NLRP1 mutations cause autoinflammatory diseases in human

Introduction Inflammation is a vital and complex process in response to diverse tissue damaging stimuli such as trauma, injury and pathogen. NLRP1, NLRP3 and NLRC4 belonging to the intracellular proteins Nod like receptor family, are capable of sensing the inflammatory inducers and trigger the assembly of a large complex called the inflammasome. By inducing the caspase-1 activation, inflammasome plays a crucial role in the release of IL-1b and IL-18, two critical cytokines of the initial steps of inflammatory responsesand, in some cases, the induction of a pro-inflammatory cell death called pyroptosis. Whereas mutations in NLRP3 and NLRC4 have been linked to two rare monogenic systemic autoinflammatory diseases (SAIDs), several polymorphisms in the NLRP1 gene have been associated extensively to an increased risk of autoimmune disorders (e.g. vitiligo, psoriasis, type 1 diabetes, and rheumatoid arthritis). We identified for the first time two distinct NLRP1 mutations in patients displaying a novel systemic autoinflammatory disease (SAID) and a novel syndrome combining autoinflammation and autoimmunity.