Serum Levels of miR-148b and Let-7b at Diagnosis May Have Important Impact in the Response to Treatment and Long-Term Outcome in IgA Nephropathy

Abstract

Background/aims: Previous studies showed that two microRNAs, let-7b and miR-148, which regulate the O-glycosylation process of IgA1, may predict diagnosis of primary IgA nephropathy (IgAN). The combined analysis of their serum levels in calculated statistical models may act as serum biomarkers for the diagnosis of primary IgAN. In the present study, we aimed to assess their impact not only on clinical and histological findings at onset but also on renal function after a long-term follow-up. Patients and methods: We enrolled 61 Caucasian patients with biopsy-proven IgAN. Serum levels of miR-148b, let-7b, and galactose-deficient IgA1 (Gd-IgA1) at the time of diagnosis were measured using real-time quantitative PCR and enzyme-linked immunosorbent assay using the monoclonal antibody KM55, respectively. Their values along with calculated Models 1 and 2 were correlated with histologic scoring system (Oxford classification system) and with renal function at diagnosis and after 11.9 ± 6.6 years. Fifty-five healthy volunteers were enrolled as controls. Results: No significant correlation was found between miRNA and Gd-IgA1 levels and eGFR and proteinuria at diagnosis. A significant negative association was detected between the presence of crescents and serum levels of let-7b (p = 0.002), miR-148b (p = 0.01), and Models 1 and 2 (p = 0.02 and p = 0.007, respectively). At the end of follow-up, eGFR correlated with let-7b levels (p = 0.01), Model 1 (p = 0.002), and Model 2 (p = 0.004). Patients with fast progression of the renal damage had significantly increased levels of let-7b (p = 0.01), Model 1 (p = 0.003), and Model 2 (p = 0.005) compared to slow progressors, as did those who reached ESKD (p = 0.002, p = 0.001, and p = 0.001, respectively). Results were most prominent in those treated with corticosteroids. Finally, cut off levels in Models 1 and 2 could also predict the renal function outcome after long-term follow-up. Conclusions: Serum levels of let-7b and miR-148b and their combination, may serve as predictors for long-term renal function outcomes, particularly in patients treated with corticosteroids.

Integration of three machine learning algorithms identifies characteristic RNA binding proteins linked with diagnosis, immunity and pyroptosis of IgA nephropathy

“…Nevertheless, percutaneous renal biopsies are often not carried out, and proposed histological classifications (Oxford classification system, etc.) have a few shortcomings ( Kouri et al, 2021 ). As the undesirable clinical outcomes of patients with IgA nephropathy is in part the results of delayed diagnosis, reliable non-invasive biomarkers are urgently required, which could be applied to routine clinical practice ( Moresco et al, 2015 ).…”

Title IgA Nephropathy and Oral Bacterial Species Related to Dental Caries and Periodontitis

“…Another microRNA, miR-148b, can inhibit C1GALT1 [ 125 ] (see Figure 7 ). Moreover, serum levels of miR-148b and let-7b were related to the response to treatment and long-term outcome in IgAN [ 126 ]. The microRNA miR-196b can affect COSMC [ 127 ].…”

IgA vasculitis nephritis

“…In adults, urinary IgA levels at disease onset were associated with adverse course [55]. Promising results were also published for two microRNAs, let-7b and miR-148, in the prediction of long-term renal outcome [43]. Furthermore, following metabolomic analyses, choline and cis-vaccenic acid in serum and/or urine were suggested as potential markers to predict IgAVN progression [56].…”

“…Since aberrant glycosylation and galactosylation of IgA plays such a pivotal role in the disease, it is not surprising that altered expression of genes coding for proteins involved in glycosylation like glycoprotein-N-acetylgalactosamine 3-b-galactosyltransferase (C1GALT1), C1GALT1 Specific Chaperone 1 (C1GALTC1; COSMC) and N-acetylgalactosaminide a-2,6-sialyltransferase 2 (ST6GALNAC2) might be a predisposing factor [41,42]. Micro-RNAs that impact upon antibody glycosylation and receptor expression influence the course of the disease [15 ▪ ,38,43]. In addition, genes associated with the regulation of the innate immune system like MGAT5 (a negative regulator of T-cell activation thresholds) or Macrophage Migration Inhibitory Factor (MIF) seem to increase the susceptibility toward IgA vasculitis [44].…”