Although many cytokines elevated in DS have well demonstrated pathogenic roles in the etiology of autoimmune diseases in the general population (e.g., TNF-α, IL6), their consistent upregulation in DS regardless of clinical evidence of autoimmune pathology indicates the existence of a prolonged pre-clinical period, where the hypercytokinemia likely precedes evident tissue damage and symptomology. The gene discussed is TNF; the disease is autoimmune disease.