Abstract
KEY POINTS: Inflammation and immune response pathways were enriched in IgA nephropathy/IgA vasculitis with nephropathy compared with living donors. The transcriptomic profile differed significantly between adults and children with the disease. BACKGROUND: Disease manifestations and progression of IgA nephropathy vary widely between individuals, particularly between children and adults. To further understand these differences, we examined the transcriptional profiles in kidney biopsies from both adult and pediatric patients with IgA nephropathy or IgA vasculitis with nephropathy in relation to normal kidneys. METHODS: Kidney biopsies from 95 participants, 71 adults and 13 children with histopathologically verified IgA nephropathy or IgA vasculitis with nephropathy as well as 11 living donors, were microdissected into glomerular and tubulointerstitial fractions and subjected to RNA sequencing. Differential gene expression analysis was performed across groups, and functional enrichment analyses were conducted using gene ontology and Kyoto Encyclopedia of Genes and Genomes. Histopathological grading (Oxford and part of the Banff classifications) and clinical data (at time of biopsy and up to 5 years of follow-up) were analyzed in relation to normalized RNA counts. RESULTS: Differentially expressed genes obtained from all patients versus living donors, both glomerular and tubulointerstitial fractions, were enriched for immune system and complement activation pathways. When comparing adults with children within the IgA nephropathy/IgA vasculitis with nephropathy group, 5562 and 3539 differentially expressed genes in each fraction were identified, which were enriched in pathways related to the endoplasmic reticulum and mitochondrial activity (glomeruli), as well as T-cell activation (tubulointerstitium). CONCLUSIONS: Distinct transcriptional profiles with enrichment of inflammation and immune response pathways were revealed in patients compared with living donors. However, the transcriptomic signatures across adult and pediatric patients were not consistent, highlighting differences in pathways involved in endoplasmic reticular, mitochondrial, and T-cell activity. PODCAST: This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/JASN/2025_09_10_ASN0000000787.mp3