Oxidative stress and galactose-deficient IgA1 as markers of progression in IgA nephropathy

Roberta Camilla, Hitoshi Suzuki, Valentina Daprà, Elisa Loiacono, Licia Peruzzi, Alessandro Amore, Gian Marco Ghiggeri, Gianna Mazzucco, Francesco Scolari, Ali G. Gharavi, Gerald B. Appel, Stéphan Troyanov, Jan Novak, Bruce A. Julian, Rosanna Coppo

Research output: Contribution to journalArticle

65 Citations (Scopus)

Abstract

Background and objectives We assessed the activation of the oxidative stress pathway in patients with IgA nephropathy (IgAN), while evaluating the classic marker of the disease (galactose-deficient serum IgA1). Design, setting, participants, & measurements Sera from 292 patients and 69 healthy controls from Italy and the United States were assayed for advanced oxidation protein products (AOPPs), free sulfhydryl groups on albumin (SH-Alb), and IgA1 with galactose-deficient hinge-region O-glycans (Gd-IgA1). Gd-IgA1 was detected by binding to Helix aspersa agglutinin (HAA) and expressed as total Gd-IgA1 or as degree of galactose deficiency relative to a standard Gd-IgA1 myeloma protein (%HAA). Results Sera from IgAN patients showed higher levels of Gd-IgA1, %HAA, and AOPPs, but lower levels of SH-Alb in comparison to that from healthy controls. Serum levels of AOPPs significantly correlated with serum Gd-IgA1 and %HAA. The relationship between these biomarkers and clinical features at sampling and during follow-up was assessed in 62 patients with long-term follow-up. AOPPs and %HAA correlated with proteinuria at sampling and independently associated with subsequent proteinuria. Levels of AOPPs correlated with rate of decline in renal function after sampling. The combination of a high level of AOPPs and a high level of %HAA associated with decline in estimated GFR. Conclusions Serum levels of aberrantly glycosylated IgA1 are elevated and oxidative stress pathways are activated in patients with IgAN; the intensity of the stress correlated with expression and progression of the disease. We speculate that oxidative stress may modulate the nephrotoxicity of aberrantly glycosylated IgA1 in IgAN.

Original languageEnglish
Pages (from-to)1903-1911
Number of pages9
JournalClinical Journal of the American Society of Nephrology
Volume6
Issue number8
DOIs
Publication statusPublished - Aug 1 2011

Fingerprint

Galactose
Immunoglobulin A
Oxidative Stress
Advanced Oxidation Protein Products
Agglutinins
Serum
Proteinuria
Myeloma Proteins
Italy
Polysaccharides
Disease Progression
Albumins
Biomarkers

ASJC Scopus subject areas

  • Nephrology
  • Transplantation
  • Epidemiology
  • Critical Care and Intensive Care Medicine

Cite this

Oxidative stress and galactose-deficient IgA1 as markers of progression in IgA nephropathy. / Camilla, Roberta; Suzuki, Hitoshi; Daprà, Valentina; Loiacono, Elisa; Peruzzi, Licia; Amore, Alessandro; Ghiggeri, Gian Marco; Mazzucco, Gianna; Scolari, Francesco; Gharavi, Ali G.; Appel, Gerald B.; Troyanov, Stéphan; Novak, Jan; Julian, Bruce A.; Coppo, Rosanna.

In: Clinical Journal of the American Society of Nephrology, Vol. 6, No. 8, 01.08.2011, p. 1903-1911.

