The newly identified methylation profiling of refractory immune thrombocytopenia (ITP) could point towards potential therapeutic targets, according to a study recently published in BMC Medical Genomics.

“Given the altered DNA methylation profiling of ITP, our study provides new insights into its genetic mechanism and suggests candidate biomarkers for the diagnosis and treatment of ITP,” the authors wrote.

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This prospective observational study included 14 patients previously diagnosed with refractory ITP from a single center in China and 14 cross-matched healthy controls. The researchers randomly selected 4 patients and 4 controls to undergo genome-wide DNA methylome profiling analysis.

Overall, the investigators reported 742,791 different loci, with 19% located in CPG islands. Of these, 260 CPG sites were highly methylated. Most of them followed a distribution along the intergenic regions TSS200, TSS1500, 5’UTR, and first Exon. Moreover, 46.2% of the differentially methylated sites were hypermethylated, represented by 120 sites that corresponded to 72 genes. On the other hand, the hypomethylated sites constituted 53.8%, with a total of 140 sites regarding 64 genes.

Subsequent functional enrichment analysis demonstrated that the differently methylated genes play important roles in platelet activation, signal transduction, apoptosis homeostasis, and DNA methylation regulation.

Furthermore, mRNA expression of C1orf109, CASP9, and AMD1 greatly varied between individuals with ITP and controls.

“Accordingly, it was hypothesized that CASP9, C1orf109, and AMD1 might be harnessed as therapeutic targets and provide a rationale for early diagnosis and treatment in patients with primary refractory ITP,” the authors wrote.

For example, the expression of CASP9 is associated with its own promoter region hypermethylation. The ITP group showcased lower mRNA expression of CASP9 compared to the control group. This finding could explain the resultant apoptosis inhibition of CD4+ T cells that activate the cellular immune system.

The other 64% loci were in the open sea region, while the rest were in gene promoters and adjacent upstream and downstream regions.


Du H, Tang Q, Yang J, et al. Genome-wide DNA methylation profiling of CD4+ T lymphocytes identifies differentially methylated loci associated with adult primary refractory immune thrombocytopenia. BMC Med Genom. Published online June 8, 2023. doi:10.1186/s12920-023-01557-0