title: In a retrospective international study, circulating miR-148b and let-7b were found to be serum markers for detecting primary IgA nephropathy.
abstract: Immunoglobulin A nephropathy (IgAN) is a worldwide disease characterized by the presence of galactose-deficient IgA1 deposits in the glomerular mesangium. A kidney biopsy for diagnosis is required. Here, we measured two miRNAs (let-7b and miR-148b), previously identified as regulators of the O-glycosylation process of IgA1, in serum samples from patients with IgAN and healthy blood donors (controls) recruited in an international multicenter study. Two predictive models, based on these miRNAs, were developed and the diagnostic accuracy of the combined biomarkers was assessed by the area under the receiver operating characteristic (ROC) curve (AUC) carried out in three steps. In a training study, the combined miRNAs were able to discriminate between 100 patients with IgAN and 119 controls (AUC, 0.82). A validation study confirmed the model in an independent cohort of 145 patients with IgAN and 64 controls (AUC, 0.78). Finally, in a test study, the combined biomarkers were able to discriminate patients with IgAN from 105 patients affected by other forms of primary glomerulonephritis, supporting the specificity (AUC, 0.76). Using the same study design, we also performed two subgroup analyses (one for Caucasians and one for East Asians) and found that race-specific models were the best fit to distinguish IgAN patients from controls. Thus, serum levels of the combined miRNA biomarker, let-7b and miR-148b, appears to be a novel, reliable, and noninvasive test to predict the probability of having IgAN.
authors.forename: Grazia
authors.initials: G
authors.lastname: Serino
authors.forename: Francesco
authors.initials: F
authors.lastname: Pesce
authors.forename: Fabio
authors.initials: F
authors.lastname: Sallustio
authors.forename: Giuseppe
authors.initials: G
authors.lastname: De Palma
authors.forename: Sharon N
authors.initials: SN
authors.lastname: Cox
authors.forename: Claudia
authors.initials: C
authors.lastname: Curci
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Zaza
authors.forename: Kar N
authors.initials: KN
authors.lastname: Lai
authors.forename: Joseph C K
authors.initials: JC
authors.lastname: Leung
authors.forename: Sydney C W
authors.initials: SC
authors.lastname: Tang
authors.forename: Aikaterini
authors.initials: A
authors.lastname: Papagianni
authors.forename: Maria
authors.initials: M
authors.lastname: Stangou
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Goumenos
authors.forename: Miltiadis
authors.initials: M
authors.lastname: Gerolymos
authors.forename: Kazuo
authors.initials: K
authors.lastname: Takahashi
authors.forename: Yukio
authors.initials: Y
authors.lastname: Yuzawa
authors.forename: Shoichi
authors.initials: S
authors.lastname: Maruyama
authors.forename: Enyu
authors.initials: E
authors.lastname: Imai
authors.forename: Francesco P
authors.initials: FP
authors.lastname: Schena
mesh_terms: D000328:Adult; D019540:Area Under Curve; D044466:Asian People / Q000235:genetics; D005260:Female; D005819:Genetic Markers; D005922:Glomerulonephritis, IGA / Q000097:blood* / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics; D006115:Greece / Q000453:epidemiology; D006723:Hong Kong / Q000453:epidemiology; D006801:Humans; D007558:Italy / Q000453:epidemiology; D007564:Japan / Q000453:epidemiology; D008297:Male; D035683:MicroRNAs / Q000097:blood* / Q000235:genetics; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D012372:ROC Curve; D015203:Reproducibility of Results; D012189:Retrospective Studies; D044465:White People / Q000235:genetics
chemical_list: D005819:Genetic Markers; C550570:MIRN148 microRNA, human; D035683:MicroRNAs; C487931:mirnlet7 microRNA, human