MAS is a heterogenous syndrome encompassing different aetiologies; however, one type of MAS, NLR family CARD domain-containing protein 4 (NLRC-4) mutation-related, was discovered in 2018 to be pathologically driven [6] by loss of negative-feedback control of interleukin-18 (IL-18) due to failure of its binding protein (IL-18bp) production, resulting in elevated levels of the biologically active “free” IL-18 (fIL-18) component. This evidence concerns the gene NLRC4 and macrophage activation syndrome.