title: Profiling of autoantibodies in IgA nephropathy, an integrative antibiomics approach.
abstract: OBJECTIVE
  IgG commonly co-exists with IgA in the glomerular mesangium of patients with IgA nephropathy (IgAN) with unclear clinical relevance. Autoantibody (autoAb) biomarkers to detect and track progression of IgAN are an unmet clinical need. The objective of the study was to identify IgA-specific autoAbs specific to IgAN.
  
  
  METHODS
  High-density protein microarrays were evaluated IgG autoAbs in the serum of IgAN patients (n = 22) and controls (n = 10). Clinical parameters, including annual GFR and urine protein measurements, were collected on all patients over 5 years. Bioinformatic data analysis was performed to select targets for further validation by immunohistochemistry (IHC).
  
  
  RESULTS
  One hundred seventeen (1.4%) specific antibodies were increased in IgAN. Among the most significant were the autoAb to the Ig family of proteins. IgAN-specific autoAbs (approximately 50%) were mounted against proteins predominantly expressed in glomeruli and tubules, and selected candidates were verified by IHC. Receiver operating characteristic analysis of our study demonstrated that IgG autoAb levels (matriline 2, ubiquitin-conjugating enzyme E2W, DEAD box protein, and protein kinase D1) might be used in combination with 24-hour proteinuria to improve prediction of the progression of IgAN (area under the curve = 0.86, P = 0.02).
  
  
  CONCLUSIONS
  IgAN is associated with elevated IgG autoAbs to multiple proteins in the kidney. This first analysis of the repertoire of autoAbs in IgAN identifies novel, immunogenic protein targets that are highly expressed in the kidney glomerulus and tubules that may bear relevance in the pathogenesis and progression of IgAN.
authors.affiliation: Departments of Pediatrics-Nephrology, Stanford University School of Medicine, Stanford, CA 94304, USA.
authors.forename: Tara K
authors.initials: TK
authors.lastname: Sigdel
authors.forename: Sang Hoon
authors.initials: SH
authors.lastname: Woo
authors.forename: Hong
authors.initials: H
authors.lastname: Dai
authors.forename: Purvesh
authors.initials: P
authors.lastname: Khatri
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Bryan
authors.initials: B
authors.lastname: Myers
authors.forename: Minnie M
authors.initials: MM
authors.lastname: Sarwal
authors.forename: Richard A
authors.initials: RA
authors.lastname: Lafayette
mesh_terms: D000328:Adult; D000918:Antibody Specificity; D001323:Autoantibodies / Q000097:blood*; D019295:Computational Biology; D005260:Female; D005919:Glomerular Filtration Rate; D005922:Glomerulonephritis, IGA / Q000276:immunology*; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007145:Immunoglobulin kappa-Chains / Q000032:analysis; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D011493:Protein Kinase C / Q000032:analysis; D044763:Ubiquitin-Conjugating Enzymes / Q000032:analysis
chemical_list: D001323:Autoantibodies; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007145:Immunoglobulin kappa-Chains; C510626:UBE2W protein, human; D044763:Ubiquitin-Conjugating Enzymes; C089212:protein kinase D; D011493:Protein Kinase C