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Multi-Autoantibody Signature and Clinical Outcome in Membranous Nephropathy.
- Source :
-
Clinical journal of the American Society of Nephrology : CJASN [Clin J Am Soc Nephrol] 2020 Dec 07; Vol. 15 (12), pp. 1762-1776. Date of Electronic Publication: 2020 Nov 30. - Publication Year :
- 2020
-
Abstract
- Background and Objectives: Patients with membranous nephropathy can have circulating autoantibodies against membrane-bound (phospholipase A2 receptor 1 [PLA2R1] and thrombospondin type-1 domain containing 7A [THSD7A]) and intracellular (aldose reductase, SOD2, and α-enolase) podocyte autoantigens. We studied their combined association with clinical outcomes.<br />Design, Setting, Participants, & Measurements: Serum levels of anti-PLA2R1, anti-THSD7A, anti-aldose reductase, anti-SOD2, and anti-α-enolase autoantibodies were determined in 285 patients at diagnosis and during follow-up using standardized and homemade assays. An eGFR>60 ml/min per 1.73 m <superscript>2</superscript> and remission of proteinuria (<0.3/<3.5 g per d) after 12 months were the outcomes of interest.<br />Results: At diagnosis, 182 (64%), eight (3%), and 95 (33%) patients were anti-PLA2R1 <superscript>+</superscript> , anti-THSD7A <superscript>+</superscript> , and double negative, respectively. The prevalence of a detectable antibody to at least one intracellular antigen was similarly distributed in patients who were anti-PLA2R1 <superscript>+</superscript> ( n =118, 65%) and double negative ( n =64, 67%). Positivity for anti-PLA2R1, anti-SOD2, and anti-α-enolase antibodies and higher titers at diagnosis were associated with poor clinical outcome independently to each other. Combined positivity for anti-PLA2R1, anti-SOD2, and anti-α-enolase was associated with highest risk of poor outcome (odds ratio, 5.5; 95% confidence interval, 1.2 to 24; P =0.01). In Kaplan-Meier analysis, patients who were anti-PLA2R1 <superscript>+</superscript> /anti-SOD2 <superscript>+</superscript> or anti-PLA2R1 <superscript>+</superscript> /anti-α-enolase <superscript>+</superscript> had lower eGFR at 12 months compared with patients who were anti-PLA2R1 <superscript>+</superscript> /anti-SOD2 <superscript>-</superscript> or anti-α-enolase <superscript>-</superscript> . Predictive tests (net reclassification index and area under the curve-receiver-operating characteristic analysis) showed that combined assessment of antibodies improved classification of outcome in 22%-34% of cases for partial remission of proteinuria and maintenance of normal eGFR. For patients with nephrotic syndrome at diagnosis, anti-SOD2 positivity and high anti-PLA2R1 titer were associated with a lack of complete remission. Patients who were anti-PLA2R1 <superscript>-</superscript> /anti-intracellular antigens <superscript>-</superscript> had the lowest proteinuria and the highest eGFR at diagnosis and the lowest risk of lower eGFR at 12 months. Epitope spreading was present in 81% of patients who were anti-PLA2R1 <superscript>+</superscript> and was associated with increased positivity for intracellular antigens and poor eGFR at diagnosis and 12 months.<br />Conclusions: Combined serological analysis of autoantibodies targeting membrane-bound and intracellular autoantigens identifies patients with poor clinical outcomes.<br /> (Copyright © 2020 by the American Society of Nephrology.)
- Subjects :
- Adult
Aged
Biomarkers blood
Cross-Sectional Studies
Female
France
Glomerulonephritis, Membranous blood
Glomerulonephritis, Membranous diagnosis
Glomerulonephritis, Membranous therapy
Humans
Italy
Male
Middle Aged
Predictive Value of Tests
Prognosis
Retrospective Studies
Serologic Tests
Time Factors
Aldehyde Reductase immunology
Autoantibodies blood
Biomarkers, Tumor immunology
DNA-Binding Proteins immunology
Glomerulonephritis, Membranous immunology
Phosphopyruvate Hydratase immunology
Receptors, Phospholipase A2 immunology
Superoxide Dismutase immunology
Thrombospondins immunology
Tumor Suppressor Proteins immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1555-905X
- Volume :
- 15
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Clinical journal of the American Society of Nephrology : CJASN
- Publication Type :
- Academic Journal
- Accession number :
- 33257410
- Full Text :
- https://doi.org/10.2215/CJN.02500220