Research output: Contribution to journalArticle

Camilla, R, Suzuki, H, Daprà, V, Loiacono, E, Peruzzi, L, Amore, A, Ghiggeri, GM, Mazzucco, G, Scolari, F, Gharavi, AG, Appel, GB, Troyanov, S, Novak, J, Julian, BA & Coppo, R 2011, 'Oxidative stress and galactose-deficient IgA1 as markers of progression in IgA nephropathy', Clinical Journal of the American Society of Nephrology, vol. 6, no. 8, pp. 1903-1911. https://doi.org/10.2215/CJN.11571210
Camilla, Roberta ; Suzuki, Hitoshi ; Daprà, Valentina ; Loiacono, Elisa ; Peruzzi, Licia ; Amore, Alessandro ; Ghiggeri, Gian Marco ; Mazzucco, Gianna ; Scolari, Francesco ; Gharavi, Ali G. ; Appel, Gerald B. ; Troyanov, Stéphan ; Novak, Jan ; Julian, Bruce A. ; Coppo, Rosanna. / Oxidative stress and galactose-deficient IgA1 as markers of progression in IgA nephropathy. In: Clinical Journal of the American Society of Nephrology. 2011 ; Vol. 6, No. 8. pp. 1903-1911.
@article{c247c63f754446cba71d8a6762b690ff,
title = "Oxidative stress and galactose-deficient IgA1 as markers of progression in IgA nephropathy",
abstract = "Background and objectives We assessed the activation of the oxidative stress pathway in patients with IgA nephropathy (IgAN), while evaluating the classic marker of the disease (galactose-deficient serum IgA1). Design, setting, participants, & measurements Sera from 292 patients and 69 healthy controls from Italy and the United States were assayed for advanced oxidation protein products (AOPPs), free sulfhydryl groups on albumin (SH-Alb), and IgA1 with galactose-deficient hinge-region O-glycans (Gd-IgA1). Gd-IgA1 was detected by binding to Helix aspersa agglutinin (HAA) and expressed as total Gd-IgA1 or as degree of galactose deficiency relative to a standard Gd-IgA1 myeloma protein ({\%}HAA). Results Sera from IgAN patients showed higher levels of Gd-IgA1, {\%}HAA, and AOPPs, but lower levels of SH-Alb in comparison to that from healthy controls. Serum levels of AOPPs significantly correlated with serum Gd-IgA1 and {\%}HAA. The relationship between these biomarkers and clinical features at sampling and during follow-up was assessed in 62 patients with long-term follow-up. AOPPs and {\%}HAA correlated with proteinuria at sampling and independently associated with subsequent proteinuria. Levels of AOPPs correlated with rate of decline in renal function after sampling. The combination of a high level of AOPPs and a high level of {\%}HAA associated with decline in estimated GFR. Conclusions Serum levels of aberrantly glycosylated IgA1 are elevated and oxidative stress pathways are activated in patients with IgAN; the intensity of the stress correlated with expression and progression of the disease. We speculate that oxidative stress may modulate the nephrotoxicity of aberrantly glycosylated IgA1 in IgAN.",
author = "Roberta Camilla and Hitoshi Suzuki and Valentina Dapr{\`a} and Elisa Loiacono and Licia Peruzzi and Alessandro Amore and Ghiggeri, {Gian Marco} and Gianna Mazzucco and Francesco Scolari and Gharavi, {Ali G.} and Appel, {Gerald B.} and St{\'e}phan Troyanov and Jan Novak and Julian, {Bruce A.} and Rosanna Coppo",
year = "2011",
month = "8",
day = "1",
doi = "10.2215/CJN.11571210",
language = "English",
volume = "6",
pages = "1903--1911",
journal = "Clinical journal of the American Society of Nephrology : CJASN",
issn = "1555-9041",
publisher = "by the American Society of Nephrology",
number = "8",

}

TY - JOUR

T1 - Oxidative stress and galactose-deficient IgA1 as markers of progression in IgA nephropathy

AU - Camilla, Roberta

AU - Suzuki, Hitoshi

AU - Daprà, Valentina

AU - Loiacono, Elisa

AU - Peruzzi, Licia

AU - Amore, Alessandro

AU - Ghiggeri, Gian Marco

AU - Mazzucco, Gianna

AU - Scolari, Francesco

AU - Gharavi, Ali G.

AU - Appel, Gerald B.

