While a relatively small study suggested that patients with previous immune diseases are less likely to develop SAE [(92)], in patients suffering from rheumatoid arthritis (RA), an autoimmune disease characterized by a higher state of inflammation, extracellular HMGB1 is known to be responsible for stimulating pro-inflammatory cytokine release (namely TNF and IL-1) [134]. This evidence concerns the gene TNF and rheumatoid arthritis.