Evidence is emerging that failure to regulate immune cell cycle checkpoints such as PD-1/PD-L1 and CTLA-4 pathways, combined with abnormal expression of miRNAs targeting genes involved in T cell and B cell regulation, contributes to the loss of immune tolerance.[22] Moreover, epigenetic influences, including DNA methylation and histone modifications, affect gene expression in immune cells and are likely to account for the environment–gene interactions associated with autoimmunity in ITP. This evidence concerns the gene CTLA4 and autoimmune thrombocytopenic purpura.