RCD [refractory CD (coeliac disease)] is characterized by severe symptoms/signs of malabsorption and mucosal damage unresponsive to a GFD (gluten-free diet). The pathogenesis of RCD is not fully understood. In the present paper, we have characterized the mucosal profile of effector cytokines in RCD. Duodenal biopsies were taken from patients with RCD, patients with active CD and normal controls and were analysed for inflammatory cytokines by real-time PCR and ELISA. IFN (interferon)-γ and IL (interleukin)-21 transcripts were increased in active CD patients but not in RCD patients as compared with normal controls, whereas IL-17A RNA was up-regulated in both active CD and RCD. No significant increase in IL-15 transcripts was observed in both active CD and RCD, whereas IL-15 protein was increased in active CD. IL-6 and TNF (tumour necrosis factor)-α were up-regulated only in RCD. As a proof, we present the case of a woman affected by RCD who responded to anti-TNF-α treatment with improvement of malabsorptive symptoms/signs but no healing of mucosal lesions. The findings indicate that the profile of mucosal effector cytokines differs between RCD and active CD and suggest that TNF-α, IL-6 and IL-17A, but not Th1-type cytokines, could drive the detrimental response in this condition.

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