In a retrospective international study, circulating MIR-148b and let-7b were found to be serum markers for detecting primary IgA nephropathy

Grazia Serino, Francesco Pesce, Fabio Sallustio, Giuseppe De Palma, Sharon N. Cox, Claudia Curci, Gianluigi Zaza, Kar N. Lai, Joseph C.K. Leung, Sydney C.W. Tang, Aikaterini Papagianni, Maria Stangou, Dimitrios Goumenos, Miltiadis Gerolymos, Kazuo Takahashi, Yukio Yuzawa, Shoichi Maruyama, Enyu Imai, Francesco P. Schena

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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.

Original languageEnglish
Pages (from-to)683-692
Number of pages10
JournalKidney International
Volume89
Issue number3
DOIs
Publication statusPublished - 01-03-2016

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IGA Glomerulonephritis
Immunoglobulin A
Retrospective Studies
Biomarkers
MicroRNAs
Area Under Curve
Glomerular Mesangium
Validation Studies
Glomerulonephritis
Blood Donors
Serum
Galactose
Glycosylation
ROC Curve
Multicenter Studies
Kidney
Biopsy

All Science Journal Classification (ASJC) codes

  • Nephrology

Cite this

Serino, Grazia ; Pesce, Francesco ; Sallustio, Fabio ; De Palma, Giuseppe ; Cox, Sharon N. ; Curci, Claudia ; Zaza, Gianluigi ; Lai, Kar N. ; Leung, Joseph C.K. ; Tang, Sydney C.W. ; Papagianni, Aikaterini ; Stangou, Maria ; Goumenos, Dimitrios ; Gerolymos, Miltiadis ; Takahashi, Kazuo ; Yuzawa, Yukio ; Maruyama, Shoichi ; Imai, Enyu ; Schena, Francesco P. / In a retrospective international study, circulating MIR-148b and let-7b were found to be serum markers for detecting primary IgA nephropathy. In: Kidney International. 2016 ; Vol. 89, No. 3. pp. 683-692.
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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.",
author = "Grazia Serino and Francesco Pesce and Fabio Sallustio and {De Palma}, Giuseppe and Cox, {Sharon N.} and Claudia Curci and Gianluigi Zaza and Lai, {Kar N.} and Leung, {Joseph C.K.} and Tang, {Sydney C.W.} and Aikaterini Papagianni and Maria Stangou and Dimitrios Goumenos and Miltiadis Gerolymos and Kazuo Takahashi and Yukio Yuzawa and Shoichi Maruyama and Enyu Imai and Schena, {Francesco P.}",
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Serino, G, Pesce, F, Sallustio, F, De Palma, G, Cox, SN, Curci, C, Zaza, G, Lai, KN, Leung, JCK, Tang, SCW, Papagianni, A, Stangou, M, Goumenos, D, Gerolymos, M, Takahashi, K, Yuzawa, Y, Maruyama, S, Imai, E & Schena, FP 2016, 'In a retrospective international study, circulating MIR-148b and let-7b were found to be serum markers for detecting primary IgA nephropathy', Kidney International, vol. 89, no. 3, pp. 683-692. https://doi.org/10.1038/ki.2015.333

In a retrospective international study, circulating MIR-148b and let-7b were found to be serum markers for detecting primary IgA nephropathy. / Serino, Grazia; Pesce, Francesco; Sallustio, Fabio; De Palma, Giuseppe; Cox, Sharon N.; Curci, Claudia; Zaza, Gianluigi; Lai, Kar N.; Leung, Joseph C.K.; Tang, Sydney C.W.; Papagianni, Aikaterini; Stangou, Maria; Goumenos, Dimitrios; Gerolymos, Miltiadis; Takahashi, Kazuo; Yuzawa, Yukio; Maruyama, Shoichi; Imai, Enyu; Schena, Francesco P.

In: Kidney International, Vol. 89, No. 3, 01.03.2016, p. 683-692.

Research output: Contribution to journalArticle

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T1 - In a retrospective international study, circulating MIR-148b and let-7b were found to be serum markers for detecting primary IgA nephropathy

AU - Serino, Grazia

AU - Pesce, Francesco

AU - Sallustio, Fabio

AU - De Palma, Giuseppe

AU - Cox, Sharon N.

AU - Curci, Claudia

AU - Zaza, Gianluigi

AU - Lai, Kar N.

AU - Leung, Joseph C.K.

AU - Tang, Sydney C.W.

AU - Papagianni, Aikaterini

AU - Stangou, Maria

AU - Goumenos, Dimitrios

AU - Gerolymos, Miltiadis

AU - Takahashi, Kazuo

AU - Yuzawa, Yukio

AU - Maruyama, Shoichi

AU - Imai, Enyu

AU - Schena, Francesco P.

PY - 2016/3/1

Y1 - 2016/3/1

N2 - 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.

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