Urinary complement profile in IgA nephropathy and its correlation with the clinical and pathological characteristics

Dongqing Wang; Changwei Wu; Sipei Chen; Yi Li; Li Wang; Yong Zhang; Guisen Li

doi:10.3389/fimmu.2023.1117995

Urinary complement profile in IgA nephropathy and its correlation with the clinical and pathological characteristics

Front Immunol. 2023 Mar 20:14:1117995. doi: 10.3389/fimmu.2023.1117995. eCollection 2023.

Authors

Dongqing Wang¹, Changwei Wu¹, Sipei Chen¹, Yi Li¹, Li Wang¹, Yong Zhang², Guisen Li¹

Affiliations

¹ Renal Department and Nephrology Institute, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
² Institutes for Systems Genetics, West China Hospital, Sichuan University, Chengdu, China.

Abstract

Background and objectives: The activated complement profile in IgA nephropathy (IgAN) is still unclear. Our study investigated the profile of urinary complements in IgAN patients and its correlations with clinical and pathological characteristics.

Methods: Urinary protein abundance was detected by liquid chromatography-tandem mass spectrometry (LC-MS/MS) in 50 IgAN, 50 membranous nephropathy (MN), and 68 healthy controls (HC). Then, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to identify differentially expressed proteins in IgAN patients. The differentially expressed complement proteins were screened in IgAN patients, and their correlations with laboratory or pathological parameters were analyzed. Thereafter, 7 complement components were validated by enzyme-linked immunosorbent assay (ELISA) in the urine samples of 45 IgAN patients.

Results: There were 786 differentially expressed proteins between IgAN and HC. KEGG analysis showed that differentially expressed urinary proteins in IgAN were enriched with complement. Of these, 67% of urinary complement protein abundance was associated with the estimated glomerular filtration rate. The urinary complement-related protein collectin12 (colec12), complement H factor (CFH), complement H factor-related protein 2 (CFHR2), and complement B factor (CFB) were positively correlated with serum creatinine; colec12, CFHR2, CFB, and C8g were positively correlated with glomerulosclerosis; CFH, CFHR2, C8g, and C9 were positively correlated with tubular atrophy/interstitial fibrosis.

Conclusion: Abnormally increased components of complement pathways significantly correlate with reduced renal function, proteinuria, and renal histological damage in IgAN. It could provide a potential biomarker panel for monitoring IgAN and provide clues for therapeutic choice targeting complement system of IgAN patients.

Keywords: IgA nephropathy; complement; histopathology; proteinuria; proteomics.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Chromatography, Liquid
Complement Factor H / analysis
Complement System Proteins / analysis
Glomerulonephritis, IGA* / pathology
Humans
Kidney / pathology
Tandem Mass Spectrometry

Substances

Complement System Proteins
Complement Factor H

Grants and funding

This work was supported by the National Natural Science Foundation of China (82070690, U21A20349, 31901038).