Wheat-free Diet in the Treatment of Sjogren's Syndrome

In recent years, the existence of a wheat‐related disorder, in patients who do not sufferfrom celiac disease (CD) or wheat allergy (WA), has been definitively ascertained anddefined as non‐celiac wheat sensitivity (NCWS). Its prevalence in the general populationis unknown but self‐reported NCWS is around 10%. Conflicting data have been reportedabout the underlying physiopathology. It has been known for years how exposure togliadin, both in CD and in healthy patients (albeit with reduced levels in the latter),is able to alter intestinal permeability acting on zonulin release and signallingmechanisms. More recently, it has been shown that wheat has high concentrations of wheatamylase‐trypsin inhibitors (ATIs), proteins able to activate innate immunity viatoll‐like receptor‐4 (TLR‐4) on myeloid cells. Orally ingested ATIs increase intestinalinflammation by activating gut and mesenteric lymphnode myeloid cells.An increasing number of data have shown that patients with NCWS could have an associationwith autoimmune diseases, including thyroiditis, undifferentiated connective tissuedisease, psoriatic arthritis, spondylarthritis, and Sjogren's syndrome (SS).SS is an autoimmune disease characterized by an infiltrate of mononuclear cells, mainlylymphocytes, in the exocrine glands, especially the salivary and lacrimal glands. Somepreliminary data suggested that a GFD can reduce sialadenitis and increase salivary flowin SS and CD patients. Furthermore, some SS patients have an inflammatory response(release of nitric oxide) to a rectal gluten challenge.Based on these evidences, as well as on the ability of gluten/wheat to increaseintestinal permeability, altering zonulin mechanisms of regulation and signalling, andthe ability of some of its components (ATIs, but not only) to activate a localinflammatory response, it could be hypothesized that gluten/wheat may represents one ofthe pathogenetic environmental factors of SS and that its intake may be able to worsensymptoms in affected patients. In our hypothesis, exposure to gluten/wheat would cause arelease of zonulin, which, binding to the surface of the intestinal epithelial cells, isable to modify cell cytoskeleton and to cause the loss of normal occludins function,ultimately leading to an increased monolayer permeability. This increase in permeabilitywould result in greater exposure of the immune system cells to gluten/wheat molecules viaactivation of TLR‐4, with an increase in the infiltration and activation of myeloid cellsin the intestinal mucosa and an augmented activity of lymphnode dendritic cells. Suchlocal inflammatory response would have systemic repercussions with alteration of normalcytokine pattern and infiltration of monocytes/macrophages and T cells in the salivaryand lacrimal glands, thus being able to contribute, as an environmental factor, to theonset and exacerbation of the clinical manifestations of SS.Therefore, the investigators hypothesize that a wheat‐free diet (WFD) can reduce theinflammatory state and ameliorate the clinical symptoms in SS patients. This hypothesiswill be evaluated in both SS patients with associate GI symptoms and in those without GIsymptoms. The successive clinical and immunologic reaction to the re‐exposure to wheatingestion, performed by an open challenge, will be also evaluated to confirm awheat‐dependent mechanism and to understand the underlining mechanisms. The projectresults will provide data about a possible therapeutic role of a WFD in SS and willimprove the knowledges about the axis between the intestinal permeability and thesystemic inflammation in SS.More specifically, the investigators aim to: ‐ identify the prevalence of self‐reported NCWS in SS patients; ‐ assess the overall effect that a WFD plus cow's milk products free diet (CMPFD)determines in symptoms control of the patients affected with SS; the investigatorsdecided to include a CMPFD in association with a WFD because, according to severalauthors, including our previous studies, NCWS, and more generally gluten‐relateddisorders, are often associated with multiple foods intolerance, first of all cow'smilk products intolerance; ‐ evaluate, by an open wheat challenge, the real frequency of a coexistent NCWScondition; ‐ assess the possible role played by wheat ingestion in the pathogenesis and molecularmechanisms of SS and NCWS by analysing the variation of intestinal permeability andgut microbiota, in association with cytokines and lymphocytes pattern typical of SS.