and S.M.; writingreview and editing, B.L. articles met the inclusion criteria. In total, 50 patients with both CD and CAIT and 45 controls were reported. The effects of a GFD around the thyroid hormonal and immunological profile could be extracted only in a part of the studies. Two studies were case NKY 80 reports. A low risk of bias was observed. These findings advise further studies, ideally randomized, in order to better investigate the potential relationship between GFD and thyroid homeostasis. The level of evidence is not still sufficient to recommend GFD to patients with CAIT. 0.001; mean of three different determinations with standard deviations). A control group was present in two studies. The controls used in the study by Krysiak NKY 80 [15] were woman aged between 20 and 45 years old with recently diagnosed and previously untreated autoimmune thyroiditis (i.e., with positive TPO-Ab, reduced echogenicity of the thyroid parenchyma on thyroid ultrasonography, and normal thyroid function), who were incidentally found to be positive for anti-tissue transglutaminase antibodies without clinical symptoms of CD. Importantly, the group encompassed patients who preferred to follow a gluten-containing diet. In the study by Metso [14], the control subjects were collected from patients of the outpatient clinic. They were suffering from cardiovascular disorders (hypertension, arrhythmia, or a suspicion of coronary artery disease), did not have clinical evidence of CD, and were following a gluten-containing diet. 3.3. Quality Assessment The quality assessment of the studies is usually reported in Table 3. As a result of our rigorous selection criteria, a low risk of bias was recorded in all of the studies. Table 3 Quality assessment of the studies according to QUADAS-2. thead th align=”center” valign=”middle” style=”border-top:solid thin;border-bottom:solid thin” rowspan=”1″ colspan=”1″ /th th colspan=”4″ align=”center” valign=”middle” style=”border-top:solid thin;border-bottom:solid thin” rowspan=”1″ Risk of Bias /th th colspan=”3″ align=”center” valign=”middle” style=”border-top:solid thin;border-bottom:solid thin” rowspan=”1″ Feasibility /th th align=”center” valign=”middle” style=”border-bottom:solid thin” rowspan=”1″ colspan=”1″ First Author /th th align=”center” valign=”middle” style=”border-bottom:solid thin” rowspan=”1″ colspan=”1″ Patients Selection /th th align=”center” valign=”middle” style=”border-bottom:solid thin” rowspan=”1″ colspan=”1″ Index Test /th th align=”center” valign=”middle” style=”border-bottom:solid thin” rowspan=”1″ colspan=”1″ Reference Standard /th th align=”center” valign=”middle” style=”border-bottom:solid thin” rowspan=”1″ colspan=”1″ Flow and Timing /th th align=”center” valign=”middle” style=”border-bottom:solid thin” rowspan=”1″ colspan=”1″ Patients Selection /th th align=”center” valign=”middle” style=”border-bottom:solid thin” rowspan=”1″ colspan=”1″ Index Test /th th align=”center” valign=”middle” style=”border-bottom:solid thin” rowspan=”1″ colspan=”1″ Reference Standard /th /thead KrysiakLowLowLowLowLowLowLowMetsoLowUnclearLowLowLowLowLowMainardiLowUnclearUnclearLowLowUnclearLowValentinoHighUnclearUnclearLowLowUnclearLow Open in a separate window The studies by Asamoah [16] and Stramazzo [18] are not included in this quality assessment as they are NKY 80 a case report and letter to editor, respectively. 4. Discussion The present systematic review was conceived to achieve evidence-based information about the improvement of serum TSH and T-Ab levels in CD patients when they follow a GFD. As the association between CAIT and CD is usually recognized, and considering the overall worldwide prevalence of CAIT, our study should have a significant impact in clinical practice. Gluten is usually a molecule formed by glutenin polymers and gliadin monomers; both these proteins contain a high percentage of prolines and glutamines that safeguard them from complete degradation and digestion in the gastrointestinal tract [20]. In patients with CD, these gluten peptides trigger an inflammatory reaction also featured by the increased permeability of the intestinal barrier, a condition known as leaky gut [21]. This condition has been detected in several non-celiac autoimmune disorders, such as type 1 diabetes, Hashimotos thyroiditis, rheumatoid arthritis, and multiple sclerosis, to name but a few [22]. The increased permeability of the intestinal barrier may allow for the entrance of exogen compounds into systemic circulation [23]. Furthermore, it has been observed that gluten ingestion may affect gut microbiota composition [24], leading to a dysbiotic state that may enhance a vicious circle of gut epithelium damage; chronic inflammation; and, in people with a genetic predisposing background, autoimmunity [25]. Several studies in vitro and in animal models have hypothesized that gluten may impact key actions that may trigger autoimmunity, impairing both innate and/or adaptive immune branches. In non-obese diabetic (NOD) mice that are highly prone to spontaneously developing autoimmune disorders, a reduced expression and cytotoxicity of natural-killer cells toward a pancreatic beta cell line has been exhibited Alarelin Acetate [26]. Concerning the proinflammatory Th17 pathway, it appears to be increased in pancreatic lymph nodes of gluten-fed mice, but reduced in animals fed a gluten-free diet [27]. GFD exerts an anti-diabetic effect in the NOD murine model [28]. The literature about a possible positive effect of GFD on autoimmune disorders other than CD in human beings is large, but shows discrepant results. For example, a recent study on patients with concomitant CD and potential/subclinical pituitary autoimmunity suggests that GFD might be able to induce the remission of subclinical lymphocytic hypophysitis, or even prevent progression to a clinical stage [29]. On the other hand, a.