Transcriptomic Signatures in IgA Nephropathy: From Renal Tissue to Precision Risk Stratification

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Publicado en:International Journal of Molecular Sciences vol. 26, no. 20 (2025), p. 10055-10077
Autor Principal: Delrue Charlotte
Outros autores: Speeckaert, Marijn M
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MDPI AG
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100 1 |a Delrue Charlotte  |u Department of Nephrology, Ghent University Hospital, 9000 Ghent, Belgium; charlotte.delrue@ugent.be 
245 1 |a Transcriptomic Signatures in IgA Nephropathy: From Renal Tissue to Precision Risk Stratification 
260 |b MDPI AG  |c 2025 
513 |a Journal Article 
520 3 |a IgA nephropathy (IgAN) is the most prevalent type of primary glomerulonephritis, with heterogeneous clinical outcomes. Conventional prognostic factors, such as proteinuria, eGFR, and Oxford histologic classification, have poor sensitivity and specificity. Recently, transcriptomic profiling has been employed to provide insights into the molecular definition of IgAN and facilitate patient stratification in those at risk of disease progression. In this review, we summarize our current understanding of IgAN derived from bulk RNA sequencing, single-cell transcriptomics, spatial transcriptomics, and gene expression profiling to elucidate the molecular characteristics of IgAN. Bulk transcriptomics of glomerular and tubulointerstitial compartments highlighted consistently upregulated genes (e.g., CCL2, CXCL10, LCN2, HAVCR1, COL1A1) and altered pathways (e.g., NF-κB, TGF-β, JAK/STAT, and complement) that are associated with clinical decline. Single-cell and single-nucleus RNA-sequencing has also identified the value of pathogenic cell types and regulatory networks in mesangial cells, tubular epithelium, and immune infiltrates. Furthermore, noninvasive transcriptomic signatures developed from urine and blood may represent useful real-time surrogates of tissue activity. With the advent of integrated analyses and machine learning approaches, personalized risk models that outperform traditional metrics are now available. While challenges remain, particularly related to standardization, cohort size, and clinical deployment, transcriptomics is likely to revolutionize IgAN by providing early risk predictions and precision therapeutics. Unlike prior reviews, our work provides an integrative synthesis across bulk, single-cell, spatial, and noninvasive transcriptomics, linking molecular signatures directly to clinical translation in risk stratification and precision therapeutics. 
653 |a Tumor necrosis factor-TNF 
653 |a Ligands 
653 |a Gene expression 
653 |a Chemokines 
653 |a Immunoglobulins 
653 |a Kidneys 
653 |a Biopsy 
700 1 |a Speeckaert, Marijn M  |u Department of Nephrology, Ghent University Hospital, 9000 Ghent, Belgium; charlotte.delrue@ugent.be 
773 0 |t International Journal of Molecular Sciences  |g vol. 26, no. 20 (2025), p. 10055-10077 
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