AU - Troyanov, Stéphan

AU - Novak, Jan

AU - Julian, Bruce A.

AU - Coppo, Rosanna

PY - 2011/8/1

Y1 - 2011/8/1

N2 - Background and objectives We assessed the activation of the oxidative stress pathway in patients with IgA nephropathy (IgAN), while evaluating the classic marker of the disease (galactose-deficient serum IgA1). Design, setting, participants, & measurements Sera from 292 patients and 69 healthy controls from Italy and the United States were assayed for advanced oxidation protein products (AOPPs), free sulfhydryl groups on albumin (SH-Alb), and IgA1 with galactose-deficient hinge-region O-glycans (Gd-IgA1). Gd-IgA1 was detected by binding to Helix aspersa agglutinin (HAA) and expressed as total Gd-IgA1 or as degree of galactose deficiency relative to a standard Gd-IgA1 myeloma protein (%HAA). Results Sera from IgAN patients showed higher levels of Gd-IgA1, %HAA, and AOPPs, but lower levels of SH-Alb in comparison to that from healthy controls. Serum levels of AOPPs significantly correlated with serum Gd-IgA1 and %HAA. The relationship between these biomarkers and clinical features at sampling and during follow-up was assessed in 62 patients with long-term follow-up. AOPPs and %HAA correlated with proteinuria at sampling and independently associated with subsequent proteinuria. Levels of AOPPs correlated with rate of decline in renal function after sampling. The combination of a high level of AOPPs and a high level of %HAA associated with decline in estimated GFR. Conclusions Serum levels of aberrantly glycosylated IgA1 are elevated and oxidative stress pathways are activated in patients with IgAN; the intensity of the stress correlated with expression and progression of the disease. We speculate that oxidative stress may modulate the nephrotoxicity of aberrantly glycosylated IgA1 in IgAN.

AB - Background and objectives We assessed the activation of the oxidative stress pathway in patients with IgA nephropathy (IgAN), while evaluating the classic marker of the disease (galactose-deficient serum IgA1). Design, setting, participants, & measurements Sera from 292 patients and 69 healthy controls from Italy and the United States were assayed for advanced oxidation protein products (AOPPs), free sulfhydryl groups on albumin (SH-Alb), and IgA1 with galactose-deficient hinge-region O-glycans (Gd-IgA1). Gd-IgA1 was detected by binding to Helix aspersa agglutinin (HAA) and expressed as total Gd-IgA1 or as degree of galactose deficiency relative to a standard Gd-IgA1 myeloma protein (%HAA). Results Sera from IgAN patients showed higher levels of Gd-IgA1, %HAA, and AOPPs, but lower levels of SH-Alb in comparison to that from healthy controls. Serum levels of AOPPs significantly correlated with serum Gd-IgA1 and %HAA. The relationship between these biomarkers and clinical features at sampling and during follow-up was assessed in 62 patients with long-term follow-up. AOPPs and %HAA correlated with proteinuria at sampling and independently associated with subsequent proteinuria. Levels of AOPPs correlated with rate of decline in renal function after sampling. The combination of a high level of AOPPs and a high level of %HAA associated with decline in estimated GFR. Conclusions Serum levels of aberrantly glycosylated IgA1 are elevated and oxidative stress pathways are activated in patients with IgAN; the intensity of the stress correlated with expression and progression of the disease. We speculate that oxidative stress may modulate the nephrotoxicity of aberrantly glycosylated IgA1 in IgAN.

UR - http://www.scopus.com/inward/record.url?scp=80051575524&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80051575524&partnerID=8YFLogxK

U2 - 10.2215/CJN.11571210

DO - 10.2215/CJN.11571210

M3 - Article

C2 - 21784819

AN - SCOPUS:80051575524

VL - 6

SP - 1903

EP - 1911

JO - Clinical journal of the American Society of Nephrology : CJASN

JF - Clinical journal of the American Society of Nephrology : CJASN

SN - 1555-9041

IS - 8

ER -