Changes in DNA methylation in naïve T helper cells regulate the pathophysiological state in minimal-change nephrotic syndrome.

BACKGROUND: DNA methylation plays a crucial role in regulating transcription, and changes in DNA methylation affect gene expression and disease development. Minimal change nephrotic syndrome (MCNS) has been reported to involve immunological disturbances. Since the characteristic features of the disease include recurrent relapse and sex and age preference, the disease pathogenesis may be partly related to epigenetic changes. However, little is known about these changes.

METHODS: We analyzed genome-wide DNA methylation using the microarray-based integrated analysis of methylation by isoschizomers method. This method was used to evaluate methylation in monocytes (patient number; n = 6) and naïve T helper cells (n = 4) from the peripheral blood of MCNS patients both in relapse and following remission and that of healthy controls (n = 5).

RESULTS: In total, 85 co-occurring genes were identified in naïve T helper cells, while 4 such genes were identified in monocytes, which were common among the 3 following comparisons for changes in DNA methylation using sample pairs: (1) relapse versus remission, (2) relapse versus controls, and (3) remission versus controls. In 82 of 85 co-occurring genes (96.5%) in naïve T helper cells, the level of DNA methylation was altered according to disease activity, but was not related to disease activity in the 4 genes detected in monocytes.

CONCLUSIONS: Therefore, in 82 co-occurring genes in naïve T helper cells, the regulation of DNA methylation was well correlated with the clinical and pathophysiological state. Our genome-wide approach to analyze DNA methylation provides further insight into the pathogenesis of MCNS and indicates potential prediction and diagnostic tool for the disease.