Aberrant Methylated DNA Regions Lead to Low Activation of CD4+ T Cells with a Consequent Imbalance of the Th1/Th2 Polarization in IgA Nephropathy Patients

To investigate alterations in the DNA methylation of CD4+ T cells in IgA nephropathy (IgAN), we performed an initial whole-genome DNA methylation screening on CD4+ T cells isolated from 6 IgAN patients and 6 healthy subjects (HS). We analyzed more than 485000 CpGs targeted across their promoters, 5'-untranslated regions (UTRs), first exons, gene bodies and 3'UTRs. Some of the most significant differentially methylated regions included genes specifically expressed in T cells and involved in the T cell receptor signaling. In particular, we found hypomethylation in the promoter region of DUSP3 and in the 3’UTR of TRIM27 (chr17:41840001-41845000; ∆β= -0.39; chr6:28876508-28893266; ∆β= -0.31). The products of these genes function as signal transductors of the T cell receptor. Moreover, in the chromosome 5 (chr5:135416205-135416475) we found the most strongly and extensively hypermethylated region in IgAN patients respect to HS (∆β=0.31) in the promoter region of VTRNA2-1 gene (known as precursor microRNA miR-886). The methylated region, 200 bp upstream of the transcription start site, it is also part of a CpG island. Bisulfite-converted DNA from the 12 samples (CD4+ T cells from 6 IgAN patients and 6 healthy subjects) were hybridised to the Illumina Infinium HumanMethylation450 BeadChip.