Journal Article

Galactose-deficient IgA1 and the corresponding IgG autoantibodies predict IgA nephropathy progression

Hall, Stacy, Reily, Colin, Brown, Rhubell, Honsova, Eva, Zima, Tomas, Novak, Jan, Tesar, Vladimir, Ling, Chunyan, Neprasova, Michaela, Suchanek, Miloslav, Maixnerova, Dita

2019

Overview

IgA nephropathy (IgAN), the most common primary glomerulonephritis worldwide, has serious outcomes with end-stage renal disease developing in 30-50% of patients. The diagnosis requires renal biopsy. Due to its inherent risks, non-invasive approaches are needed. We evaluated 91 Czech patients with biopsy-proven IgAN who were assessed at time of diagnosis for estimated glomerular filtration rate (eGFR), proteinuria, microscopic hematuria, and hypertension, and then followed prospectively. Serum samples collected at diagnosis were analyzed for galactose-deficient IgA1 (Gd-IgA1) using new native-IgA1 and established neuraminidase-treated-IgA1 tests, Gd-IgA1-specific IgG autoantibodies, discriminant analysis and logistic regression model assessed correlations with renal function and Oxford classification (MEST score). Serum levels of native (P <0.005) and neuraminidase-treated (P <0.005) Gd-IgA1 were associated with the rate of eGFR decline. A higher relative degree of galactose deficiency in native serum IgA1 predicted a faster eGFR decline and poor renal survival (P <0.005). However, Gd-IgA1 has not differentiated patients with low vs. high baseline eGFR. Furthermore, patients with high baseline eGFR that was maintained during follow-up were characterized by low serum levels of Gd-IgA1-specific IgG autoantibodies (P = 0.003). Including levels of native and neuraminidase-treated Gd-IgA1 and Gd-IgA1-specific autoantibodies at diagnosis may aid in the prognostication of disease progression in Czech patients with IgAN. Future tests will assess utility of these biomarkers in larger patients cohorts from geographically distinct areas.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Acids / Adult / Analysis / Antibodies / Autoantibodies / Autoantibodies - blood / Autoantibodies - immunology / Autoimmunity / Biological markers / Biology and Life Sciences / Biomarkers / Biomarkers - blood / Biopsy / Chronic kidney failure / Development and progression / Diagnosis / Discriminant analysis / Disease Progression / End-stage renal disease / Epidermal growth factor receptors / Exo-a-sialidase / Female / Follow-Up Studies / Gadolinium / Galactose / Galactose - blood / Galactose - immunology / Glomerular filtration rate / Glomerulonephritis / Glomerulonephritis, IGA - blood / Glomerulonephritis, IGA - diagnosis / Glomerulonephritis, IGA - immunology / Glomerulonephritis, IGA - mortality / Hematuria / Humans / Hypertension / Iga glomerulonephritis / IgA nephropathy / Immunoglobulin A / Immunoglobulin A - blood / Immunoglobulin A - immunology / Immunoglobulin G / Kidney diseases / Laboratories / Lectins / Male / Medicine / Medicine and Health Sciences / Nephrology / Outcome and process assessment (Medical care) / Patients / People and Places / Physical Sciences / Prognosis / Prospective Studies / Proteinuria / Regression analysis / Regression models / Renal function / Serum levels