title: Protein microarrays discover angiotensinogen and PRKRIP1 as novel targets for autoantibodies in chronic renal disease.
abstract: Biomarkers for early detection of chronic kidney disease are needed, as millions of patients suffer from chronic diseases predisposing them to kidney failure. Protein microarrays may also hold utility in the discovery of auto-antibodies in other conditions not commonly considered auto-immune diseases. We hypothesized that proteins are released as a consequence of damage at a cellular level during end-organ damage from renal injury, not otherwise recognized as self-antigens, and an adaptive humoral immune response to these proteins might be detected in the blood, as a noninvasive tracker of this injury. The resultant antibodies (Ab) detected in the blood would serve as effective biomarkers for occult renal injury, enabling earlier clinical detection of chronic kidney disease than currently possible, because of the redundancy of the serum creatinine as a biomarker for early kidney injury. To screen for novel autoantibodies in chronic kidney disease, 24 protein microarrays were used to compare serum Ab from patients with chronic kidney disease against matched controls. From a panel of 38 antigens with increased Ab binding, four were validated in 71 individuals, with (n=50) and without (n=21) renal insufficiency. Significant elevations in the titer of novel auto-Ab were noted against angiotensinogen and PRKRIP1 in renal insufficiency. Current validation is underway to evaluate if these auto-Ab can provide means to follow the evolution of chronic kidney disease in patients with early stages of renal insufficiency, and if these rising titers of these auto-Ab correlate with the rate of progression of chronic kidney disease.
authors.affiliation: Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305, USA. abutte@stanford.edu
authors.forename: Atul J
authors.initials: AJ
authors.lastname: Butte
authors.forename: Tara K
authors.initials: TK
authors.lastname: Sigdel
authors.forename: Persis P
authors.initials: PP
authors.lastname: Wadia
authors.forename: David B
authors.initials: DB
authors.lastname: Miklos
authors.forename: Minnie M
authors.initials: MM
authors.lastname: Sarwal
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000808:Angiotensinogen / Q000276:immunology*; D000818:Animals; D001323:Autoantibodies / Q000276:immunology*; D002454:Cell Differentiation; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D007676:Kidney Failure, Chronic / Q000276:immunology*; D051379:Mice; D008969:Molecular Sequence Data; D010748:Phosphopeptides / Q000737:chemistry / Q000378:metabolism; D010750:Phosphoproteins / Q000737:chemistry / Q000378:metabolism; D010766:Phosphorylation; D040081:Protein Array Analysis / Q000379:methods*; D020543:Proteome / Q000737:chemistry / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D010748:Phosphopeptides; D010750:Phosphoproteins; C476452:Prkrip1 protein, mouse; D020543:Proteome; D016601:RNA-Binding Proteins; D000808:Angiotensinogen