GENETICS

Le résumé fourni par la source

Introduction and Aims: Immunoglobulin A Nephropathy (IgAN) is the most common form of primary glomerulonephritis worldwide characterized by aberrant O-glycosylation in the hinge region of IgA1 (Gd-IgA1). A kidney biopsy for the diagnosis is required. Development of non-invasive tests for diagnosing the disease is needed. Methods: Two miRNAs (let-7b and miR-148b), previously identified by our group as regulators of the O-glycosylation process of IgA1, were measured by real-time quantitative PCR in serum samples recruited from the NIDIGAN study in which 88 Caucasian and 88 Asian biopsy-proven IgAN patients were matched with 102 Caucasian and 97 Asian healthy blood donors (HBD). We used the receiver operating characteristic (ROC) curve analysis to assess the diagnostic accuracy. Results: Training study. The mean serum levels of the combined miRNA biomarker were significantly higher in the Italian cohort of 50 IgAN patients when compared with 62 HBD (p < 0.0001) and in the Hong-Kong cohort (50 patients vs 50 HBD) (p < 0.0001). The areas under curve (AUC) were 0.91 (95% CI 0.8497-0.9589) for the Italian and 0.85 (95% CI 0.7709-0.9255) for the Hong-Kong cohort, respectively.Validation study. The mean serum levels were significantly higher in the Greek cohort of 38 IgAN patients when compared with 49 HBD (p < 0.0001) and in Japanese cohort (38 patients vs 47 HBD) (p < 0.0001). The AUC were 0.83 (95% CI 0.7260-0.9325) for the Greek and 0.75 (95% CI 0.6455-0.8567) for the Japanese cohort, respectively. Test study. Raised serum concentrations of the combined biomarker differentiated 16 IgAN patients from 13 non-IgAN patients and 16 HBD in Caucasians and Asian populations confirming the results obtained in the training and validation studies.Interestingly, the use of a linear regression model obtained by the bootstrap resampling methods showed that the diagnostic accuracy for IgAN versus all controls improved when both miRNAs and Gd-IgA1 values were considered. The AUC were 0.96 for Italian, 0.87 for Hong-Kong, 0.90 for Greek and 0.86 for Japanese IgAN patients. Conclusions: The combined miRNA biomarker (let-7b and miR-148b) appears to be the first robust non-invasive test for diagnosis of idiopatic IgAN.

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