Mechanistically, smoking may contribute to MS progression through oxidative stress, nitric oxide-induced axonal degeneration, increased BBB permeability, and chronic immune activation.149,150 Additionally, epigenetic interactions with HLA genes further support the role of smoking in MS susceptibility, with smokers carrying HLA-DRB1*15 and lacking HLA-A02 facing a 13-fold increased risk.151. The gene discussed is HLA-DRB1; the disease is myeloid sarcoma.