title: A panel of serum biomarkers differentiates IgA nephropathy from other renal diseases.
abstract: OBJECTIVE
  There is increasing evidence that galactose-deficient IgA1 (Gd-IgA1) and Gd-IgA1-containing immune complexes are important for the pathogenesis of IgA nephropathy (IgAN). In the present study, we assessed a novel noninvasive multi-biomarker approach in the diagnostic test for IgAN.
  
  
  METHODS
  We compared serum levels of IgA, IgG, Gd-IgA1, Gd-IgA1-specific IgG and Gd-IgA1-specific IgA in 135 IgAN patients, 79 patients with non-IgAN chronic kidney disease (CKD) controls and 106 healthy controls. Serum was collected at the time of kidney biopsy from all IgAN and CKD patients.
  
  
  RESULTS
  Each serum marker was significantly elevated in IgAN patients compared to CKD (P<0.001) and healthy controls (P<0.001). While 41% of IgAN patients had elevated serum Gd-IgA1 levels, 91% of these patients exhibited Gd-IgA1-specific IgG levels above the 90th percentile for healthy controls (sensitivity 89%, specificity 92%). Although up to 25% of CKD controls, particularly those with immune-mediated glomerular diseases including lupus nephritis, also had elevated serum levels of Gd-IgA1-specific IgG, most IgAN patients had elevated levels of Gd-IgA1-specific antibody of both isotypes. Serum levels of Gd-IgA1-specific IgG were associated with renal histological grading. Furthermore, there was a trend toward higher serum levels of Gd-IgA1-specific IgG in IgAN patients with at least moderate proteinuria (≥1.0 g/g), compared to patients with less proteinuria.
  
  
  CONCLUSIONS
  Serum levels of Gd-IgA1-specific antibodies are elevated in most IgAN patients, and their assessment, together with serum levels of Gd-IgA1, improves the specificity of the assays. Our observations suggest that a panel of serum biomarkers may be helpful in differentiating IgAN from other glomerular diseases.
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Juntendo University Faculty of Medicine, Tokyo, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yanagawa
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Juntendo University Faculty of Medicine, Tokyo, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Suzuki
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Juntendo University Faculty of Medicine, Tokyo, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Suzuki
authors.affiliation: Division of Nephrology, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York, United States of America.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Kiryluk
authors.affiliation: Division of Nephrology, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York, United States of America.
authors.forename: Ali G
authors.initials: AG
authors.lastname: Gharavi
authors.affiliation: Clinical Research Center, Juntendo University Faculty of Medicine, Tokyo, Japan.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Matsuoka
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Juntendo University Faculty of Medicine, Tokyo, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Makita
authors.affiliation: Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, United States of America; Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Julian
authors.affiliation: Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
authors.forename: Jan
authors.initials: J
authors.lastname: Novak
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Juntendo University Faculty of Medicine, Tokyo, Japan.
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Tomino
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D003430:Cross-Sectional Studies; D003937:Diagnosis, Differential; D005260:Female; D005690:Galactose / Q000378:metabolism; D005922:Glomerulonephritis, IGA / Q000097:blood* / Q000175:diagnosis*; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood / Q000378:metabolism; D007074:Immunoglobulin G / Q000097:blood; D008297:Male; D008875:Middle Aged
chemical_list: D015415:Biomarkers; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D005690:Galactose