Some studies comparing immune responses in CD patients and NCWS patients indicate increased activity of the innate immune system, as seen in the Toll-like receptor 2, claudin-4, interleukin-8, and tumour necrosis factor alpha.53,54 This would indicate that the innate immune system plays a larger role in NCWS compared to CD, where the adaptive immune system plays a larger role.53,54 In fact, the very definition of NCWS as a distinct disease has been called into question due to its overlap with irritable bowel syndrome (IBS). Here, CLDN4 is linked to irritable bowel syndrome.