7, C8, and C9. Complement protein C1 was present in low spectral counts in EXT1/EXT2-associated MN. Regulators of complement activation that were detected in MN included higher spectral counts of FH, FHR-1, FHR-5, clusterin, vitronectin and lower spectral counts of FHR-3, FHR-4, and CD59. Low spectral counts of FB and properdin, key components of the alternative pathway, also were detected. IgG4 and IgG1 were the most abundant IgG subclasses in PLA2R- and EXT1/EXT2-associated MN. Lower spectral counts for C3, C4, and C5 were detected in control cases when compared with MN. Conclusion: Significant complement activation is present in MN as evidenced by large spectral counts of complement proteins from C3- and C4-based pathways, including regulatory proteins of complement pathways. These data suggest that anticomplement drugs may be effective in treatment for MN. Keywords: complement, laser microdissection, mass spectrometry, membranous nephropathy
- Subjects :
- Clusterin
biology
business.industry
030232 urology & nephrology
CD59
030204 cardiovascular system & hematology
medicine.disease
Proteomics
lcsh:Diseases of the genitourinary system. Urology
lcsh:RC870-923
Molecular biology
Complement system
03 medical and health sciences
0302 clinical medicine
Membranous nephropathy
Nephrology
medicine
biology.protein
Alternative complement pathway
Properdin
Vitronectin
business
Subjects
Details
- Language :
- English
- ISSN :
- 24680249
- Volume :
- 5
- Issue :
- 5
- Database :
- OpenAIRE
- Journal :
- Kidney International Reports
- Accession number :
- edsair.doi.dedup.....6c746cb3898c002e7551c311160ce5aa