Proof that the increased NLRP3 inflammasome-mediated production of IL-1β is the cause of Crohn's disease in these kindred comes from the fact that the proband had severe Crohn's disease that did not respond to anti-TNF-α administration but did respond to agents that block IL-1β activity (initially anakinra and later canakinumab) with the corresponding abdominal symptoms and decrease of fecal calprotectin titers. Here, TNF is linked to Crohn disease.